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Summary: The relations between mRNA expression of basic fibroblast growth factor (bFGF) and the changes in collagen I and collagen III in pulmonary tissues from a single intratracheal instillation of papain-induced emphysema in rats were investigated. Wistar rats (n = 42) were randomly divided into normal group and emphysema model 1, 3, 5, 7, 15, 30-day groups (n=6 in each group). The rat model of emphysema was induced by a single intratracheal instillation of papain. The results of immunohistochemistry SABC and in situ hybridization with bFGF probe were quantitatively analyzed to examine the changes of collagen I and collagen III and bFGF mRNA expression in lung tissues and the percent of positive expression of bFGFmRNA in alveolar macrophages. The results were as follows: (1) In the emphysema model groups the optical densities of collagen I and collagen III began to increase after 3 days, reached the highest at the 7th day, and began to reduce at the 15th day; (2) No expression of bFGFmRNA in pulmonary tissues was detectable in the normal group. The positive expression of bFGFmRNA was detectable in lung tissues one day after the intratracheal instillation of papain. The average optical densities reached the peak (41. 895±7. 017) at the 7th day, significantly higher than in the normal group (0. 581±0. 139,P<0. 01). The positive expression of bFGFmR-NA in lung tissues began to reduce at the 15th day; (3) Positive expression of bFGFmRNA in alveolar macrophages of instillation papain rats was detectable 3 days after the intratracheal instillation of papain, and reached the highest at the 7th day with the percent of positive expression of bFGF mR-NA in alveolar macrophages being 70. 13±11. 21, higher than in the normal group (5. 12±0. 18,P <0. 01); (4) The expression of bFGF mRNA in the lung tissues and macrophages was postively related with the changes in collagen I and collagen III (P<0. 01 orP<0. 05) respectively. It was suggested that the up-regulation of bFGF mRNA expression during the development of emphysema can lead pulmonary interstitial fibrosis, which may take part in the injury and repair and the lung tissue reconstruction.

Summary: To explore the regulatory role of protein kinase C (PKC) in the expression of Th2 cytokines, interleukin-4 (IL-4) and interleukin-5 (IL-5) by T lymphocytes in asthma. T lymphocytes were isolated and purified from blood and bronchial alveolus lavage fluid (BALF) of each guinea pig of normal control group and asthmatic group and from peripheral blood of the asthmatic patients and normal controls, and were stimulated with PKC accelerant phorbol 12-myristate 13-acetate (PMA) and inhibitor Ro31-8220. The expression of IL-4 and IL-5 mRNA and protein was detected by using in situ hybridization staining and ELISA respectively. The expression of IL-4 and IL-5 mRNA and protein of asthmatic T lymphocytes stimulated with PMA was significantly higher than that of asthmatic T lymphocytes stimulated without PMA respectively (P<0. 01) and that of normal T lymphocytes stimulated with PMA respectively (P<0. 01). The expression of IL-4 and IL-5 mRNA and protein of asthmatic T lymphocytes stimulated with PMA and Ro31-8220 was significantly lower than that of asthmatic T lymphocytes stimulated only with PMA respectively (P<0. 01). It was concluded that PKC might participate in regulating the expression of IL-4 and IL-5 in asthmatic T lymphocytes, and the activation of PKC in T lymphocytes might play an important role in the pathogenesis of asthma.

