硫化氢对肺动脉高压内皮细胞调控作用的研究

Regulation of Hydrogen Sulfide on Endothelial Cells of Pulmonary Hypertension

目的探讨硫化氢(H2S)对肺动脉高压内皮细胞的调控机制。方法将30只雄性SD大鼠随机分为对照组(n=10)、实验组(n=10)及NaHS干预组(n=10),行左颈总动脉和左颈外静脉近端吻合建立肺动脉高压动物模型,经腹腔注射NaHS(NaHS是外源性H2S的供体)56μmol/kg·d进行干预11w。实验结束后检测大鼠血流动力学、右心室肥厚指数等指标;利用TUNEL方法检测内皮细胞的凋亡情况;ELISA方法检测内皮素(ET-1)的表达情况。结果实验组和干预组大鼠肺动脉收缩压明显高于对照组(P<0.05),NaHS干预组大鼠肺动脉压力低于实验组(P<0.05);实验组和干预组大鼠内皮细胞凋亡指数显著高于对照组(P<0.05);实验组和干预组血清中ET-1蛋白表达明显高于对照组(P<0.05),而干预组血清中ET-1蛋白表达显著低于实验组(P<0.05)。结论H2S对肺动脉高压的调节可能通过抑制内皮细胞凋亡和降低内皮素表达来实现。

Objective To explore the regulation of hydrogen sulfide on pulmonary hypertension endothelial cells. Methods The 30 male SD rats were randomly divided into 3 groups including control group （n= 10）, experimental group （n= 10）, Naris intervention group （n= 10）. The high pulmonary blood flow model of pulmonary hypertension was established by performing left common carotid artery and left external vein proximal anastomosis in both the experimental group and intervention group. All animals were given intraperitoneal injection of NariS, which is a donor of exogenous H2 S in the intervention group. After 11 weeks, All animals were measured hemodynamics, right ventricular hypertrophy index, detected apoptosis of endothelial cells （Tunel） and expression of endothelin-1 （ELISA）. Results After 11 weeks, pulmonary artery pressure in experimental group and intervention group were significantly higher than that of control group （P〈0.05）. Index of endothelial cells apoptosis and expression of plasma endothelin-1 in experimental group and intervention group were significantly higher than that of control group （P〈0. 05） ,whereas index of endothelial cell apoptosis and expression of plasma endothelin-1 in intervention group were significantly lower than that of experimental group （P〈0. 05）. Conclusion Regulation of hydrogen sulfide on pulmonary hypertension is achieved, possibly through inhibition of endothelial cells apoptosis and decreasing expression of endothelin.