新型气体信号分子硫化氢对吸烟大鼠气道炎症和气道反应性的影响

Role of Endogenous Hydrogen Sulfide in Airway Inflammation and Airway Responsiveness in a Rat Model of Chronic Passive-Smoking

目的探讨气体信号分子硫化氢(H2S)对被动吸烟大鼠气道炎症和气道反应性的影响。方法36只SD雄性大鼠随机分为对照组和被动吸烟组,每组18只。被动吸烟组给予被动吸入香烟烟雾(CS)处理,对照组呼吸清洁空气。两组按照处理方式不同[腹腔注射生理盐水、硫氢化钠(NaHS)、炔丙基甘氨酸(PPG)]相应分别下分为Con组、NaHS组和PPG组,以及CS组、CS+NaHS组和CS+PPG组。4个月后取大鼠左肺进行病理学观察并予评分,测定各组大鼠气道反应性,采用敏感硫电极测定血浆及肺组织H2S水平,Westernblot测定肺组织胱硫醚γ裂解酶(CSE)蛋白表达。结果CS组肺组织CSE蛋白表达较Con组增加(P<0.05)。与Con组比较,NaHS组、CS组、CS+NaHS组血浆H2S含量显著增高,而PPG组明显降低(P均<0.05);与CS组比较,CS+NaHS组血浆中H2S含量显著增高,而CS+PPG组显著降低(P均<0.05)。各组大鼠肺组织匀浆中H2S含量差异无统计学意义。与Con组比较,CS组大鼠气道壁炎症病理评分明显升高,气道对乙酰胆碱(ACh)和氯化钾(KCl)的反应性增高;与CS组比较,CS+NaHS组气道壁炎症病理评分降低(P<0.05),气道反应性下降(P<0.05),而CS+PPG组气道壁炎症病理评分明显升高(P<0.05),气道反应性进一步升高(P<0.01)。结论新型气体信号分子H2S能够减轻吸烟导致的气道炎症和气道高反应性,为内源性保护因子之一。

Objective To investigate the role of endogenous Hydrogen Sulfide （H2S） in airway inflammation and responsiveness in a rat model of chronic passive-smoking. Methods Male SD rats were randomly divided into a control group （ breathing fresh air） and a passive smoking group [ cigarette smoking （CS） passively] ,with 18 rats in each group. Six rats in each group were randomly intraperitoneally injected with normal saline, sodium hydrosulfide （NariS） or propargylglycine （PPG, an irreversible inhibitor of cystathionine- γ-lyase）. The animals were divided into six subgroups, ie. Con group, NariS group, and PPG group, CS group, CS ＋ Naris group, and CS ＋ PPG group. After 4 months,lung histological change and airway tension were measured. The HE S levels of plasma and lung tissue were analyzed by the sensitive sulphur electrode assay. The expression of cystathionine-γ-lyase （ CSE ） was measured by western blot. Results Compared with the Con group, CSE protein expression in lung tissues was increased in CS group （P 〈 0. 05 ） ; the H2 S levels of plasma were significantly higher in CS group, Naris group and CS ＋ NariS group, and much lower in PPG group（ P 〈 0.05, respectively）. Compared with CS group, the H2S levels of plasma were significantly higher in CS ＋ NariS group, and much lower in CS ＋ PPG group （ P 〈 0. 05, respectively）. The H2S level of lung tissue in each group had no significant difference （P 〉 0. 05 ）. Compared with Con group, score of lung pathology was significant elevated, and the responsiveness of airway smooth muscles to ACh and KCl was significant augmented in CS group. Compared with CS group, the score of lung pathology was decreased, and the responsiveness of airway smooth muscles was decreased in CS ＋ NariS group（ P 〈 0. 05 ）, and vise versa in CS ＋ PPG group （ P 〈 0. 01 ）. Conclusion H2S can alleviate airway inflammation and hyperresponsiveness induced by CS, and administration of H2S might be of clinical benefit in airway inflammation and airway responsiveness.