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

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。

Estrogen pretreatment upregulats estrogen receptor expression in rats with hepatic ischemia/reperfusion injury

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 ERα in 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 ZEstrogen 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.