Search

To investigate the changes in proinflammatory cytokines and chemokines, namely, C-C motif ligand (CCL) 2 and CCL7, in postmenopausal osteoporosis (PMOP) and to develop a new drug, bindarit (Bnd), for PMOP in an ovariectomized (OVX) mouse model.Bone marrow macrophages (BMMs) from the femurs of five women with PMOP and five premenopausal women without osteoporosis were detected by RNA sequencing. BMMs from mice were differentiated into osteoclasts and treated with a synthetic inhibitor of CCL2 and CCL7, Bnd, or 17 beta estradiol (ECCL2, CCL7 and their receptor of C-C chemokine receptor-2 (CCR2), and the NF-κB signaling pathway, were significantly increased in women with PMOP. CCL2 and CCL7 protein and mRNA expression was increased in OVX mice and aged female mice, but the increases were attenuated by EThe proinflammatory cytokines and chemokines CCL2, CCL7 and CCR2 were correlated with PMOP. Bnd attenuated the increases in CCL2 and CCL7 levels to affect osteoporosis in OVX mice via the NFκB signaling pathway. Thus, Bnd may be useful as a new therapeutic for the prevention of PMOP.

At the end of 2019 Wuhan witnessed an outbreak of “atypical pneumonia” that later developed into a global pandemic. Metagenomic sequencing rapidly revealed the causative agent of this outbreak to be a novel coronavirus denoted SARS-CoV-2. To provide a snapshot of the pathogens in pneumonia-associated respiratory samples from Wuhan prior to the emergence of SARS-CoV-2, we collected bronchoalveolar lavage fluid samples from 408 patients presenting with pneumonia and acute respiratory infections at the Central Hospital of Wuhan between 2016 and 2017. Unbiased total RNA sequencing was performed to reveal their “total infectome”, including viruses, bacteria and fungi. We identified 35 pathogen species, comprising 13 RNA viruses, 3 DNA viruses, 16 bacteria and 3 fungi, often at high abundance and including multiple co-infections (13.5%). SARS-CoV-2 was not present. These data depict a stable core infectome comprising common respiratory pathogens such as rhinoviruses and influenza viruses, an atypical respiratory virus (EV-D68), and a single case of a sporadic zoonotic pathogen–Chlamydia psittaci. Samples from patients experiencing respiratory disease on average had higher pathogen abundance than healthy controls. Phylogenetic analyses of individual pathogens revealed multiple origins and global transmission histories, highlighting the connectedness of the Wuhan population. This study provides a comprehensive overview of the pathogens associated with acute respiratory infections and pneumonia, which were more diverse and complex than obtained using targeted PCR or qPCR approaches. These data also suggest that SARS-CoV-2 or closely related viruses were absent from Wuhan in 2016–2017.

Bamboos are one of the fast-growing and multiple use species in the world, and thus bamboo forests/plantations play an important role in C sequestration at regional and global levels. We studied aboveground litterfall, litter decomposition and nutrient dynamics for two years in two subtropical bamboo ecosystems in Southwest China so as to test the hypothesis that litter quality determine the rate and nutrient dynamics during decomposition of different litter fractions. Mean annual total aboveground litter production ranged from 494 to 434 g m −2 in two bamboo stands (P stand, dominated by Pleioblastus amarus and H stand, hybrid bamboo dominated by Bambusa pervariabilis × Dendrocalamopsis daii ). Bulk (∼80%) of litter production was contributed by leaf litter in two stands followed by twigs and sheathes. Different litter fractions represented considerable variations in the rates of mass loss and nutrient release. Variation of the mass remaining after 2 years of decomposition was significantly explained by initial C/N ratio and initial P concentration. Initial concentrations of N, P, Ca, and Mg explained 57.9%, 95.0%, 99.8% and 98.1%, respectively, of the variations of these elements mass remaining after 2 years of decomposition. The patterns of nutrient dynamics and the final amount remaining were mainly determined by their initial litter substrate quality in these two subtropical bamboo plantations.

