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内源性硫化氢在脂多糖引起的肺动脉高压中的作用

黄新莉, 周晓红, 韦鹏, 张晓静, 孟祥艳, 羡晓辉

河北医科大学病理生理学教研室.河北,石家庄 050017

摘要

为观察硫化氢(hydrogen sulfide, H_(2)S)在脂多糖引起的肺动脉高压中的作用，应用离体血管环张力测定方法测定肺动脉反应性，采用生物化学方法测定肺动脉组织中H_(2)S产出率和胱硫醚--#gamma#--裂解酶(cystathionine #gamma#--lyase, CSE)活性，定量PCR方法测定肺动脉组织中CSE表达水平。结果如下：(1)与对照组相比，LPS可显著升高肺动脉平均压(mean pulmonary artery pressure, mPAP) [(1.82±0.29) kPa vs (1.43±0.26) kPa, {sl P}<0.01]，降低肺动脉组织中H_(2)S产出率[(42.92±8.73) vs (26.33±7.84) pmol/g wet tissue per minute, {sl P}<0.01]和肺动脉内皮依赖性舒张反应[(75.72±7.22)% vs (86.40±4.40)%]；(2) NaSH可部分逆转上述变化，而PPG加剧上述变化；(3) CSE活性和CSE mRNA表达的变化与H_(2)S产出率的变化相同。结果提示， LPS对内皮依赖性舒张反应的抑制导致肺动脉高压的发生，此作用可能与H_(2)S有关。

关键词： 脂多糖; 硫化氢; 肺动脉高压

Role of endogenous hydrogen sulfide in pulmonary hypertension induced by lipopolysaccharide

Huang Xinli, Zhou Xiaohong, WEI Peng, Zhang Xiaojing, Meng Xiangyan, Xian Xiaohui

Department of Pathophysiology, Hebei Medical University.Shijiazhuang 050017,Hebei

Abstract

The purpose of the present study was to explore the role of endogenous hydrogen sulfide (H_(2)S) in pulmonary arterialhypertension induced by endotoxin. Adult male Sprague-Dawley (SD) rats were randomly divided into four groups: Control group(0.5 mL/kg body weight of normal saline, i.v.), lipopolysaccharide (LPS)-treated group (5 mg/kg body weight of LPS, i.v.), LPS+NaHS(5 mg/kg body weight of LPS, i.v., and 28 #mu#mol/kg body weight of NariS, i.p.) and LPS + PPG group (5 mg/kg body weight of LPS, i.v.,and 30 #mu#mol/kg body weight of PPG, i.p.). Rats were anesthetized with 20% urethane (1 g/kg body weight, i.p.). A polyethylene catheterwas inserted into the pulmonary artery through the fight external jugular vein to measure the mean pulmonary arterial pressure (mPAP)for 7 h, and then the pulmonary artery was isolated rapidly by the method described previously. Pulmonary arterial activity was detected.H_(2)S concentration and cystathionine #gamma#-lyase (CSE) activity in pulmonary artery tissues were determined by biochemical method. CSE mRNA expression was detected by competitive reverse transcriptase-polymerase chain reaction (RT-PCR). Compared with control,LPS significantly increased mPAP [(1.82±0.29) kPa vs (l.43±0.26)kPa, P<0.01], decreased H_(2)S production [(26.33±7.84) vs (42.92±8.73)pmol/g wet tissue per minute, P<0.01), and reduced endothelium-dependent relaxation response [(75.72±7.22)% vs (86.40±4.40)%,P<0.01) induced by ACh (1×10~(-6) mol/L). These effects were partly reversed by co-administration of NariS and enhanced by co-administration of PPG. Both CSE activity and CSE mRNA expression were consistent with H_(2)S production. It is suggested that theinhibitory effect of LPS on endothelium-dependent relaxation results in pulmonary hypertension, which might be mediated through H_(2)S.

Key words: Lipopolysaccharide;hydrogen sulfide;Pulmonary hypertension

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引用本文：

黄新莉, 周晓红, 韦鹏, 张晓静, 孟祥艳, 羡晓辉. 内源性硫化氢在脂多糖引起的肺动脉高压中的作用[J]. 生理学报 2008; 60 (2): 211-215.

Huang Xinli, Zhou Xiaohong, WEI Peng, Zhang Xiaojing, Meng Xiangyan, Xian Xiaohui. Role of endogenous hydrogen sulfide in pulmonary hypertension induced by lipopolysaccharide. Acta Physiol Sin 2008; 60 (2): 211-215 (in Chinese with English abstract).