【摘要】 目的观察大黄素对刀豆蛋白(Con A)诱导小鼠急性肝损伤的干预作用,并探讨其机制。方法雄性Balb/C小鼠随机分为对照组、模型组、大黄素组。大黄素组按25 mg/kg给予大黄素灌胃,2 h后经尾静脉注射20 mg/kg的Con A诱导急性肝损伤模型。模型组以大黄素溶剂代替大黄素预处理,2 h后以同法制作急性肝损伤模型。对照组不做特殊处理。Con A注射10 h后摘眼球取血,检测各组小鼠血清ALT、AST;无菌取肝脏,进行肝组织病理检查评估肝组织损伤程度,采用实时荧光定量PCR法检测肝组织中的糖皮质激素诱导的肿瘤坏死因子受体(GITR)mRNA及糖皮质激素诱导的肿瘤坏死因子受体配体(GITRL)mRNA。结果模型组血清ALT、AST水平显著高于对照组,大黄素组血清ALT、AST水平低于模型组(P均<0.01)。相较于对照组,模型组小鼠肝组织出现明显坏死灶,而大黄素组小鼠肝组织坏死明显减轻。模型组GITR、GITRL mRNA相对表达量高于对照组,大黄素组GITR、GITRL mRNA相对表达量低于模型组(P均<0.05)。模型组GITR、GITRL蛋白相对表达量高于对照组,大黄素组GITR、GITRL蛋白相对表达量低于模型组(P均<0.05)。结论大黄素可能通过抑制GITR/GITRL通路而减轻Con A诱导的小鼠急性肝损伤。更多还原

【Abstract】 Objective To study the intervention effect of emodin on Con A-induced acute liver injury in mice and the underlying mechanism. Methods The male Balb/C mice were randomly divided into the control group, model group, and emodin group. Emodin(25 mg/kg) was administered orally, and Con A(20 mg/kg) was given through intravenous injection at 2 h after emodin administration in the emodin group. In place of emodin, CMC-Na was used in the model group, and mice in the control group were not treated.After 10 h of Con A injection, the blood was collected from the retro-orbital sinus in mice and the serum levels of ALT and AST were measured. Hepatic sections were aseptically obtained for histopathological examination to assess the degree of liver damage. The real-time fluorescent quantitative PCR and Western blotting were employed to evaluate the expression of glucocorticoid-induced tumor necrosis factor receptor(GITR) mRNA and its ligand GITRL mRNA.Results The serum ALT and AST levels in the model group were significantly higher than those in the control group, while those in the emodin group were lower than those in the model group(all P<0.01). Compared with the control group, there were more significant necrosis foci in the liver tissues of the model group, while the liver necrosis was significantly reduced in the emodin group. The relative expression levels of GITR and GITRL mRNA in the model group were higher than those in the control group, while the relative expression levels of GITR and GITRL mRNA in the emodin group were lower than those in the model group(all P<0.05). The relative expression levels of GITR and GITRL protein in the model group were higher than those in the control group, while the relative expression levels of GITR and GITRL protein in the emodin group were lower than those in the model group(all P<0.05). Conclusion Emodin alleviates Con A-induced liver damage by inhibiting GITR/GITRL pathway.更多还原