雌激素预处理增强肝缺血再灌注损伤大鼠雌激素受体表达

摘要

OBJECTIVE To investigate the effect of estrogen pretreatment on estrogen receptor (ER) expression in hepatic ischemia/reperfusion injury (I/R) in rats.METHODS A hepatic I/R model was constructed using Pringle's method.Estradiol 4 mg·kg-1 was injected intraperitoneally before hepatic ischemia.The level of serum alanine aminotransferase (ALT) and tumor necrosis factor-α(TNF-α) levels, nuclear factor (NF)-κB and estrogen receptor α (ERα) expression, and hepatic tissue were measured pre-ischemia( R0), post-reperfusion 1 h( R1 ), 3 h( R3 ), 6 h(R6)and 24 h (R24).RESULTS The levels of ALT and TNF-α and the expression of NF-κB and ERαin I/R group and estrogen + I/R group were increased compared to sham group.The level of ALT in R6 were increased 11.7 times and 8.1 times in I/R and estrogen + I/R groups compared to sham group.The level of TNF-α at R6 was increased 5.2 and 3.2 times compared to sham group, but the increase in I/R group was more significant than in estrogen + I/R group.The expression of NF-κB increased 8.6 and 4.8 times of I/R and estrogen + I/R group compared to sham group at R6, the expression of ERα was increased 4.2 and 7.4 times, but the degree increased of estrogen + I/R group was more marked than in ERα of I/R group.The liver damage in I/R group was more severe than that of estrogen + I/R group.CONCLUSION Estrogen pretreatment can decrease the levels of ALT and TNF-α and the expression of NF-κB, and alleviate hepatic I/R injury by upregulation of ERα expression.%目的 探讨雌激素预处理对肝缺血再灌注(I/R)损伤大鼠雌激素受体(ERα)表达的影响.方法 采用Pringle法阻断大鼠第一肝门制作95%肝I/R模型.肝缺血前1 h大鼠ip给予雌二醇4 mg·kg-1(雌二醇+I/R组).分别取肝缺血前(0)、再灌注1,3,6和24 h共5个时间点的血液标本,检测血清谷丙转氨酶(ALT)水平;ELISA法测定血清肿瘤坏死因子-α(TNF-α)水平;HE染色观察肝组织形态学变化,免疫组化方法检测肝核因子κB(NF-κB)和ERα的表达.结果 与假手术组相比,I/R模型组和雌二醇+I/R组血清ALT和TNF-α水平、肝组织NF-κB和ERα表达明显升高(P<0.01);与假手术组相比,再灌注6 h,I/R和雌二醇+I/R组血清ALT水平分别升高了11.7倍和8.1倍(P<0.01),TNF-α水平分别升高5.2倍和3.2倍(P<0.01),但雌二醇+I/R组升高幅度明显低于I/R组(P<0.05);与假手术组相比,再灌注6 h I/R组和雌二醇+I/R组肝组织NF-κB表达分别升高了8.6倍和4.8倍,但雌二醇+I/R组升高幅度明显低于I/R组(P<0.01); ERα表达分别升高了4.2倍和7.4倍,雌二醇+I/R组升高幅度明显高于I/R组(P<0.01);雌二醇+I/R组肝组织损伤明显轻于I/R组.结论 雌激素预处理可减轻I/R导致的肝组织损伤程度,此作用与增强ERα表达有关.