黄芩素调节PPARγ/LXRα/ABCA1信号通路干预NAFLD大鼠肝功能和胰岛素抵抗研究-现代医学

黄芩素调节PPARγ/LXRα/ABCA1信号通路干预NAFLD大鼠肝功能和胰岛素抵抗研究

单位：1. 长江大学附属仙桃市第一人民医院内分泌科, 湖北仙桃 433000;
2. 长江大学附属仙桃市第一人民医院老年病科, 湖北仙桃 433000

关键词：黄芩素 NAFLD 肝功能胰岛素抵抗 PPARγ/LXRα/ABCA1信号通路

分类号：R285.5

出版年·卷·期（页码）：2023·51·第一期（17-23）

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.

参考文献：

[1] 张哲滔，车念聪，郑亚琳，等.菖蒲郁金汤化裁方对2型糖尿病合并非酒精性脂肪肝大鼠SREBP-1c表达和胰岛素抵抗的影响[J].北京中医药，2019，38(1)：17-21.
[2] 王文清，易文城，林拥华.hUC-MSCs下调HIF-1α及VEGF表达对NAFLD大鼠肝脏损伤的作用[J].中华细胞与干细胞杂志，2019，9(1)：35-39.
[3] ROMERO-GOMEZ M,ZELBER-SAGI S,TRENELL M.Treatment of NAFLD with diet,physical activity and exercise[J].J Hepatol,2017,67(4):829-846.
[4] 李妍，杨艳宇，刘婷婷，等.甜菊醇调控巨噬细胞ABCA1蛋白表达[J].食品与生物技术学报，2020，39(11)：88-95.
[5] 葛樯樯，王雪芬，宗磊，等.绞股蓝总皂苷对ApoE-/-动脉粥样硬化小鼠血管PPAR-γ/LXR-α/ABCA1信号通路的影响[J].浙江医学教育，2019，18(4)：47-50.
[6] 田硕，洪涛，张多，等.黄芩素的药理作用及分子机制的最新研究进展[J].黑龙江医药，2015，28(6)：1195-1199.
[7] 房昉，温伟波，万春平，等.健肝消脂方对非酒精性脂肪性肝病胰岛素抵抗,脂质沉积的影响及相关mRNA差异表达初步分析[J].云南中医学院学报，2019，42(2)：1-10.
[8] 顾培青，沈洪，朱磊，等.清肠化湿方对溃疡性结肠炎大鼠结肠组织PPAR-γ,NF-κB及MUC2,TFF3的影响[J].中国实验方剂学杂志，2017，23(3)：79-85.
[9] 徐薇涵，张立泽，李欣，等.黄芩素调控热休克蛋白70表达对溃疡性结肠炎大鼠的影响[J].中国临床药理学杂志，2020，36(1)：36-38.
[10] 张宇，王威巍，左国华，等.粪便细菌移植对非酒精性脂肪性肝病大鼠肝功能和脂代谢紊乱的影响[J].第三军医大学学报，2019，41(13)：1200-1205.
[11] ZHU X,YAO P,LIU J,et al.Baicalein attenuates impairment of hepatic lysosomal acidification induced by high fat diet via maintaining V-ATPase assembly[J].Food Chem Toxicol,2020,136:110990.
[12] SUN W,LIU P,WANG T,et al.Baicalein reduces hepatic fat accumulation by activating AMPK in oleic acid-induced HepG2 cells and high-fat diet-induced non-insulin-resistant mice[J].Food Funct,2020,11(1):711-721.
[13] XING Y,REN X,LI X,et al.Baicalein enhances the effect of acarbose on the improvement of nonalcoholic fatty liver disease associated with prediabetes via the inhibition of de novo lipogenesis[J].J Agric Food Chem,2021,69(34):9822-9836.
[14] 祝鑫红，姚平，姜纯杰，等.黄芩素对高脂诱导的肝细胞氧化损伤的保护效应[J].中华肝脏病杂志，2021，29(5)：462-467.
[15] SMITH G I,SHANKARAN M,YOSHINO M,et al.Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease[J].J Clin Invest,2020,130(3):1453-1460.
[16] TANG H,ZENG Q,TANG T,et al.Kaempferide improves glycolipid metabolism disorder by activating PPARγ in high-fat-diet-fed mice[J].Life Sci,2021,270:119133.
[17] GE C X,YU R,XU M X,et al.Betaine prevented fructose-induced NAFLD by regulating LXRα/PPARα pathway and alleviating ER stress in rats[J].Eur J Pharmacol,2016,5(770):154-164.

服务与反馈：

【文章下载】【发表评论】【查看评论】【加入收藏】

提示：您还未登录，请登录！点此登录