甘草酸对非酒精性脂肪性肝炎大鼠治疗效果研究

Therapeutic Efficacy of Glycyrrhizic Acid on Rats with Non Alcoholic Steatohepatitis

目的研究甘草酸对非酒精性脂肪性肝炎(NASH)大鼠的治疗效果及其作用机制。方法雄性SD大鼠40只随机分为5组:正常组,模型组,低、中、高剂量甘草酸治疗组(60、120、180mg/kg),以高脂饮食喂养16周构建大鼠NASH模型,于造模第7周起进行不同剂量甘草酸治疗10周,HE染色观察肝组织病理学变化,并对总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、丙二醛(MDA)、超氧化物歧化酶(SOD)及还原型谷胱甘肽(GSH)进行检测。结果高脂饮食诱导的NASH大鼠模型中,肝组织可见肝细胞脂肪病变,血清中TC、TG、LDL-C、AST、ALT及MDA明显升高,HDL-C、SOD及GSH显著降低;而经过中、高剂量甘草酸治疗后发现,肝细胞脂肪病变程度降低,血清中TC、TG、LDL-C、AST、ALT及MDA明显降低,HDL-C、SOD及GSH明显升高,与模型组相比差异均具有统计学意义(P <0. 05)。结论甘草酸能够经过抑制氧化应激损伤、改变血脂水平来改善NASH大鼠肝功能及抑制肝脏病变程度,对NASH治疗具有潜在的临床意义。

Objective To study the therapeutic efficacy and the mechanism of glycyrrhizic acid on rats with non alcoholic steatohepatitis （NASH）. Methods A total of 40 male Srague Dawley rats were randomly divided into five groups, including control group, model group, low-, middle-, and high-dose of glycyrrhizic acid groups. Rats were given high-fat diet for 16 weeks to construct the NASH model. Since the seventh week after the model establishment, the rats were treated with 60, 120, 180mg/kg glycyrrhizic acid for ten weeks. The pathologic changes in hepatic tissues were investigated with HE staining. The levels and activity of total cholesterol （TC）, triglyceride （TG）, high density lipoprotein cholesterol （HDL-C）, low density lipoprotein cholesterol （LDL-C）, aspartate transferase （AST）, alanine aminotransferase （ALT）, malonaldehyde （MDA）, superoxide dismutase （SOD） and glutathione （GSH） were determined. Results The rats in the model group had aggravated hepatic fatty degeneration, increased TC, TG, LDL-C, AST, ALT and MDA, decreased HDL-C, SOD and GSH compared with control group （ P 〈0.05）. After treatment with middle- and high- dose of glycyrrhizic acid, the rats in the glycyrrhizic acid group had decreased hepatic fatty degeneration, decreased TC, TG, LDL-C, AST, ALT and MDA, increased HDL-C, SOD and GSH compared with model group （ P 〈0.05）. Conclusion Glycyrrhizic acid therapy can improve lipid metabolism disorder, and anti-lipid peroxidation in rats with non acoholic steatohepatitis, and it has a potential clinical significance for the treatment of NASH.