As an important component of the global carbon (C) budget, litter decomposition in terrestrial ecosystems is greatly affected by the increasing nitrogen (N) deposition observed globally. We hypothesized that different litter fractions derived from a single tree species may respond to N deposition differently depending on the quality of the litter substrate. To test the hypothesis, a two-year field experiment was conducted using the litterbag method in a Pleioblastus amarus plantation in the rainy region of Southwest China. Four N treatment levels were applied: control (no N added), low-N (50 kg N ha −1 year −1 ), medium-N (150 kg N ha −1 year −1 ), and high-N (300 kg N ha −1 year −1 ). We observed different patterns of mass loss for the three P. amarus litter fractions (leaves, sheaths, and twigs) of varying substrate quality in the control plots. There were two decomposition stages with different decay rates (fast rate in early stages and slow rate in the later stages) for leaves and sheaths, while we did not observe a slower phase for the decay of twigs during the 2-year study period. The annual decomposition rate ( k ) of twigs was significantly lower than that of leaves or sheaths. Addition of N slowed the decomposition of leaves and twigs in the later stages of decomposition by inhibiting the decay of lignin and cellulose, while addition of N did not affect the mass loss of sheaths during the study period. In the decomposition of all three litter fractions, experimental N deposition reduced the net N accumulation in the early stages and also decreased the net N release in the later stages. The results of this study suggest that litter substrate quality may be an important factor affecting litter decomposition in a bamboo ecosystem affected by N deposition.

Effects of decomposing leaf litter of Cinnamomum camphora on growth, physiological and phenological traits of Capsicum annuum, and modification of these effects by nitrogen application were investigated using a pot experiment. C. camphora leaf litter was applied at rate of 0, 25, 50 100 g per pot, resulting into four treatments, i.e., CK (the control), L25, L50, and L100. Nitrogen application was firstly performed on the 39th d of decomposition (3.0 g urea was added to each pot six times). Leaf area, plant height, basal diameter and biomass production of C. annuum were all inhibited sharply by exposure to the leaf litter, and the inhibition effect increased with the increasing leaf litter in terms of both the intensity and the stability. Treated with L25, budding number reduced by 88.7% averagely during 55th-75th d, and the rate of fructification plant decreased by 40% on the 96th d of decomposition, while neither buds nor fruits were observed when exposed to L50 and L100 at that time. Pigment contents and net photosynthetic rate (Pn) were impacted due to leaf litter addition, and malonaldehyde (MDA) was only markedly promoted by L100. Inhibition on growth and development of C. annuum caused by leaf litter decomposition could be alleviated by nitrogen application. Leaf area treated with leaf litter recovered to the control level on the 52nd d after nitrogen application, and similar results appeared on the 83rd d after nitrogen application for other growth traits. Budding and fructification status were also visibly improved.

As an important contributor to carbon (C) flux in the global C cycle, fine root litter decomposition in forests has the potential to be affected by the elevated nitrogen (N) deposition observed globally. From November 2007 to January 2013, a field experiment involving monthly simulated deposition of N in a Pleioblastus amarus plantation was conducted in the Rainy Area of West China. Four levels of nitrogen deposition were included as control (0 g N x m(-2) x a(-1)), low nitrogen (5 g N x m(-2) x a(-1)), medium nitrogen (15 g N x m(-2) x a(-1)) and high nitrogen (30 g N x m(-2) x a(-1)). After 3 years of simulated N deposition experiment (January 2011) , a two-year fine root decomposition experiment was conducted in the simulated N deposition plots using litterbag method, under monthly experimental N deposition. The decomposition rates of fine roots were fast first and then slow. Mass loss of fine roots in the first year of decomposition was up to 60%, and the change of the remaining mass was very slow in the second year. The time of 50% and 95% mass loss of fine roots was 1.20 and 5.17 years, respectively, under the conditions of no addition N input. In general, decomposition rates were underestimated using negative exponential model. Simulated N deposition significantly inhibited the decomposition of fine roots. The remaining mass in the high nitrogen treatment was 51.0% higher than that in the control, after two years of decomposition. Simulated N deposition increased C, P and K contents in the remaining mass of litter. Compared with the control, soil pH decreased significantly in the medium and high nitrogen treatments, soil organic C, total N, ammonium and nitrate contents and fine root biomass of P. amarus increased significantly in the high nitrogen treatment after simulated N deposition for 4. 5 years. Key words: nitrogen deposition; fine root decomposition; Pleioblastus amarus.

