外源性硫化氢对家兔内毒素休克诱发肺动脉高压的干预作用  

Effects of exogenous hydrogen sulfide on pulmonary hypertension in rabbits with endotoxic shock

作　　者：郭赞[1] 刘宜先[1] 齐杰[2] 羡晓辉[2] 黄新莉[2] GUO Zan;LIU Yi-xian;QI Jie;XIAN Xiao-hui;HUANG Xin-li(Department of Physiology,Hebei Medical University,Shijiazhuang 050017,China;Department of Pathophysiology,Hebei Medical University,Shijiazhuang 050017,China)

机构地区：[1]河北医科大学生理教研室,石家庄050017 [2]河北医科大学病理生理教研室,石家庄050017

出　　处：《中国应用生理学杂志》2022年第3期264-269,共6页Chinese Journal of Applied Physiology

基　　金：国家自然科学基金资助项目(30800440);河北省自然科学基金资助项目(C2008001040,H2016206191,C2020206050);河北省教育厅重点项目(ZD2017050)资助。

摘　　要：目的:探讨外源性硫化氢(H_(2)S)对家兔内毒素休克(ES)诱发肺动脉血管反应性的影响。方法:本实验采用家兔经颈静脉注射脂多糖(LPS,8 mg/0.8 ml/kg)复制家兔ES模型,并提前15 min腹腔注射H_(2)S供体硫氢化钠(NaHS,28μmol/kg)进行干预。随机将新西兰大耳白家兔分为4组(n=8):溶剂对照组、LPS组、LPS+NaHS组和NaHS组。监测平均动脉压(MAP)和平均肺动脉压(MPAP)的变化;应用血管环张力测定技术,检测各组家兔离体肺动脉张力变化;应用光镜和扫描电镜分别观察肺动脉管壁结构及肺动脉内皮细胞超微结构变化。结果:①注射LPS后家兔出现MAP降低、MPAP升高,成功复制家兔ES模型;与LPS组相比,LPS+NaHS组家兔MPAP在各个时间点均显著降低(P均﹤0.05);②与正常对照组相比,LPS组家兔肺动脉对苯肾上腺素(PE)的收缩反应增强,对乙酰胆碱(ACh)的舒张反应降低(P均﹤0.01);与LPS组相比,LPS+NaHS组家兔肺动脉对PE的收缩反应降低,而对ACh的舒张反应增强(P均﹤0.05)。③光镜下可见正常对照组家兔血管内皮细胞结构连续,内皮下弹力纤维完整,平滑肌层排列整齐;LPS组家兔部分肺动脉内皮细胞脱落,内皮下弹力纤维断裂,平滑肌层结构紊乱;与LPS组相比,LPS+NaHS组家兔肺动脉壁各层损伤减轻;NaHS组肺动脉壁各层形态结构接近正常对照组。扫描电镜检查发现LPS组家兔肺动脉部分内皮细胞缺失;LPS+NaHS组肺动脉内皮细胞形态接近对照组,仅可见细胞间隙稍增宽,未见细胞脱落。结论:外源性H_(2)S可保护肺动脉内皮细胞,调节ES时肺动脉反应性的改变,从而降低ES家兔PAH。Objective:To investigate the effects of exogenous hydrogen sulfide(H_(2)S)on pulmonary vascular reactivity induced by endotoxic shock(ES)in rabbits.Methods:In this experiment,the model of endotoxic shock(ES)was induced by injection of lipopolysaccharides(LPS)to New Zealand big eared white rabbit through jugular vein(8 mg/0.8 ml/kg),the intervention was performed by H_(2)S donor(sodium hydrosulfide,NaHS)which was injected intraperitoneally(28μmol/kg)15 min in advance.New Zealand rabbits were randomly divided into 4 groups(n=8):control group,LPS group,LPS+NaHS group and NaHS group.The changes of mean arterial pressure(MAP)and mean pulmonary arterial pressure(MPAP)were detected.The tension of pulmonary artery ring(PARs)was detected by in vitr o vascular ring technique.The ultrastructure of pulmonary artery wall and pulmonary artery endothelial cells were observed by light microscope and scanning electron microscope.Results:①MAP was decreased while MPAP was increased in rabbits after LPS injection,and ES animal model was established successfully.Compared with LPS group,mPAP of rabbit in LPS+NaHS group was decreased significantly(all P<0.05).②Compared with normal control group,pulmonary artery of rabbits in LPS group had an increased contractile response to phenylephrine(PE)and a decreased relaxation response to acetylcholine(ACh)(both P<0.01);Compared with LPS group,pulmonary artery of rabbits in LPS+NaHS group had a decreased contractile response to PE and an increased relaxation response to ACh(both P<0.05).③Under light microscope,the structure of vascular endothelial cells was continuous in the normal control group,the elastic fibers were intact in the subcutaneous layer,and the smooth muscle layer was arranged neatly.LPS can shed some of the pulmonary artery endothelial cells,break the subcutaneous elastic fibers,and disorder the smooth muscle layer structure.Compared with LPS group,the injury of pulmonary artery wall in LPS+NaHS group was ameliorated.The morphology of pulmonary artery wall was normal in N

关 键 词：硫化氢 脂多糖 休克 肺动脉 家兔 

分 类 号：R363.2[医药卫生—病理学]