阻断糖皮质激素受体对肝总动脉结扎大鼠肝功能的影响

目的 观察肝缺血损伤与糖皮质激素受体(GR)通路之间的关系,为从提高GR的途径减轻肝脏缺血后损伤提供理论依据.方法 208只SD大鼠随机分为正常对照组(n=8)、单纯结扎组(n=40)、阻断50％ GR组(n=40)、阻断80％GR组(n=40)、阻断50％GR伴结扎组(n=40)、阻断80％GR伴结扎组(n=40).采用肝总动脉结扎的方法建立大鼠肝缺血模型,动态观察肝总动脉结扎后GR的变化及GR阻断对模型大鼠血清肝功能指标[丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)]和肝脏组织结构的影响.结果 肝总动脉结扎后,GR阻断组与单纯结扎组相比,ALT、AST、ALP较单纯结扎组峰值升高,且随着GR阻断程度加深呈现酶峰提前,恢复时间延长的趋势；肝脏组织炎性浸润、缺血坏死程度也较单纯结扎组明显加重.免疫组织化学提示GR阻断后,肝总动脉结扎2h时肝细胞内GR较单纯结扎组明显减少,6h达到最低,其中80％阻断组较50％阻断组减少更为明显.结论 GR的减少对肝缺血后损伤发生的过程具有重要影响.

Effect of blockage of the glucocorticoid receptor on the liver function of rats after ligation of the common hepatic artery

Objective To provide a theoretical basis for alleviating liver injury due to ischemia by improving the glucocorticoid receptor(GR) through observation of the relationship between liver injury due to ischemia and the pathway of the GR.Method A total of 208 SD rats were divided randomly into normal control(NC) group(n=8),simple ligation group(model group,n=40),blockage of 50% GR group(n=40),blockage of 80% GR group(n=40),blockage of 50% GR accompanied by ligation group(50% GR+M group,n=40),and blockage of 80% GR accompanied by ligation group(80% GR+M group,n=40).Ligation of common hepatic artery was adopted to reproduce a model of liver ischemia in rat,and to dynamically observe the changes in GR after the ligation of the common hepatic artery.The effects of blocking the GR on the liver functional parameters of rat serum [alanine aminotransferase(ALT),aspartate aminotransferase(AST),and alkaline phosphatase(ALP)],and the structure of liver tissue were observed.Results After the ligation of the common hepatic artery,peak values of serum ALT,AST,and ALP in the GR blockage group were higher than those of the simple ligation group.Furthermore,with increase in the degree of GR blockage,there was a tendency that the peak values of the enzyme value appeared earlier and the time of recovery to normal was delayed.In addition,the degree of inflammatory infiltration and ischemia necrosis of liver tissues were more severe than that in the simple ligation group.Immunohistochemistry revealed that after blockage of GR,GR in liver tissues was notably lower 2h after ligation than that in the simple ligation group,reaching its trough value at 6h.This phenomenon was more obvious in the 80% GR blockage group than that in the 50% GR blockage group.Conclusion The decrease of GR has an important effect on the course of liver ischemic injury.