硫化氢在脓毒症大鼠心肌损伤中的作用

摘要

目的 研究硫化氢(H2S)在脓毒症大鼠心肌损伤中的作用.方法 雄性SD大鼠60只,月龄3～4个月,体质量180 ～220 g,随机(随机数字法)分为4组:对照组(Ⅰ组)、脓毒症组(Ⅱ组)、脓毒症+ NaHS(H2S供体)预处理组(Ⅲ组)、脓毒症+PAG(H2S代谢酶CSE抑制剂)组(Ⅳ组),每组各15只.采用盲肠结扎穿孔法制作脓毒症大鼠模型,观察各组大鼠血流动力学改变,测定心肌组织中H2S的变化,采用RT-PCR方法观察CSE mRNA表达,采用髓过氧化物酶(MPO)测定试剂盒测定各组心肌组织MPO含量,用ELISA方法检测心肌组织TNF-α、IL-1β的表达,光学显微镜下观察心肌形态学改变.结果 与Ⅰ组相比,Ⅱ组血压下降,心肌组织中H2S、TNF-α、IL-1β、MPO含量出现不同程度增加(P＜0.01或P＜0.05),CSE mRNA表达水平提高(P＜0.05)；与Ⅱ组相比,Ⅲ组血压下降更为显著,心肌组织中H2S、TNF-α、IL-1β含量增加,MPO活性增强(P＜0.05),但CSE mRNA表达水平并无显著改变；与Ⅱ组相比,Ⅳ组血压水平接近,心肌组织中H2S、TNF-α、IL-1β 含量均降低,MPO活性减弱(P＜0.05),CSE mRNA表达水平下降(P＜0.05).四组心肌组织形态学损伤由轻到重依次为Ⅰ、Ⅳ、Ⅱ、Ⅲ.结论 脓毒症大鼠心肌组织CSE/H2S体系上调,给予H2S可以升高脓毒症大鼠心肌组织中MPO、TNF-α、IL-1β水平,加重心肌损伤,给予H2S抑制剂可以减轻心肌损伤.%Objective To investigate the effects of hydrogen sulfide on sepsis-induced cardiac dysfunction in rats.Methods Male SD rats were randomly ( random number) divided into 4 groups:control group ( Ⅰ group),sepsis group ( Ⅱ group),sepsis + NaHS group (Ⅲ group),sepsis + PAG group (Ⅳ group). Cecal ligation and puncture technique was used in Ⅱ, Ⅲ, Ⅳ group. Hemodynamic was observed,and H2S synthesis,CSE (cystathionine-r-lyase) mRNA,MPO activity and the level of TNF-α,IL-1β were determined.The morphological changes and infiltration of inflammatory cells in myocardium were also observed.Results Compared with Ⅰ group,H2S synthesis,the levels of TNF-α,IL-1 β,the activity of MPO increased ( P ＜ 0.05 or P ＜ 0.01 ),and the expression of CSE-mRNA increased,and blood pressure of rats decreased significantly in Ⅱ group.Compared with Ⅱ group,H2S synthesis,the levels of TNF-α,IL-1β and the activity of MPO increased (P ＜ 0.05),the expression of CSE mRNA did not change noticeably ( P ＞ 0.05),and blood pressure of rats decreased more significantly in Ⅲ group.Compared with Ⅱ group, H2S level decreased,the levels of TNF-α,IL-1β and the activity of MPO decreased significantly,the expression of CSE mRNA decreased and blood pressure of rats decreased in Ⅵ group (P ＜0.05).Histopathological changes of myocardium were aggravated in the following severity order: Ⅰ ＜ Ⅳ ＜＜ Ⅲ.Conclusions CSE/H2S system of the myocardium was upregulated in sepsis rats.Hydrogen sulfide could raise the levels of MPO,TNF-α,IL-1β,aggravating myocardial injury. Contrarily,the inhibitor of H2S could counteract it.