From March to May, 2010, a pot experiment was conducted to investigate the effects of Eucalyptus grandis leaf litter at its early stage of decomposition on the growth and photosynthetic characteristics of Cichorium intybus. Four treatments with different application rate of the leaf litter, i.e., 0 g x pot(-1) (CK), 30 g x pot(-1) (A1), 60 g x pot(-1) (A2), and 90 g x pot(-1) (A3), were installed. Each pot contained 12 kg soil mixed with the leaf litter, and then, C. intybus was sown. The growth indicators of the C. intybus were measured at the 30, 45, 60, and 75 d after sowing, and the photosynthetic characteristics of the C. intybus in treatment A3 were studied after the seedlings third leaf fully expanded. At each measured time, the biomass accumulation and leaf area growth of C. intybus in treatments A1, A2, and A3 were inhibited significantly. At the early stage of the leaf litter decomposition, the synthesis of photosynthetic pigments of the C. intybus seedlings was inhibited significantly, and the inhibition effect was getting stronger with the increasing amount of the leaf litter addition. The diurnal change of the seedlings photosynthetic rate in all treatments showed a bimodal curve with midday depression, the stomatal conductance and water use efficiency had the same variation trend with the net photosynthetic rate, and the total diurnal photosynthesis decreased in the order of CKA1A2A3. The GC-MS analysis showed there were 33 kinds of small molecule compounds released gradually with the decomposition of the leaf litter, among which, allelopathic substance terpenoid dominated.

From January 2008 to January 2009, a field experiment was conducted to investigate the effects of simulated nitrogen (N) deposition (0, 5, 15, and 30 g N x m(-2) x a(-1)) on the soil enzyme activities in a Betula luminifera plantation in Rainy Area of West China. As compared with the control (0 g N x m(-2) x a(-1)), simulated N deposition stimulated the activities of soil hydrolases (beta-fructofuranosidase, cellulase, acid phosphatase, and urease) significantly, but depressed the activities of soil oxidases (polyphenol oxidase and peroxidase). These results suggested that the increased exogenous inorganic N could stimulate soil microbial activity and increase the demands of both B. luminifera and soil microbes for C and P, whereas the depress of soil polyphenol oxidase and peroxidase activities under N addition could inhibit the degradation of litter and promote its accumulation in soil, leading to the increase of soil C storage in the B. luminifera plantation ecosystem.

A pot experiment was conducted to study the effects of Eucalyptus grandis leaf litter during its early stage decomposition on the growth and the photosynthesis of Cichorium intybus. Each pot contained 12 kg soil mixed with different amounts of E. grandis leaf litter (30 g x pot(-1), A1; 60 g x pot(-1), A2; 90 g x pot(-1), A3; and 0 g x pot(-1), CK), and sowed with C. intybus. The growth indicators and the photosynthetic characteristics of C. intybus were measured after the third leaf of C. intybus seedlings fully expanded in treatment A3. At the early stage of leaf litter decomposition, the C. intybus biomass accumulation, leaf area growth, and synthesis of photosynthetic pigments were inhibited significantly, and the inhibition effect was getting stronger with the increasing amount of the leaf litter addition. The intercellular CO2 concentration of C. intybus was increased by litter addition, while the net photosynthetic rate, stomatal conductance, and transpiration rate were significantly lower than those of the control. With the increase of leaf litter addition, all the parameters of C. intybus light response and CO2 response except CO2 compensation point showed an obvious downward trend, and there existed significant differences between the treatments of litter additions and the control. It was suggested that during the decomposition of E. grandis leaf litter, its allelopathic substances released gradually and acted on receptor plants, inhibited the synthesis of photosynthetic pigments and the photosynthesis of the receptors, decreased the receptors environmental adaptation ability, and accordingly, inhibited the growth of C. intybus.

