硫化氢在休克肠淋巴液致肝损伤中的作用与机制  

Role of hydrogen sulfide in alleviation of liver injury by mesenteric lymph drainage in hemorrhagic shock rats

作　　者：韩波[1,2] 张立民[1] 陈立锋[1] 赵自刚[1] 李曙光[1] 牛春雨[1] 

机构地区：[1]河北北方学院微循环研究所,河北张家口075029 [2]内蒙古自治区乌兰察布市中心医院,内蒙古乌兰察布012000

出　　处：《中国病理生理杂志》2013年第7期1307-1312,共6页Chinese Journal of Pathophysiology

基　　金：河北省科技支撑计划(No.11276103D-84);河北省高校百名创新人才支持计划(No.CPRC047);河北省人才培养工程资助计划

摘　　要：目的:应用硫化氢(H2S)合成酶胱硫醚γ-裂解酶(CSE)抑制剂DL-炔丙基甘氨酸(PPG)和H2S供体硫氢化钠(NaHS)作用于行肠淋巴液引流的大鼠,探讨H2S在肠淋巴液引流减轻休克大鼠肝损伤中的作用。方法:休克组、休克+引流组、休克+引流+PPG组(45 mg/kg,放血前0.5 h,ip)和休克+引流+NaHS(28μmol/kg,放血前0.5 h,ip)组大鼠复制失血性休克模型,低血压1 h后行液体复苏,休克+引流组、休克+引流+PPG组和休克+引流+NaHS组在输液结束后,行肠淋巴液引流至液体复苏结束后3 h。观察肝组织形态,检测血浆肝功能生化指标以及肝组织H2S、CSE、Toll样受体4(TLR4)、白细胞介素(IL)-10、IL-12和肿瘤坏死因子α(TNF-α)水平。结果:休克组大鼠血浆天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、总胆汁酸(TBA)以及肝组织H2S、CSE、TLR4、IL-10、IL-12、TNF-α含量均显著高于假手术组;肠淋巴液引流显著降低了休克组大鼠血浆AST、ALT、TBA以及肝组织H2S、CSE、IL-10、IL-12、TNF-α含量;PPG使休克+引流组大鼠血浆AST、ALT、TBA以及肝组织H2S、TLR4、IL-10、IL-12、TNF-α含量进一步降低;NaHS则提高了休克+引流组大鼠血浆AST、ALT与肝组织H2S、TLR4、IL-10、IL-12、TNF-α的含量。组织形态学观察表明,休克组和休克+引流+NaHS组大鼠出现了肝细胞损伤,假手术组、休克+引流组、休克+引流+PPG组大鼠肝细胞形态基本正常。结论:肠淋巴液引流减轻失血性休克大鼠肝损伤的作用机制与抑制H2S生成、减轻H2S介导的炎症反应有关。AIM： To investigate the role of hydrogen sulfide（H2S） in alleviation of liver injury by mesenteric lymph drainage in hemorrhagic shock rats.METHODS： A hemorrhagic shock model was established in male Wistar rats.DL-propargylglycine（PPG）,an inhibitor of cystathionine γ-lyase（CSE） which is a synthase of H2S,or sodium hydrosulfide（NaHS）,a donor of H2S,was administered to the hemorrhagic shock rats with mesenteric lymph drainage.The rats were randomly divided into sham,shock,shock ＋ drainage,shock ＋ drainage ＋ PPG（45 mg / kg,ip,0.5 h before hemorrhage） and shock ＋ drainage ＋ NaHS（28 μmol / kg,ip,0.5 h before hemorrhage） groups.Fluid resuscitation was performed 1 h after hypotension,and then mesenteric lymph was drained in the rats of shock ＋ drainage,shock ＋ drainage ＋ PPG and shock ＋ drainage ＋ NaHS groups for 3 h.The hepatic histomorphology was observed.The biochemical indexes of hepatic function in plasma,and H2S,CSE,Toll-like receptor 4（TLR4）,interleukin（IL）-10,IL-12 and tumor necrosis factor α（TNF-α） in hepatic homogenate were also examined.RESULTS： The levels of aspartate aminotransferase（AST）,alanine aminotransferase（ALT） and total bile acid（TBA） in plasma,and H2S,CSE,TLR4,IL-10,IL-12 and TNF-α in hepatic homogenate in shock group were significantly higher than those in sham group.Mesenteric lymph drainage obviously reduced these indexes in shock rats,except for TLR4.PPG further decreased these indexes except for CSE,while NaHS increased these indexes except for TBA and CSE.Morphological observation showed that liver injury appeared in the rats from shock and shock ＋ drainage ＋ NaHS groups,and there was nearly normal hepatic structure in the rats from sham,shock ＋ drainage and shock ＋ drainage ＋ PPG groups.CONCLUSION： The mechanism of mesenteric lymph drainage alleviating liver injury in hemorrhagic shock rats is related to reducing the production of H 2 S and alleviating the H 2 S-mediated inflammation.

关 键 词：休克 出血性 肠淋巴液 引流术 肝损伤 硫化氢 炎症 

分 类 号：R363[医药卫生—病理学]