Summary: In order to measure the plasma levels of interleukin-4 (IL-4). cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in patients with chronic obstructive pulmonary disease (COPD) and observe the effects of oral theophylline on them, we divided 28 COPD patients into COPD experimental group and COPD control group. Plasma levels of IL-4, cAMP and cGMP as well as parameters of pulmonary function tests were measured in these 2 groups before and after 2 weeks of treatment with oral theophylline (Protheo, 400 mg, qd) or placebo. Plasma levels of IL-4 and cGMP were significantly elevated in patients with COPD as compared with normal controls (P< 0. 05), while cAMP and cAMP/cGMP were significantly lower than those in controls (P < 0. 01). Plasma level of IL-4 was inversely correlated with forced expiratory volume at the first second (FEV1) and with maximum expiratory flow rate at 50 % of forced vital capacity (V50) (bothr= −0.46,P< 0.05) while it was directly correlated with the scores of the clinical manifestations (r=0.57,P< 0.05) in COPD patients. Two weeks after treatment with theophylline, IL-4 and cGMP in COPD experimental group were decreased significantly while cAMP and cAMP/ cGMP increased significantly (P< 0. 05). The change of IL-4 was inversely correlated with the changes of FEV1, and V50(r=−0.53 and -0.54, respectively,P< 0. 05). Two weeks after placebo treatment, the COPD control group did not show such changes. We are led to conclude that IL-4 might play a role in the pathogenesis of the airway inflammation and air flow limitation in COPD patients and the mechanisms of theophylline’s therapeutic efrects of attenuating air-flow limitation may partially depend on its anti-inflammatory effects on the airways which, in turn, is dependent on its inhibitory effects on some inflammatory mediators such as IL-4.

Summary: In order to study the effect ofErigeron Breviscapus (EB) on proliferation of pulmonary artery smooth muscle cells (PASMC) in hypoxic porcines, immunohistochemical and MTT methods were employed to measure the proliferation of PASMC. It was found that the proliferation of PASMC in porcines was obvious, and the expression of proliferating cell nuclear antigen (PCNA) was significantly high within 48 h after exposure to hypoxia. The EB could inhibit the proliferation and the expression of PCNA in PASMC under hypoxia, but it had no effect on the proliferation and expression of PCNA in PASMC under normal condition. The EB could inhibit the proliferation and the expression of PCNA in PASMC induced by phorbol 12-myristate 13-acetate (PMA), an agonist of PKC in normal and hypoxic conditions. It was concluded that the hypoxia could enhance the proliferation and expression of PCNA in PASMC. The EB can inhibit the proliferation and expression of PCNA in PASMC under hypoxia through PKC-signal way. The EB may be used in treating the pulmonary hypertension by inhibiting the proliferation of PASMC and the pulmonary vascular remodeling.

Summary: The change of measurements of impulse oscillometry (IOS) in obstructive sleep apnea syndrome (OSAS) patients and its mechanism were observed. The respiratory impedance was measured by using IOS technique and polysomnography (PSG) was monitored synchronously in 36 OSAS patients, 14 patients with chronic obstructive pulmonary disease (COPD) and 12 normal controls. Results showed that R20 in OSAS group was significantly higher than in COPD group and control group (P < 0. 01). R5-R20 in OSAS group was lower than that in COPD group, but significantly higher than that in control group (P< 0. 01). The levels of R20 and R5-R20 were positively correlated with severity degree of the disease. In addition, apnea-hyponea index (AHI) was positively correlated with R5 and R20 with the correlation index (r)being 0. 66 and 0. 86 respectively. The lowest SO2 was negatively correlated with R5 and R5-R20, with r being -0. 66 and -0. 79 respectively. The mean SO2 was negatively correlated with R5 and R5-R20 with r being -0. 81 and -0. 69 respectively. IOS technique could be used as a valuable tool for assessing the degree of upper airway obstruction in the patients with OSAS, and could help to explore its pathological mechanism.

Summary: The levels of lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-α) expression in culture of peripheral blood mononuclear cells (PBMC) and the plasma levels of IL-6 and TNF-α in the patients with obstructive sleep apnea syndrome (OSAS) were measured and the relationship between OSAS and IL-6 or TNF-α expression studied. Both IL-6 and TNF-α were detected by using ELISA in 22 patients with OSAS and 16 normal controls. The levels of LPS-induced IL-6 (787.82±151.97 pg/ml) and TNF-α (4165.45±1501.43 pg/ml) expression in the supernatant of the culture of PBMC and plasma level of IL-6 (50.67±4.70 pg/ml) and TNF-α (299.09±43.57 pg/ml) in the patients with OSAS were significantly higher than those in the normal controls (in the supernatant of the culture of PBMC: 562.69±197.54 pg/ml and 1596.25±403.08 pg/ml respectively; in the plasma; 12.69±2.75 pg/ml and 101.88±21.27 pg/ml respectively). There were significantly positive correlation between the levels of IL-6 and TNF-α and the percentage of time of apnea and hyponea, as well as the percentage of time spending at SaO2 below 90 % in the total sleep time. It was concluded that LPS-induced IL-6 and TNF-α levels as well as plasma IL-6 and TNF-α levels in the patients with OSAS were up-regulated, which may be associated with the pathogenesis of OSAS.

