摘要
目的:探讨黄芩素调节过氧化物酶体增殖物激活型受体γ(PPARγ)/肝X受体α(LXRα)/三磷酸腺苷结合盒转运体A1(ABCA1)信号通路对非酒精性脂肪肝(NAFLD)大鼠肝功能和胰岛素抵抗的影响。方法:通过高脂饲料喂养建立NAFLD大鼠模型,将造模后的大鼠随机分为模型组、双酚A-二甘氨酸醚(BADGE)组(PPARγ抑制剂,20 mg·kg^(-1)BADGE)、黄芩素组(50 mg·kg^(-1)黄芩素)、黄芩素+BADGE组(50 mg·kg^(-1)黄芩素+20 mg·kg^(-1)BADGE),10只/组,另取10只大鼠作为对照组。检测各组大鼠甘油三酯(TG)、总胆固醇(TC)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、空腹胰岛素(FINS)、空腹血糖(FPG)水平,计算胰岛素抵抗指数(HOMA-IR);苏木精-伊红(HE)染色观察肝脏病理状况;油红O染色检测肝脏脂质沉积情况;TUNEL染色测定肝细胞凋亡情况;蛋白免疫印迹(western blot)法检验肝组织中通路相关蛋白表达水平。结果:模型组与对照组相比,大鼠肝组织损伤严重,TC、TG、FINS、FPG、ALT、AST水平、NAS积分、脏器指数、HOMA-IR均显著增加(P<0.05),PPARγ、LXRα、ABCA1蛋白表达均降低(P<0.05)。与模型组相比,黄芩素组病理损伤得到改善,细胞凋亡明显减少,TC、TG、FINS、FPG、ALT、AST水平、NAS积分、脏器指数、HOMA-IR均显著下降(P<0.05),PPARγ、LXRα、ABCA1蛋白表达均增加(P<0.05);BADGE组大鼠细胞凋亡明显增多,TC、TG、FINS、FPG、ALT、AST水平、NAS积分、脏器指数、HOMA-IR均显著升高(P<0.05),PPARγ、LXRα、ABCA1蛋白表达均降低(P<0.05)。BADGE逆转了黄芩素对NAFLD大鼠的保护作用。结论:黄芩素可通过激活PPARγ/LXRα/ABCA1信号通路,改善NAFLD大鼠肝功能受损和糖脂代谢异常,减轻胰岛素抵抗。
Objective: To investigate the effects of baicalein on liver function and insulin resistance of non-alcoholic fat Liver(NAFLD) rats through regulation of peroxisome proliferator-activated receptor γ(PPARγ)/liver X receptor α(LXRα)/ATP binding box transporter A1(ABCA1) signaling pathway. Methods: NAFLD rat model was established by feeding high-fat diet, and the rats were randomly divided into model group, bisphenol A-diglycine ether(BADGE) group(PPARγ inhibitor, 20 mg·kg^(-1)BADGE), baicalein group(50 mg·kg^(-1)baicalein), baicalein+BADGE group(50 mg·kg^(-1)baicalein+20 mg·kg^(-1)BADGE), 10 rats in each group, and another 10 rats were allocated into control group. The levels of triglyceride(TG), total cholesterol(TC), alanine aminotransferase(ALT), aspartate aminotransferase(AST), fasting insulin(FINS), and fasting blood glucose(FPG) of rats in each group were detected, and the insulin resistance index(HOMA-IR) was calculated;Hematoxylin-Eosin(HE) staining was performed to observe liver pathology;Oil red O staining was performed to measure liver lipid deposition;TUNEL staining was performed to measure liver cell apoptosis;Western blot method was performed to test the expression levels of related protein in liver tissues. Results: Compared with the control group, the liver tissue injury of model group was serious, the levels of TC, TG, FINS, FPG, ALT, AST, NAS score, Organ index and HOMA-IR were significantly increased(P<0.05), and the protein expressions of PPARγ, LXRα and ABCA1 were decreased(P<0.05). Compared with model group, baicalin group had improved pathological injury, decreased apoptosis, decreased TC, TG, FINS, FPG, ALT, AST, NAS score, Organ index and HOMA-IR significantly(P<0.05), and increased protein expression of PPARγ, LXRα and ABCA1(P<0.05);apoptosis of rats in the BADGE group was obviously increased, the levels of TC, TG, FINS, FPG, ALT, AST, NAS score, Organ index and HOMA-IR all increased obviously(P<0.05), and the expression of PPARγ, LXRα, and ABCA1 proteins all decreased(P<0.05). The protective effect of baicalin on NAFLD rats was reversed by BADGE. Conclusion: Baicalein can ameliorate the impaired liver function and abnormal glucose and lipid metabolism, and reduce insulin resistance in NAFLD rats by activating the PPARγ/LXRα/ABCA1 signaling pathway.
作者
王亮
刘安宁
李红玲
郑宽勇
王亚兰
陈利灵
WANG Liang;LIU Anning;LI Hongling;ZHENG Kuanyong;WANG Yalan;CHEN Liling(Department of Endocrinology,Xiantao First People's Hospital Affiliated to Yangtze University,Xiantao 433000,China;Department of Geriatrics,Xiantao First People's Hospital Affiliated to Yangtze University,Xiantao 433000,China)
出处
《现代医学》
2023年第1期17-23,共7页
Modern Medical Journal
基金
2022年度仙桃市第一人民医院院级科研项目(XXY2022002)
