异甘草酸镁治疗大鼠非酒精性脂肪性肝炎及其作用机制

摘要

Objective To explore the therapeutic efficacy and the mechanism of magnesium isoglycyrrhirzinate on rats with non acoholic steatohepatitis. Methods A total of 50 male Srague Dawley rats were randomly assigned into 5 groups. The rats in the control(N) group were fed with common food, the model Ⅰ(M1) group and model Ⅱ(M2) groups were fed with high-fat diets, the treatment group(T1) rats were treated with magnesium isoglycyrrhizinate and dietary therapy group(T2) rats were fed with high-fat diets until 12 weeks. The T2 group rats were then treated with common food and the rats in T1 group were treated with magnesium isoglycyrrhizinate(120 mg·kg·d-1). The rats in N and M1 group were killed at the end of thel2th week and while the ones in M2, T1 and T2 group at the end of the 16th week. Liver function tests(AST and ALT), lipid metabolism(TC, TG, HDL and LDL-C) and lipid peroxidation(MDA, SOD and GSH) parameters were measured and histopathological changes of liver were observed. Results The rats in M1 group developed NASH after 12 weeks.The rats in the N group had aggravated hepatic fatty degeneration and inflammnation, increased TC, TG, LDL-C and MDA, and decreased HDL, SOD and GSH conpared to the control group(P＜0.05). The degree of NASH aggravated, and the AST and ALT levels were increased after week 16 in the M2 group(P＜0.05). The parameters and the degree of severity of hepatic fat degeneration in T1 group were all improved compared to the M1 and M2 groups(P＜0.05). But there was no significant change in the T1 group(P＞0.05). Conclusion Magnesium isoglycyrrhizinate therapy can improve lipid metabolism disorder, anti-lipid peroxidation, and anti-inflarmmation in patients with non acoholic steatohepatitis.%目的 探讨异甘草酸镁对非酒精性脂肪性肝炎(NASH)的治疗作用及其作用机制.方法 雄性SD大鼠50只随机分为5组:正常组(N组)普通饲料喂养;模型Ⅰ组(M1组)和模型Ⅱ组(M2组)高脂饲料喂养;异甘草酸镁治疗组(T1组)和饮食治疗组(T2组)在喂饲高脂饲料12周后改为普通饲料喂养,其中T2组同时给予异甘草酸镁120mg·kg<'-1>·d<'-1>尾静脉注射.12周末处死N和M1组大鼠;16周末处死M2、T1和T2组大鼠.观察各组大鼠肝脏组织病理学改变,并测定各组大鼠肝功能(血清AST、ALT)、脂代谢(血清TC、TG、HDL、LDL-C)及脂质过氧化(肝匀浆MDA、SOD、GSH)指标.结果 12周末M1组大鼠出现NASH,肝脏的脂肪变性程度和炎症活动度均显著增高,TC、TG、LDL-C、MDA明显升高,HDL、SOD和GSH明显降低(JP<0.05);16周末,M2组大鼠NASH程度进一步加重,并出现AST和ALT的明显升高(P<0.05).和M1、M2组相比,T1组脂肪变性和炎症活动程度明显减轻,肝功能、脂代谢和脂质过氧化各项指标均改善(P<0.05);而T2组差异无统计学意义(P>0.05).结论 异甘草酸镁可能通过抗脂质过氧化、调节血脂代谢、抑制炎症反应等作用减轻NASH大鼠肝脂肪变性和炎症,对NASH有治疗作用.