玄参中6-O-甲基梓醇对果糖诱导的非酒精性脂肪性肝病的作用与机制初探  

The effect of 6-O-methyl-catalpol from Scrophulariae Radix on fructose-induced NAFLD and its mechanism

作　　者：李静[1] 尚平平[1] 田雪 何姣 乔博灵 孙文基[1] 房敏峰 LI Jing;SHANG Ping-ping;TIAN Xue;HE Jiao;QIAO Bo-ling;SUN Wen-ji;FANG Min-feng(Biomedicine Key Laboratory of Shaanxi Province,College of Life Science,Northwest University,Xian710069,China)

机构地区：[1]西北大学生命科学学院,陕西省生物医药重点实验室,西安710016

出　　处：《中国新药杂志》2023年第9期941-946,共6页Chinese Journal of New Drugs

基　　金：陕西省自然科学基金资助项目(2021JM-318)。

摘　　要：目的:探讨6-O-甲基梓醇对果糖诱导小鼠非酒精性脂肪性肝病(NAFLD)的治疗作用及其机制。方法:昆明种小鼠随机分为正常组(正常饮用水)和果糖组(30%果糖水),4周后果糖组随机分为模型组、水飞蓟宾组(35 mg·kg^(-1))、6-O-甲基梓醇低剂量组(30 mg·kg^(-1))和6-O-甲基梓醇高剂量组(60 mg·kg^(-1)),继续饮用果糖,给药组灌胃qd,持续4周后收集小鼠血清和肝组织标本。测定血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆固醇(TC)、三酰甘油(TG)、葡萄糖(GLU)、胰岛素(insulin)和瘦素(leptin)水平,HE染色观察肝组织病理变化,Western blot法检测肝组织乙酰辅酶A羧化酶(ACC)和脂肪酸合成酶(FAS)蛋白表达。结果:与模型组相比,6-O-甲基梓醇可显著降低小鼠血清ALT,AST,TC,TG和胰岛素、瘦素水平(P<0.01),显著降低小鼠胰岛素抵抗指数(HOMA-IR,P<0.01),减轻肝脏组织脂质沉积。6-O-甲基梓醇高剂量组能下调小鼠肝脏中ACC和FAS蛋白表达(P<0.01)。结论:6-O-甲基梓醇可通过减轻胰岛素抵抗和调节脂质代谢,对果糖诱导小鼠NAFLD有一定的保护作用。Objective:To observe the protective effect of 6-O-methyl-catalpol on fructose-induced NAFLD in mice and its mechanism.Methods:The mice were randomly divided into the control group and fructose-fed groups.After 4 weeks,the fructose-fed mice were further divided to 4 subgroups:model group,silybin group(35 mg·kg^(-1)),6-0-methyl-catalpol(30 mg·kg^(-1))group,and 6-0-methyl-catalpol(60 mg·kg^(-1))group.The drugs were administered by gavage qd for a period of 4 weeks.At the end of the treatment,the levels of ALT,AST,TC,TG,GLU,insulin and leptin were determined.The histopathological changes of liver were evaluated using HE staining.The fatty acid synthetase(FAS)and acetyl CoA carboxylase(ACC)protein expression in liver were measured using Western blot.Results:Compare with the model group,the elevated levels of AST,ALT,TC,TG,insulin,leptin and HOMA-IR significantly decreased in 6-O-methyl-catalpol groups(P<0.01).HE staining showed that the degree of hepatic steatosis was obviously ameliorated in 6-O-methyl-catalpol treatment groups.The protein expression levels of ACC and FAS were also significantly down-regulated in high 6-O-methyl-catalpol group(P<0.01).Conclusion:6-O-methyl-catalpol exerts protective effect against NAFLD,which may be related to the improvement of insulin sensitivity and lipid metabolism.

关 键 词：玄参 6-O-甲基梓醇 非酒精性脂肪性肝病 胰岛素抵抗 乙酰辅酶A羧化酶 脂肪酸合成酶 

分 类 号：R965.1[医药卫生—药理学] R975.5[医药卫生—药学]