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The present study aimed to determine the inhibitory effects of angiotensin II (AngII) on angiopoietin-like protein 2 (Angptl2) in rat primary cardiomyocytes, and to investigate the potential association between angiotensin II type 1 receptor (AT1R) and these effects. Cardiomyocytes were isolated from 3-day-old Wistar rats, and were cultured and identified. Subsequently, the expression levels of Angptl2 were detected following incubation with various concentrations of AngII for various durations using western blotting, reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay and immunofluorescence. Finally, under the most appropriate conditions (100 nmol/l AngII, 24 h), the cardiomyocytes were divided into six groups: Normal, AngII, AngII + losartan, normal + losartan, AngII + PD123319 and normal + PD123319 groups, in order to investigate the possible function of AT1R in Angptl2 suppression. Losartan and PD123319 are antagonists of AT1R and angiotensin II type 2 receptor, respectively. The statistical significance of the results was analyzed using Student's t-test or one-way analysis of variance. The results demonstrated that Angptl2 expression was evidently suppressed (P<0.05) following incubation with 100 nmol/l AngII for 24 h. Conversely, the expression levels of Angptl2 were significantly increased in the AngII + losartan group compared with the AngII group (P<0.01). However, no significant difference was detected between the AngII + PD123319, normal + losartan or normal + PD123319 groups and the normal group. The present in vitro study indicated that AngII was able to suppress Angptl2 expression, whereas losartan was able to significantly reverse this decrease by inhibiting AT1R. [ABSTRACT FROM AUTHOR]

Background: Our previous studies indicated that heat stress can cause significant damage to the intestinal epithelium and induce differential expression of many genes in rat small intestine. The transcription factors AP-1 and NF-κB, which act as important mediators by binding to specific DNA sequences within gene promoters, regulate the transcription of genes associated with immune regulation, stress response and cell fate. Methods: To determine whether AP-1 and NF-κB are involved in hyperthermia-induced injury in rat small intestine and IEC-6 cells, we investigated their activity, and the expression of related proteins, by electrophoretic mobility shift assays and western blotting, respectively. Results: Heat stress resulted in severe damage to the epithelium of the small intestine. The cell morphology and viability were obviously altered when IEC-6 cell was exposed to hyperthermia. AP-1 was activated in the small intestine of heat-stressed rats, as was phosphorylation of the JNK signaling pathway. In IEC-6 cell line, AP-1 activation in groups exposed to 42 °C for 1 h, 2 h and 4 h was significantly increased. In contrast, NF-κB was not activated in both in vivo and in vitro models. Conclusion: These results reveal that AP-1 is likely to play an important role in regulating gene transcription in rat small intestine and IEC-6 cells during exposure to heat stress. [ABSTRACT FROM AUTHOR]

Testosterone can affect cardiovascular disease, but its effects on mitochondrial dynamics in the post-infarct myocardium remain unclear. To observe the effects of testosterone replacement, a rat model of castration-myocardial infarction (MI) was established by ligating the left anterior descending coronary artery 2 weeks after castration with or without testosterone treatment. Expression of mitochondrial fission and fusion proteins was detected by western blot and immunofluorescence 14 days after MI. Cardiac function, myocardial inflammatory infiltration and fibrosis, cardiomyocyte apoptosis, mitochondrial microstructure, and ATP levels were also assessed. Compared with MI rats, castrated rats showed aggravated mitochondrial and myocardial insults, including mitochondrial swelling and disordered arrangement; loss of cristae, reduced mitochondrial length; decreased ATP levels; cardiomyocyte apoptosis; and impaired cardiac function. Results of western blotting analyses indicated that castration downregulated peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1A) and mitofusin 2, but upregulated dynamin-related protein 1. The results were also supported by results obtained using immunofluorescence. However, these detrimental effects were reversed by testosterone supplementation, which also elevated the upstream AMP-activated protein kinase (AMPK) activation of PGC1A. Thus, testosterone can protect mitochondria in the post-infarct myocardium, partly via the AMPK-PGC1A pathway, thereby decreasing mitochondrial dysfunction and cardiomyocyte apoptosis. The effects of testosterone were confirmed by the results of ELISA analyses. [ABSTRACT FROM AUTHOR]

