六味降脂汤对NAFLD大鼠肝脏脂肪酸代谢及LXRα-SREBP-1c-FAS信号通路的影响  

Effects of Liuwei Jiangzhi Decoction on hepatic fatty acid metabolism and LXRα-SREBP-1c-FAS signal pathway in NAFLD rats

作　　者：全德森 柯尊丽 张远哲 黎豫川 马晶鑫 刘林潇 田维毅 蔡琨 QUAN De-sen;KE Zun-li;ZHANG Yuan-zhe;LI Yu-chuan;MA Jing-xin;LIU Lin-xiao;TIAN Wei-yi;CAI Kun(College of Basic Medical Sciences,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China;Department of Pharmacy,The Second Hospital Affiliated to Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China)

机构地区：[1]贵州中医药大学基础医学院,贵州贵阳550025 [2]贵州中医药大学第二附属医院药学部,贵州贵阳550025

出　　处：《中成药》2023年第2期406-414,共9页Chinese Traditional Patent Medicine

基　　金：国家自然科学基金地区项目(82060797);贵阳市科技计划项目(筑科合同[2019]-9-4-19);贵州中医药大学博士基金项目([2019]22号,[2019]25号);贵州中医药大学第二附属医院院内科研项目(GZEYK[2020]7号)。

摘　　要：目的 探究六味降脂汤对非酒精性脂肪性肝病(NAFLD)大鼠的干预作用及其机制。方法 42只大鼠随机分为空白组、模型组、阿托伐他汀组(0.9 mg/kg)及六味降脂汤低、中、高剂量组(5.4、10.7、21.4 g/kg),给予高脂饲料合并高脂乳剂喂养6周建立NAFLD大鼠模型,造模成功后予相应药物干预2周后,检测血清ALT、AST、SOD活性及MDA、NEFA水平,检测肝组织TC、TG水平并计算肝脏指数,HE和油红O染色观察肝组织病理学改变,RT-qPCR和免疫组化(IHC)法检测肝组织LXRα、SREBP-1c、FAS mRNA和蛋白表达。结果 与空白组比较,模型组大鼠肝组织存在广泛较大的脂肪滴,脂肪变性明显,血清ALT、AST活性,MDA、NEFA水平及肝组织TC、TG水平,LXRα、SREBP-1c、FAS mRNA和蛋白表达均升高(P<0.01),肝组织SOD活性降低(P<0.01);与模型组比较,六味降脂汤各剂量组大鼠肝脏脂质沉积得到改善,脂肪变性程度减轻,血清ALT、AST活性,MDA、NEFA水平及肝组织TC、TG水平,LXRα、SREBP-1c、FAS mRNA和蛋白表达均降低(P<0.05,P<0.01),肝组织SOD活性升高(P<0.05,P<0.01)。结论 六味降脂汤具有调控肝脏脂肪酸代谢,减轻氧化应激反应,从而治疗NAFLD的作用,其潜在机制可能与抑制SREBP-1c-FAS信号通路有关。AIM To explore the effects and mechanism of Liuwei Jiangzhi Decoction on rats with nonalcoholic fatty liver disease(NAFLD).METHODS Forty-two rats were randomly divided into the blank group, the model group, atorvastatin group(0.9 mg/kg) and low, medium and high dose groups of Liuwei Jiangzhi Decoction(5.4, 10.7, 21.4 g/kg). The NAFLD rat model was established by feeding of high-fat diet and high-fat emulsion for 6 weeks. After the successful model establishment and the corresponding 2-week drug intervention, the rats had detection of their serum levels of ALT, AST, SOD activity and MDA, NEFA, and their hepatic TC and TG levels for the calculation of liver index level;observation of their hepatic pathological changes by HE and oil red O staining;determination of their hepatic mRNA and protein expressions of LXRα, SREBP-1c and FAS by RT-qPCR and immunohistochemistry(IHC).RESULTS Compared with the blank group, the model group displayed obvious steatosis and extensive and large fat droplets in the liver tissue;increased serum ALT and AST activities and MDA and NEFA levels, hepatic TC and TG levels and mRNA and protein expressions of LXRα, SREBP-1c, and FAS(P<0.01);and decreased hepatic SOD activity(P<0.01). Compared with the model group, all Liuwei Jiangzhi Decoction groups shared improved liver lipid deposition and reduced steatosis degree, serum ALT and AST activities and MDA and NEFA levels, and hepatic TC and TG levels as well as LXRα, SREBP-1c, FAS mRNA and protein expressions(P<0.05, P<0.01), and increased hepatic SOD activity(P<0.05, P<0.01).CONCLUSION Liuwei Jiangzhi Decoction can treat NAFLD because of its efficacy in regulating fatty acid metabolism in the liver and reducing oxidative stress response mediated by the the inhibition of SREBP-1c-FAS signal pathway.

关 键 词：六味降脂汤 NAFLD 脂肪酸代谢 氧化应激 LXRΑ SREBP-1C FAS 

分 类 号：R285.5[医药卫生—中药学]