H_2S通过MAPK信号通路影响缺血再灌注损伤大鼠回肠上皮细胞凋亡  

Role of hydrogen sulfide in ileal epithelial cell apoptosis by MAPK signaling pathway in rats with intestinal ischemia-reperfusion injury

作　　者：卢根林[1] 吴爱兵[2] 王宏宾[3] 

机构地区：[1]义乌市中心医院普通外一科,浙江义乌322000 [2]广东医学院附属医院肿瘤中心,广东湛江523808 [3]青海大学附属医院肝胆胰外科,青海西宁810001

出　　处：《中国病理生理杂志》2016年第4期691-695,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金青年科学基金资助项目(No.81201672);义乌市人才引进立项项目(No.2012-R-04)

摘　　要：目的:建立大鼠肠缺血再灌注(I/R)损伤模型,研究H2S对I/R损伤大鼠回肠上皮细胞凋亡、MAPK信号通路表达的影响。方法:30只雄性Wistar大鼠随机分为假手术(sham)组、I/R组、I/R+Na HS组。建立大鼠肠I/R损伤模型。再灌注前10 min时经大鼠尾静脉注入100μmol/kg Na HS,随后按1 mg·kg^(-1)·h^(-1)输注直到再灌注2 h。RT-PCR检测回肠组织ERK、JNK和p38MAPK的mRNA表达,Western blot检测回肠组织p-ERK、p-JNK、p-p38MAPK、p-NF-κB P65的蛋白水平。TUNEL染色检测回肠上皮细胞凋亡。敏感硫电极法测定血、回肠组织匀浆中的H2S浓度。结果:I/R组的H2S浓度、ERK、mRNA、p-ERK均低于sham组和I/R+Na HS组,JNK mRNA、p38MAPK mRNA、p-JNK、p-p38MAPK、p-NF-κB P65和凋亡指数高于sham组和I/R+Na HS组。结论:H_2S通过下调ERK的mRNA表达及磷酸化,上调JNK、p38MAPK mRNA的表达,促进JNK、p38MAPK、NF-κB磷酸化,从而减轻I/R损伤大鼠的回肠上皮细胞凋亡。AIM： To investigate the effect of hydrogen sulfide（ H_2S） on the expression of MAPKs and ileal epithelial cell apoptosis in the rats with intestinal ischemia-reperfusion（ I / R） injury. METHODS： Healthy female Wistar rats were randomly divided into sham operation group,I / R group,I / R ＋ sodium hydrosulfide（ Na HS） group. The animal model of intestinal ischemia reperfusion was established. Apoptosis index（ AI） of ileal epithelial cell was measured by TUNEL assay. H_2 S was detected by sensitive sulfide electrode. The mRNA expression of ERK,JNK and p38 MAPK was detected by RT-PCR. The protein levels of phosphorylation（ p）-ERK,p-JNK,p-NF-κB P65 and p38 MAPK were determined by Western blot. RESULTS： H_2 S,ERK mRNA and p-ERK in I / R group were significantly higher than those in I /R ＋ Na HS group and sham group while JNK mRNA,p38 MAPK mRNA,p-JNK,p-p38 MAPK,p-NF-κB P65 and AI were predominantly higher than those in I / R ＋ Na HS group and sham group（ P 0. 01）. CONCLUSION： H2 S attenuates ileal epithelial cell apoptosis in the rats with intestinal I / R injury by down-regulating ERK mRNA p-ERk and up-regulating JNK mRNA,p38 MAPK mRNA and phosphorylation of JNK,p38 MAPK and NF-κB P65.

关 键 词：缺血再灌注损伤 硫化氢 MAPK信号通路 细胞凋亡 

分 类 号：R363[医药卫生—病理学] R656.7[医药卫生—基础医学]