Chronic hypoxia induces proliferation of human pulmonary artery smooth muscle cells (hPASMCs), leading to remodeling and pulmonary hypertension, but the mechanism remains unclear. The present study tested the roles of mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) and mitochondrial membrane potential (DeltaPsi(m)) on hPASMCs under normoxic or hypoxic conditions. Our results demonstrated that diazoxide or hypoxia, alone or in combination, could depolarize DeltaPsi(m) through opening mitoK(ATP), release of cytochrome C, and overproduction of hydrogen peroxide by mitochondria, resulting in increased proliferation and decreased apoptosis of hPASMCs. Five-hydroxydecanoate could partly reduce these hypoxia-dependent responses. These results suggest that the opening of mitoK(ATP) followed by a depolarization of DeltaPsi(m) might play an important role in hypoxic proliferation of hPASMCs through cytochrome C accumulation within the mitochondria or mitochondrial overproduction of hydrogen peroxide.

The objective of this paper was to investigate the effect and mechanism of mitochondrial ATP-sensitive K(+) (MitoK(ATP)) channel on the proliferation of airway smooth muscle cells (ASMCs) in asthmic rats. Thirty-six Sprague-Dawley (SD) rats were randomly assigned into 2 groups (18 in each): (1) Asthma group: the asthmic rat model was established by ovalbumin (OVA) sensitization and excitation; (2) Normal group: rats were subjected to inhalation of equal amount of normal saline. The rat ASMCs were isolated from fresh lung tissues and cultured respectively as follows: (1) CONTROL GROUP: normal ASMCs were cultured under normoxia for 24 h; (2) Diazoxide group: normal ASMCs were cultured under normoxia for 24 h with diazoxide (an opener of MitoK(ATP) channel); (3) 5-HD group: normal ASMCs were cultured under normoxia for 24 h with 5-hydroxydecanoate (5-HD) (an antagonist of MitoK(ATP) channel); (4) Asthma group: Asthmic ASMCs were cultured under normoxia for 24 h; (5) Asthma + diazoxide group: Asthmic ASMCs were cultured under normoxia with diazoxide for 24 h; (6) Asthma + 5-HD group: Asthmic ASMCs were cultured under normoxia with 5-HD for 24 h. The mitochondrial membrane potential (ΔΨm) was detected using Rhodamine 123 (R-123). The level of reactive oxygen species (ROS) was detected by DCF fluorescence. The expression of nuclear factor-kappa B (NF-κB) mRNA was examined by RT-PCR. The proliferation and apoptosis of rat ASMCs were examined respectively by MTT colorimetric assay and cell cycle analysis. The results were as follows. (1) After exposure to diazoxide for 24 h, the R-123 fluorescence intensity, the ROS level, NF-κB mRNA expression and the MTT absorbance value (A value) in normal ASMCs were significantly increased, and the apoptosis of rat ASMCs was significantly decreased compared to the control group (P0.05). However, there was no significant changes in those indices after the normal ASMCs had been exposed to 5-HD for 24 h. (2) In Asthma and Asthma + diazoxide groups, the R-123 fluorescence intensity, ROS level and the MTT A value were markedly increased, and the apoptosis was markedly decreased compared to control group (P0.05). These changes were more obvious in Asthma + diazoxide group than those in Asthma group (P0.05). 5-HD partly weakened the effect of asthma on the R-123 fluorescence intensity, ROS level and the MTT A value and the apoptosis of rat ASMCs (P0.05). R-123 fluorescence intensity and NF-κB mRNA expression were positively correlated with ROS level. NF-κB mRNA expression was positively correlated with the MTT A value and negatively correlated with the apoptosis of rat ASMCs. All the results suggest that the opening of MitoK(ATP) channel followed by a depolarization of ΔΨm contributes to the increase in ROS level and NF-κB mRNA expression in rat ASMCs and to the unbalance between cell proliferation and apoptosis of ASMCs induced by asthma. This might be a mechanism of the development of airway remodeling in asthma.

