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小檗碱通过激活 SIRT3/AMPK/ACC 通路改善高脂饮食诱导的大鼠非酒精性脂肪肝病。

Berberine Ameliorates High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Rats via Activation of SIRT3/AMPK/ACC Pathway.

机构信息

School of Traditional Chinese Medicine, Guangzhou, 510632, China.

Department of Traditional Chinese Medicine, the First Affiliated Hospital of Jinan University, Guangzhou, 510630, China.

出版信息

Curr Med Sci. 2019 Feb;39(1):37-43. doi: 10.1007/s11596-019-1997-3. Epub 2019 Mar 13.

DOI:10.1007/s11596-019-1997-3
PMID:30868489
Abstract

This study aimed to verify the effects of berberine (BBR) on the fat metabolism proteins involved in the sirtuin 3 (SIRT3)/adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) pathway in the liver tissues of rats with high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD). Forty-eight rats were randomly divided into the normal control (NC) group, HFD group or BBR group, with 16 rats in each group. After 8 and 16 weeks of treatment, serum and liver samples were collected. Subsequently, body parameters, biochemical parameters and liver pathology were examined. The expression levels of proteins involved in the SIRT3/AMPK/ACC pathway in the liver were detected by Western blotting. After 8 and 16 weeks of a HFD, the successful establishment of rat models with different degrees of NAFLD was confirmed by hematoxylin and eosin (H&E) and Oil Red O staining. NAFLD rat models exhibited obesity and hyperlipidemia, and the protein expression levels of SIRT3, p-AMPK, p-ACC, and CPT-1A in the liver were significantly decreased compared to those in the NC group. The concurrent administration of BBR with the HFD effectively improved serum and liver lipid profiles and ameliorated liver injury. Furthermore, the protein expression levels of SIRT3, p-AMPK, p-ACC, and CPT-1A in the liver were significantly increased in the BBR group as compared with those in the HFD group. In conclusion, our data suggest that the mechanism by which BBR ameliorates HFD-induced hepatic steatosis may be related to the activation of the SIRT3/AMPK/ACC pathway in the liver.

摘要

本研究旨在验证小檗碱(BBR)对高脂肪饮食(HFD)诱导的非酒精性脂肪肝病(NAFLD)大鼠肝脏组织中涉及沉默调节蛋白 3(SIRT3)/腺苷 5'-单磷酸(AMP)激活的蛋白激酶(AMPK)/乙酰辅酶 A 羧化酶(ACC)通路的脂肪代谢蛋白的影响。48 只大鼠随机分为正常对照组(NC)、HFD 组或 BBR 组,每组 16 只。治疗 8 周和 16 周后,采集血清和肝脏样本。随后,检查了体参数、生化参数和肝脏病理。通过 Western blot 检测肝脏中 SIRT3/AMPK/ACC 通路相关蛋白的表达水平。HFD 喂养 8 周和 16 周后,通过苏木精和伊红(H&E)和油红 O 染色证实了不同程度 NAFLD 大鼠模型的成功建立。NAFLD 大鼠模型表现出肥胖和高脂血症,与 NC 组相比,肝脏中 SIRT3、p-AMPK、p-ACC 和 CPT-1A 的蛋白表达水平明显降低。与 HFD 同时给予 BBR 可有效改善血清和肝脏脂质谱并改善肝损伤。此外,与 HFD 组相比,BBR 组肝脏中 SIRT3、p-AMPK、p-ACC 和 CPT-1A 的蛋白表达水平显著增加。综上所述,我们的数据表明,BBR 改善 HFD 诱导的肝脂肪变性的机制可能与肝脏中 SIRT3/AMPK/ACC 通路的激活有关。

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The role of mitochondrial sirtuins in health and disease.线粒体去乙酰化酶在健康与疾病中的作用。
Free Radic Biol Med. 2016 Nov;100:164-174. doi: 10.1016/j.freeradbiomed.2016.04.197. Epub 2016 May 6.
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Berberine Ameliorates Hepatic Steatosis and Suppresses Liver and Adipose Tissue Inflammation in Mice with Diet-induced Obesity.
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J Pharm Anal. 2025 Jan;15(1):101052. doi: 10.1016/j.jpha.2024.101052. Epub 2024 Aug 5.
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Advances in the pharmacological mechanisms of berberine in the treatment of fibrosis.黄连素治疗纤维化的药理机制研究进展
Front Pharmacol. 2024 Sep 20;15:1455058. doi: 10.3389/fphar.2024.1455058. eCollection 2024.
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