补气消脂方调控PI3K/AKT/mTOR通路改善自噬减轻小鼠非酒精性脂肪肝机制研究  

Mechanism of Buqi Xiaozhi Formula in alleviating non-alcoholic fatty liver in mice by improving autophagy via regulating the PI3K/AKT/mTOR pathway

作　　者：黄兰蔚 王瑞华 王宇 侯立新 平键[2,3] 李爽 HUANG Lanwei;WANG Ruihua;WANG Yu;HOU Lixin;PING Jian;LI Shuang(Department of Gastroenterology,Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai 201999,China;Central Laboratory,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shang-hai 201203,China;Key Laboratory of Liver and Kidney Diseases(Ministry of Education),Shanghai 201203,China)

机构地区：[1]上海市宝山区中西医结合医院消化科,上海201999 [2]上海中医药大学附属曙光医院实验中心,上海201203 [3]肝肾疾病病证教育部重点实验室,上海201203

出　　处：《中国医院药学杂志》2025年第3期241-246,共6页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金青年项目(编号:82305099);上海市宝山区医学重点学(专)科及特色品牌建设项目(编号:BSZK-2023-BZ07);上海市宝山区中西医结合医院优秀青年专家培养项目(编号:2022BY001)。

摘　　要：目的:围绕磷酸肌醇3-激酶(phosphoinositide 3-kinase,PI3K)/蛋白激酶B(protein kinase,AKT)/动物雷帕霉素靶蛋白(mechanistic target of rapamycin,mTOR)信号通路和自噬研究补气消脂方对高脂饮食诱导的非酒精性脂肪肝(nonalcoholic fatty liver disease,NAFLD)的干预作用及其可能机制。方法:采用高脂饮食16周,诱导NAFLD小鼠模型,于第13~16周以补气消脂方和易善复灌胃,检测血清肝功能、血脂及炎性细胞因子水平,HE和油红O染色观察肝组织病理形态学,测定肝组织血脂和脂质过氧化损伤指标,Western blot法检测脂肪代谢、自噬以及PI3K/AKT/mTOR相关蛋白表达水平。结果:补气消脂方降低NAFLD模型小鼠肝功能丙氨酸氨基转移酶和谷氨酸氨基转移酶活性,降低甘油三酯、胆固醇、低密度脂蛋白水平,改善肝组织炎症损伤和脂滴堆积,降低肝组织三酰甘油、胆固醇和游离脂肪酸含量,提高超氧化物歧化酶、谷胱甘肽过氧化物酶活性,降低丙二醛含量;下调脂质代谢相关蛋白乙酰辅酶A羧化酶,脂肪酸合成酶表达,上调肉碱棕榈酰转移酶蛋白表达,上调自噬标志物LC3表达,降低自噬底物P62表达,下调PI3K/AKT/mTOR信号通路蛋白表达水平。结论:补气消脂方可有效防治高脂饮食诱导的NAFLD形成,其机制与下调PI3K/AKT/mTOR信号通路改善自噬有关。OBJECTIVE To investigate the potential mechanisms of Buqi Xiaozhi Formula in the prevention and treatment of high-fat diet-induced non-alcoholic fatty liver disease(NAFLD)and the involvement of the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/mechanistic target of rapamycin(mTOR)signaling pathway and autophagy.METHODS A NAFLD mouse model was created by 16 weeks of high-fat diet.From weeks 13 to 16,oral gavage of Buqi Xiaozhi Formula and polyene phosphatidylcholine(Essentiale forte)was given.Serum liver function,blood lipids,and inflammatory cytokine levels were measured.Hematoxylin and eosin(H&E)and Oil Red O(ORO)staining were used to observe liver tissue morphology.Lipids and lipid peroxidation indicators in liver tissue were also determined.Western blot was used to detect the protein levels of proteins related to fat metabolism,autophagy,and the PI3K/AKT/mTOR pathway.RESULTS Buqi Xiaozhi Formula significantly reduced the activities of liver function enzymes(alanine aminotransferase and aspartate aminotransferase),blood triglycerides(TG),total cholesterol(TC),low-density lipoprotein(LDL)and malondialdehyde(MDA),but significantly increased activities of superoxide dismutase(SOD)and glutathione peroxidase(GPx)in the NAFLD mice.Buqi Xiaozhi Formula significantly downregulated lipid metabolism-related protein acetyl-CoA carboxylase,fatty acid synthase,autophagy substrate P62 and proteins involved in the PI3K/AKT/mTOR signaling pathway,but significantly upregulated carnitine palmitoyl transferase,and autophagy marker LC3.CONCLUSION Buqi Xiaozhi Formula effectively prevents and treats high-fat diet-induced NAFLD by improving autophagy via inhibiting the PI3K/AKT/mTOR signaling pathway.

关 键 词：非酒精性脂肪肝 自噬 PI3K/AKT/mTOR通路 补气消脂方 

分 类 号：R285[医药卫生—中药学] R966[医药卫生—中医学]