The objectives of this paper were to observe the changes of reactive oxygen species (ROS) in rat pulmonary arterial smooth muscle cells (PASMCs) under hypoxic condition and to test if hypoxia-induced proliferation of PASMCs was mediated by ROS. PASMCs were divided into three groups: normal group, hypoxia group and hypoxia + Mn-TBAP (a ROS scavenger) group. The level of ROS was determined by a laser scanning confocal microscope. The expression of hypoxia-inducible factor 1alpha (HIF-1alpha) mRNA was detected by semi-quantitative reverse transcription PCR (RT-PCR). HIF-1alpha protein was detected using immunohistochemical staining, and the proliferation of PASMCs was examined by MTT colorimetric assay. The results were as follows: (1) The level of ROS in hypoxia group was significantly increased as compared with that in the normal group (P0.05). The level of ROS in hypoxia + Mn-TBAP group was significantly decreased as compared with that in hypoxia group (P0.05), but was increased as compared with that in the normal group (P0.05). (2) The expressions of HIF-1alpha mRNA and protein in hypoxia group and hypoxia + Mn-TBAP group were increased as compared with those in the normal group (P0.05), and these changes were more significant in hypoxia group than those in hypoxia + Mn-TBAP group. (3) The proliferation of PASMCs in hypoxia group was more obvious than that in the normal group and hypoxia + Mn-TBAP group (P0.05), and the proliferation of PASMCs in hypoxia + Mn-TBAP group was increased more significantly than that in the normal group (P0.05). The results indicate that ROS is significantly increased in rat PASMCs under hypoxia, and that ROS affects the expression of HIF-1alpha and the proliferation of PASMCs under hypoxia. Therefore, ROS may play an important role in the pathogenesis of pulmonary hypertension and hypoxic signal transductions.