Summary: To investigate the effects of intrinsic nitric oxide (NO) on the expression of interleukin-4 (IL-4) mRNA and interferon-γ (IFN-γ) mRNA in the airway inflammation of asthma, the rat models of asthmatic inflammaiton were established by sensitizing and then challenging the animals with ovalbumin. The 24 animals were randomly divided into control group, sensitized group, sensitized and L-Arg-treated group as well as L-NAME-treated group equally. By using in situ hybridization combined with compute physiological quantitative imaging analysis techniques, the influence of intrinsic NO on the expression of IL-4 mRNA and IFN-γ mRNA in the airway inflammatory cells was observed. In situ hybridization study demonstrated that IL-4 mRNA expression was obviously increased as compared with that in the control group, mainly distributed in the inflammatory cells in the submucous of airways in the sensitized group. The increase of intensity of IL-4 mRNA expression was positively correlated with the numbers of eosinophil (Eos) and lymphocyte (both with P < 0.05) in the sensitized group. There was no statistically difference in IFN-γ expression between the control group and the sensitized group. Imaging analysis showed that L-NAME could inhibit the expression of IL-4 mRNA (P < 0.05) and increase the expression of IFN-γ mRNA (P < 0.05), while L-Arg could increase the expression of IL-4 mRNA in inflammatory cells (P < 0.05). It was indicated that a suitable levels of intrinsic NO can influence the expression of IL-4 mRNA of Th2 lymphocytes and the expression of IFN-γ mRNA of Thl lymphocytes and in turn, promote the development of asthmatic airway inflammation.

Summary: In order to investigate the regulating role of Astragapolysaccharide (APS) in the mice model of asthmatic airway inflammation, the airway eosinophil number, spleen T lymphocyte proliferation, level of IL-2 production and their relationships were studied in sensitized mice and sensitized mice treated with different concentrations of APS. The results showed that the number of eosinophils as well as lymphocytes in the airway of the sensitized animals were significantly increased, and a marked positive correlation between the inflammation cells and spleen T lymphocyte proliferation was found. Moreover, there was a positive correlation between inflammation cells and the level of IL-2 production. The APS of given dosage could significantly reduce the number of eosinophils in the airway of the sensitized animals. At the same time the level of IL-2 secreted by spleen T lymphocytes stimulated with ConA was also significantly decreased and there was a marked positive correlation between them. Our results suggested that APS of given dosage could prevent antigen-induced the number of eosinophils infiltrating into the airway of sensitized mice and inhibit the proliferation and activation of lymphocyte and IL- 2 production. Through its immuno-regulating effect, APS can be helpful in the treatment of asthma.

Summary: The regulating effects of protein kinase C (PKC) on the tone of guinea-pig trachea and human lobus bronchi were investigated by measuring the tone of isolated tracheal and bronchial strips. The effects of PKC on the tone of guinea-pig tracheal and human lobus bronchi were observed and compared. The results showed that: (1) PKC activator PMA induced concentration-dependent relaxation in guinea-pig isolated trachea strips. This relaxation was completely ablated by the pretreatment with 5 × 10t-6mol/L Ro31-8220 which is a PKC-specific inhibitor, but was not affected by the removal of epithelium (EP), or by the pretreatment with propranolol (β-receptor blocker) or atropin (M-receptor blocker); (2) PMA led to concentration-dependent contraction in human lobus bronchi. This contractile response was completely depressed by the pretreatment with 5 × 10t-6 mol/L Ro31-8220 and was partly inhibited by 1 × 10t-5 mol/L isoptin (Ca2+-antagonist). but was not significantly affected by propranolol or atropin. It is concluded that PKC is involved in the regulation of airway smooth muscle tone. The regulating effects may vary in different animals.