[Objective] The aim was to study the heat stress mechanism of differentially expressed genes in rat jejunal mucosal. [Method] Variable cluster analysis and cluster analysis of samples on the differentially expressed heat stress genes in rat jejunal mucosal were carried out with SAS software, and statistics of distribution of the differentially expressed genes on chromosomes were conducted. [Result] The differentially expressed genes were divided into seven categories, of which, the upregulated genes included three categories(i.e.: Category A: Hspa1 a, Hspa1 b,Hspb1, Hsph1, Dnaja4, Ahsa2 and P4ha1; Category B: Cyp1a2, Zbtb16, Gucy2 g,Fgb, Cyp4a3 and Etv2; and Category C: Cyp1a2, Chac1 and Cyp4b1) and the down-regulated genes included four categories(i.e.: Category D: Tlr2, Noxo1,LOC286989 and Aspg; Category E: RGD1560395, Alb and BQ194726; Category F:Ccl4, Gzmk, AI228153, Anxa10, S100a9 and Ascl5; and Category G: Reg1 a and Slc13a1). The classification, function and reasons of differential expression for each gene category were analyzed. [Conclusion] Most of the three categories of up-regulated genes were related to the heat shock proteins; and most of the four categories of down-regulated genes were related to the immunity, providing reference for discussion of the heat stress mechanism. [ABSTRACT FROM AUTHOR]

Background: Asthma is a chronic inflammatory disease of the mucosa and is associated with excess TH2 cytokines, eotaxin, prostaglandin D2 (PGD2) and eosinophilia in the lungs. Previous studies have emphasized that the N-terminal peptide of annexin 1 (peptide Ac2-26) can inhibit mast cell degranulation, antigen-induced eotaxin release as well as the accumulation of both neutrophils and eosinophils in a model of rat pleurisy. The purpose of this study was to demonstrate anti-asthmatic effects of Ac2-26 in an asthma model and to explore possible mechanisms involved. Methods: The effect of Ac2-26 on TH2 cytokine release, eotaxin production, PGD2 levels and the development of pulmonary eosinophilic inflammation was compared with glucocorticoids in an asthmatic rat model. The study was conducted on rats sensitized and challenged with ovalbumin and plethysmography measured airway responsiveness. Bronchoalveolar lavage (BAL) histopathology and the levels of cytokines, chemokines as well as PGD2 were examined. Results: Our results showed that Ac2-26 suppressed the accumulation of eosinophils in airways, reduced IL-4, IL-5, IL-13, PGD2 and eotaxin levels in the BAL fluid, and lowered the expression of CRTH2. Exogenous PGD2 significantly attenuated the biological effects of Ac2-26. Conclusion: These results indicated that Ac2-26 exerted broad inhibitory effects on airway inflammation and hyperresponsiveness in a rat model of asthma. Exogenous PGD2 reversed the inhibitory effects of AC2-26 on eosinophil recruitment. Ac2-26 exhibited anti-asthmatic, immunomodulatory activity that was substantially mediated by decreasing PGD2 production and its CRTH2 receptor expression in vivo. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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Background: Repeated electroacupuncture (EA) stimulation is known to stimulate the activity of the hypothalamus-pituitary-adrenal axis, and to enhance the circulation level of estrogen in the ovariectomized rats. To explore the source of the increased circulation estrogen, the extragonadal aromatization was detected. Methods: Female rats were divided into five groups: 1) intact (INT), 2) intact with EA in specific points (INT+EA), 3) ovariectomized (OVX), 4) ovariectomized with EA in specific points (OVX+EA) and 5) ovariectomized with EA in non-specific points (OVX+C). Radiometric assay, Western blot and RT-PCR were adopted to determine the extragonadal aromatization in subcutaneous abdominal (SA) adipose and liver tissues of rats. The blood concentrations of estrogen, testosterone and corticosterone were measured by radioimmunoassay. Results: The aromatase activities of the SA adipose and liver tissues in the OVX+EA rats increased significantly (p < 0.01) compared with those in the INT, INT+EA and OVX rats. The 58-kDa aromatase protein and aromatase mRNA expressions normalized to β-actin in the OVX+EA rats' SA adipose tissues showed higher levels than those from corresponding tissues in the INT and INT+EA rats (p < 0.05). And the ratios of aromatase mRNA and protein to β-actin in the OVX+EA rats' liver tissues increased significantly compared with those in the OVX rats (p < 0.05). Furthermore, blood estrogen and corticosterone concentrations showed significant increase in the OVX+EA rats compared with the concentrations in the OVX and OVX+C rats (p < 0.05), but no statistical disparity occurred on the blood testosterone concentrations between the OVX+EA rats and the OVX ones. Conclusion: Both the subcutaneous abdominal adipose and the liver tissues contributed to the effects of electroacupuncture on the extragonadal aromatization to promote the blood concentrations of estrogen in the ovariectomized rats. [ABSTRACT FROM AUTHOR]