The objective of this paper was to investigate the effect of mitochondrial ATP-sensitive K(+) (MitoK(ATP)) channels on the expression of hypoxia inducible factor-1alpha (HIF-1alpha) and cell proliferation in pulmonary arterial smooth muscle cells (PASMCs) of rats. Cultured PASMCs were divided into six groups as follows: (1) normoxia group: cultured under normoxia for 24 h; (2) normoxia + diazoxide group: cultured under normoxia with diazoxide, an opener of MitoK(ATP) channel, for 24 h; (3) normoxia + 5-HD group: cultured under normoxia with 5-hydroxydecanoate (5-HD), an antagonist of MitoK(ATP) channel, for 24 h; (4) hypoxia group: cultured under hypoxia (37 degrees C, 5% O(2), 5% CO(2), 90% N(2)) for 24 h; (5) hypoxia + diazoxide group: cultured under hypoxia (37 degrees C, 5% O(2), 5% CO(2), 90% N(2)) with diazoxide for 24 h; (6) hypoxia + 5-HD group: cultured under hypoxia (37 degrees C, 5% O(2), 5% CO(2), 90% N(2)) with 5-HD for 24 h. The relative changes in mitochondrial potential were tested with Rhodamine 123 (R-123) fluorescence technique. Immunohistochemical method was used to trace the expression of HIF-1alpha. The proliferation of PASMCs was examined by MTT colorimetric assay. The results were as follows: The intensity of R-123 fluorescence in normoxia + diazoxide group was significantly increased as compared with that in normoxia group (P0.05), and the intensity of R-123 fluorescence in hypoxia + diazoxide group was also significantly increased as compared with that in hypoxia group (P0.05). 24-hour hypoxia or 24-hour hypoxia + diazoxide markedly increased the intensity of R-123 fluorescence in PASMCs as compared with normoxia (P0.05), and the change was more prominant in hypoxia + diazoxide group than that in hypoxia group (P0.05). There was no significant difference in the intensity of R-123 fluorescence between normoxia group and normoxia + 5-HD group (P0.05). However, 5-HD weakened the effect of 24-hour hypoxia on the intensity of R-123 fluorescence. The intensity of R-123 fluorescence in hypoxia + 5-HD group was significantly decreased as compared with that in hypoxia group (P0.05). After exposure to hypoxia or hypoxia + diazoxide for 24 h, the expression of HIF-1alpha and the proliferation of PASMCs were significantly increased as compared with that in normoxia or normoxia + diazoxide group (P0.05), and the change was more significant in hypoxia + diazoxide group than that in hypoxia group (P0.05). There was no significant difference in the expression of HIF-1alpha and the proliferation of PASMCs between normoxia group and normoxia + 5-HD group (P0.05). However, the expression of HIF-1alpha and the proliferation of PASMCs in hypoxia + 5-HD group were significantly decreased as compared with that in hypoxia group (P0.05). All these results suggest that the opening of MitoK(ATP) channels followed by a depolarization of mitochondrial membrane might contribute to the increase of the expression of HIF-1alpha and the proliferation of PASMCs. This might be a mechanism of the development of hypoxic pulmonary hypertension.

To investigate the contribution of the opening of mitochondrial ATP-sensitive K+ channel (MitoK(ATP)) and mitochondrial membrane potential (delta psi m) to changes of reactive oxygen species (ROS) and to the imbalance of proliferation/apoptosis of human pulmonary arterial smooth muscle cells (HPASMC) induced by hypoxia.HPASMC were divided into the following groups: (1) control group (A group): cultured under normoxia; (2) 5-HD group (B group): cultured in normoxia with 5-hydroxydecanoate (5-HD), an antagonist of MitoK(ATP), for 24 h; (3) diazoxide group (C group): cultured in normoxia with diazoxide, an opener of MitoK(ATP), for 24 h; (4) chronic hypoxia group (D group): cultured under hypoxia for 24 h; (5) chronic hypoxia + diazoxide group (E group): cultured in hypoxia with diazoxide for 24 h; (6) chronic hypoxia + 5-HD group (F group): cultured in hypoxia with 5-HD for 24 h. The relative changes in mitochondrial potential were tested with rhodamine fluorescence (R-123) technique. The level of ROS in HPASMC was tested with chemiluminescence method. The proliferation of HPASMC was examined by the expression of PCNA, c-fos and c-jun proteins, and by MTT colorimetric assay.The mitochondrial membrane potentials (expressed by intensity of R-123) of C group (105 +/- 4), D group (95 +/- 13) and E group (126 +/- 8) were significantly depolarized as compared with A group (75 +/- 7, q = 5.474, 3.659, 9.213, all P0.05). The levels of ROS of C group (3045 +/- 126), D group (3116 +/- 34) and E group (3236 +/- 31) were significant increased than that of A group (2772 +/- 49) (q = 6.882, 7.448, 16.289, all P0.05). The cell viability of C group (0.305 +/- 0.022), D group (0.328 +/- 0.078) and E group (0.440 +/- 0.023) were significant increased than that of A group (0.237 +/- 0.013) in HPASMC (q = 2.993, 4.017, 8.919, all P0.05). The mitochondrial membrane potential, the level of ROS and the cell viability in HPASMC of E group were significantly different as compared with D group (q = 5.554, 8.841, 4.902, all P0.05). The mitochondrial membrane potential (71 +/- 4), the level of ROS (2863 +/- 132) and the cell viability (0.264 +/- 0.045) of F group were significantly decreased than those of D group (95 +/- 13, 3 116 +/- 34, 0.328 +/- 0.078, q = 4.367, 5.907, 2.832, all P0.05).The results suggested that the opening of MitoK(ATP) followed by a depolarization of delta psi m might contribute to the increasing of the level of ROS in HPASMC, and play an important role in the proliferation of HPASMC. This might be a mechanism for the development of hypoxic pulmonary hypertension.

