硫化氢对低氧性肺动脉高压大鼠细胞因子的调节作用

The regulatory effect of hydrogen sulfide on the cytokines of hypoxic pulmonary hypertensive rats

目的探讨硫化氢对低氧性肺动脉高压大鼠细胞因子的调节作用。方法将Wistar大鼠22只随机分为3组。对照组(8只),低氧组(7只),低氧+硫氢化钠(NaHS)组(7只),测定3组大鼠肺动脉平均压(mPAP),观测肺血管结构变化,并用免疫组织化学方法研究α-平滑肌肌动蛋白(-αSM-actin)、弹力蛋白、转化生长因子β(TGF-β)和结缔组织生长因子(CTGF)在肺动脉平滑肌细胞的表达含量。结果低氧组的mPAP明显高于对照组和低氧+NaHS组;低氧组肌型动脉、部分肌型动脉百分比明显高于对照组和低氧+NaHS组,非肌型动脉百分比明显低于对照组和低氧+NaHS组;低氧组肺中、小型肺动脉平滑肌细胞-αSM-actin、弹力蛋白和TGF-β表达含量分别明显高于对照组和低氧+NaHS组;对照组、低氧+NaHS组以及低氧组肺中、小型肺动脉平滑肌细胞CTGF表达含量依次增高,但3组之间无显著差异。结论硫化氢可能通过调节低氧性肺动脉高压大鼠肺小血管肌性动脉TGF-β的表达,进而抑制细胞外基质成分之一的弹力蛋白合成,参与低氧性肺动脉高压的形成。

Objective To investigate the regulatory effect of hydrogen sulfide（HS） on the cytokines of hypoxic pulmonary hypertensive（HPH） rats.Methods Twenty-two rats were randomly divided into three groups：control group, hypoxic group and hypoxia ＋ NaHS group. Pulmonary artery mean pressure （mPAP） of rats of three groups was measured. The percentage of muscularized arteries of small pulmonary arteries was measured. The expression of α-smooth-muscle actin（α-SM-actin）, elastin, TGF-β and CTGF in pulmonary artery smooth muscle cells was observed with immunohistochemistry. Results mPAP was significantly higher in rats of hypoxic group than those of control group and hypoxia ＋ NaHS group. The percentage of muscularized arteries and partly muscularized arteries of small pulmonary arteries was increased in rats of hypoxic group as compared with that in control group and hypoxia ＋ NariS group, while the percentage of unmuscularized arteries of small pulmonary arteries was decreased in rats of hypoxic group compared with that in control group and hypoxia ＋ NaHS group. The expression of α-SM-actin, elastin and TGF-β of median and small pulmonary artery smooth muscle cells in hypoxic group significantly increased compared with those in control group and hypoxia ＋ NaHS group. The expression of CTGF of median and small pulmonary artery smooth muscle cells in control group, hypoxic group and hypoxia ＋ Naris group gradually increased in turn, but it was not significantly different between the three groups. Conclusion The results showed that hydrogen sulfide might play a modulatory role in the development of HPH through regulating the expression of TGF-β in muscularized small pulmonary arteries and further inhibiting the expression of elastin of extracellular matrix in hypoxic rats.