内源性硫化氢对吸烟大鼠小气道纤维化的保护作用

目的探讨内源性硫化氢（Hzs）对于吸烟诱导的COPD大鼠模型中小气道纤维化的影响。方法32只健康雄性SD大鼠随机分为正常组、吸烟组、吸烟＋Hzs组和吸烟＋炔丙基甘氨酸（PPG）组，采用被动烟雾吸入法，共吸烟4个月，从第3个月起，每日吸烟前给予大鼠腹腔注射生理盐水、硫氢化钠（NaHS）（14μmol／kg）或PPG（37．5mg／kg），取肺组织切片进行HE染色和天狼星红染色，观察肺组织病理形态改变，对小气道胶原沉积采用半定量分析，并进行小气道病理评分。Westernblot检测肺组织胱硫醚-γ-裂解酶（CGL）、I型胶原蛋白表达水平。结果与正常组比较，吸烟组小气道病理评分明显升高（P〈0．01），NaHS干预后较吸烟组评分降低（P〈0．05）。偏振光显微镜下观察天狼星红染色切片，吸烟组和吸烟＋PPG组较正常组小气道周围胶原沉积显著增多（P〈0．01），吸烟＋H2S组较吸烟组明显减少（P〈0．05）。与正常组相比，吸烟组大鼠肺组织I型胶原蛋白含量明显增多（P〈0．05），NariS干预后I型胶原蛋白含量较单纯吸烟组明显降低（P〈0．05）。结论内源性H2S参与吸烟诱导的COPD大鼠小气道纤维化的病理生理过程，外源性给予H2S对小气道纤维化具有保护作用。

Hydrogen sulfide protects against smoke-induced small airway fibrosis in rats

Objective To investigate the effect of hydrogen sulfide （H2S） in small airway fibrosis of rats with chronic obstructive pulmonary disease （COPD）. Methods Thirty-two male Sprague-Dawley rats were randomly divided into four groups ： control group, tobacco smoke group, smoke＋ H2 S group, and smoke＋ PPG group. Drug intervention started at the third month of a total four-month smoke exposure. Rats were intraperitoneally injected with normal saline, sodium hydrosulfide （NariS, 14 μmol/kg）, or PPG （37.5 mg/kg） before smoke every day. After four months, the histological change of lungs and the collagen deposition in airway were measured by HE staining and picrosiriu-red staining. The pathological score of small airway was calculated. The expressions of cystathionine y-lyase and collagen I were measured by Western blot. Results Compared with control group, the pathological score of small airway was significantly elevated in smoke group （ P 〈 0.01）, but decreased after Naris intervention （ P 〈 0.05）. Picrosiriu-red staining was detected under a polarided microscope. Compared with control group, the collagen deposition around the airway wall was increased in smoke group and smoke--PPG group （ P 〈 0.01）. And the collagen deposition in smoke＋ H2 S group was less than that in smoke group （ P 〈0.05）. Compared with control group,the expression of collagen I was significant elevated in smoke group （ P 〈 0.05） ,but decreased after NariS intervention （ P 〈0.05）. Conclusions Endogenous H2 S plays a crucial role in the small airway fibrosis in smoke-induced COPD rats. Exogenously applied H2 S could attenuate the process of airway fibrosis.