The objective of this paper was to investigate the contribution of mitochondrial ATP-sensitive K+ channel (mitoK(ATP)) and mitochondrial membrane potential (Deltapsim) to the distribution of cytochrome C in human pulmonary arterial smooth muscle cells (HPASMCs) and to the proliferation of HPASMCs induced by hypoxia. HPASMCs were divided into 6 groups, as following: (1) control group: cultured under normoxia; (2) diazoxide group: cultured in normoxia with diazoxide, an opener of mitoK(ATP); (3) 5-HD group: cultured in normoxia with 5-hydroxydecanoate (5-HD), an antagonist of mitoK(ATP); (4) 24-hour hypoxia group: cultured in hypoxia for 24 h; (5) 24-hour hypoxia + diazoxide group: cultured in hypoxia with diazoxide for 24 h; (6) 24-hour hypoxia + 5-HD group: cultured in hypoxia with 5-HD for 24 h. The relative changes in mitochondrial potential were tested with rhodamine fluorescence (R-123) technique. Western blot was used to detect the expression of cytochrome C protein in cell plasma and mitochondria,respectively. The expression of cell caspase-9 protein was determined with Western blot. The proliferation of HPASMCs was examined by cell cycle analysis and MTT colorimetric assay. The results were as following: after exposure to diazoxide for 24 h, the intensity of R-123 fluorescence in normoxic HPASMCs was significantly increased compared with that in the control group (P0.05), but there was no significant change of the intensity of R-123 fluorescence after the HPASMCs had been exposed to 5-HD for 24 h; 24-hour hypoxia or 24-hour hypoxia + diazoxide could markedly increase the intensity of R-123 fluorescence in HPASMCs compared with normoxia (P0.05), and the change was more significant in 24-hour hypoxia + diazoxide group than that in 24-hour hypoxia group (P0.05); 5-HD could weaken the effect of 24-hour hypoxia on the intensity of R-123 fluorescence. After exposure to diazoxide for 24 h, the ratio of the expression of cytosolic cytochrome C protein to that of mitochondrial cytochrome C protein was significantly decreased compared with that in the control group (P0.05), and the expression of caspase-9 protein was significantly decreased compared with that in the control group (P0.05). The percentage of S phase and A value of MTT were significantly increased compared with those in the control group (P0.05). But there were no significant changes in these tests after HPASMCs had been exposed to 5-HD for 24 h (P0.05). After exposure to hypoxia or hypoxia + diazoxide for 24 h, the ratio of the expression of cytosolic cytochrome C protein to that of mitochondrial cytochrome C protein and the expression of caspase-9 protein were significantly decreased compared with those in the control group (P0.05). The percentage of S phase and A value of MTT were significantly increased compared with those in the control group (P0.05). These changes were more significant in 24-hour hypoxia + diazoxide group than those in 24-hour hypoxia group (P0.05). 5-HD could weaken the effect of hypoxia on the changes of the distribution of cytochrome C, the expression of caspase-9 in HPASMCs and the proliferation of HPASMCs induced by hypoxia (P0.05). All these results suggest that the opening of mitoK(ATP) followed by a depolarization of Deltapsim induced by hypoxia might contribute to the inhibition of the release of cytochrome C from mitochondria to plasma in HPASMCs. This might be a mechanism of the development of hypoxic pulmonary hypertension. The signal transduction pathway of mitochondria might play an important role in the relationship between Deltapsim and apoptosis of HPASMCs.