Abstract: Through whole-cell patch recordings in brainstem slices, the effects of histamine on neuronal activity of the lateral vestibular nucleus (LVN) were investigated. Bath application of histamine elicited a concentration-dependent excitation of both spontaneous firing (n =19) and silent (n =7) LVN neurons. Moreover, histamine induced a stable inward current in the LVN neurons (n =5) and the histamine-induced depolarization of membrane potential persisted in the presence of tetrodotoxin (n =4), indicating a direct post-synaptic effect of the histamine on the LVN neurons. Selective histamine H2 receptor antagonist ranitidine effectively blocked the histamine-evoked excitatory responses on the LVN neurons (n =4), but selective histamine H1 receptor antagonist triprolidine did not (n =4). In addition, selective histamine H2 receptor agonist dimaprit (n =3) rather than 2-pyridylethylamine (n =4), a selective histamine H1 receptor agonist, mimicked the excitatory action of histamine on LVN neurons. The results demonstrate that histamine excites the LVN neurons via post-synaptic histamine H2 receptors and suggest that the central histaminergic projection arising from the hypothalamus may modulate LVN neurons activity and actively influence the vestibular reflexes and functions. [Copyright &y& Elsevier]

Purpose: To study the anti-arthritic effect of total anthraquinone from Polygonum cuspidatum (TAPC) on type II collagen-induced arthritis (CIA) in rats, and to investigate the underlying mechanism(s). Methods: CIA rats were prepared and treated orally with TAPC at doses of 50, 100 and 200 mg/kg/day, for 24 days. Paw volume and arthritis score were measured prior to TAPC treatment, and subsequently at 3-day intervals on days 3, 6, 9, 12, 15, 18, 21 and 24. Serum levels of TNF-α, IL-6 and IL-17 were determined by enzyme-linked immunosorbent assay (ELISA), while synovial tissue TNF-α, IL-6 and IL-17mRNA expressions were assayed by real time-polymerase chain reaction (RT-PCR). Thymus and spleen indices were also determined. Results: TAPC (50, 100 and 200 mg/kg) significantly alleviated paw swelling (p < 0.05), arthritis scores (p < 0.05) and thymus and spleen indices (p < 0.05) of CIA rats, when compared with the control rats. In addition, TAPC significantly decreased serum levels of the pro-inflammatory cytokines TNF-α, IL-6 and IL-17 (p < 0.01); and down-regulated their mRNA expressions in synovial tissues (p < 0.01). Conclusion: These results suggest that TAPC exerts good anti-arthritic activity in rats, most probably via suppression of inflammatory responses. [ABSTRACT FROM AUTHOR]

Summary: The absence of orexin results in narcolepsy-cataplexy. While the function of the central orexinergic system in sleep regulation has been well studied, the role of orexin in motor control is largely unknown. Here, we show that orexin-A acts via OX1 and OX2 receptors to directly depolarize neurons in the rat lateral vestibular nucleus (LVN), a subcortical motor center, and enhance their sensitivity. A dual ionic mechanism involving both Na+-Ca2+ exchangers and inward rectifier K+ channels underlies these effects. Furthermore, orexin-A regulates central vestibular-mediated posture, motor balance and negative geotaxis. Orexin is critical when an animal is facing a major motor challenge as opposed to during rest and general movements. Therefore, orexin participates not only in sleep and emotion (nonsomatic) but also in motor (somatic) regulation, suggesting that the central orexinergic system plays an important role in somatic-nonsomatic integration. These findings may account for why the absence of orexin results in narcolepsy-cataplexy. [Copyright &y& Elsevier]

Background: Asthma is a chronic inflammatory disease of the mucosa and is associated with excess TH2 cytokines, eotaxin, prostaglandin D2 (PGD2) and eosinophilia in the lungs. Previous studies have emphasized that the N-terminal peptide of annexin 1 (peptide Ac2-26) can inhibit mast cell degranulation, antigen-induced eotaxin release as well as the accumulation of both neutrophils and eosinophils in a model of rat pleurisy. The purpose of this study was to demonstrate anti-asthmatic effects of Ac2-26 in an asthma model and to explore possible mechanisms involved. Methods: The effect of Ac2-26 on TH2 cytokine release, eotaxin production, PGD2 levels and the development of pulmonary eosinophilic inflammation was compared with glucocorticoids in an asthmatic rat model. The study was conducted on rats sensitized and challenged with ovalbumin and plethysmography measured airway responsiveness. Bronchoalveolar lavage (BAL) histopathology and the levels of cytokines, chemokines as well as PGD2 were examined. Results: Our results showed that Ac2-26 suppressed the accumulation of eosinophils in airways, reduced IL-4, IL-5, IL-13, PGD2 and eotaxin levels in the BAL fluid, and lowered the expression of CRTH2. Exogenous PGD2 significantly attenuated the biological effects of Ac2-26. Conclusion: These results indicated that Ac2-26 exerted broad inhibitory effects on airway inflammation and hyperresponsiveness in a rat model of asthma. Exogenous PGD2 reversed the inhibitory effects of AC2-26 on eosinophil recruitment. Ac2-26 exhibited anti-asthmatic, immunomodulatory activity that was substantially mediated by decreasing PGD2 production and its CRTH2 receptor expression in vivo. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]