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活血化瘀方通过调节大鼠脂质代谢和氧化应激治疗非酒精性肝脂肪变性的机制

Mechanism of Huo-Xue-Qu-Yu Formula in Treating Nonalcoholic Hepatic Steatosis by Regulating Lipid Metabolism and Oxidative Stress in Rats.

作者信息

Cheng Bin, Zhou Ai-Zhen, Ge Wen, Yao Xiao-Min, Wang Juan

机构信息

School of Chinese Materia Medica, Zhejiang Pharmaceutical College, Ningbo 310053, China.

Institute of Biopharmaceutical, Zhejiang Pharmaceutical College, Zhejiang, Ningbo 315100, China.

出版信息

Evid Based Complement Alternat Med. 2021 Apr 29;2021:6026319. doi: 10.1155/2021/6026319. eCollection 2021.

Abstract

Huo-Xue-Qu-Yu formula (HXQYF) is a prescription consisting of leaf and Pall. for treating hyperlipidemia and NAFLD in China. Here, we investigated the hepatic and renal function, oxidative stress and lipid metabolism, and potential mechanisms of HXQYF on nonalcoholic fatty liver disease (NAFLD) rat models. NAFLD rat models were induced with high-fat diet (HFD) and 10% fructose water for 18 weeks and orally administered with or without HXQYF simultaneously. The results showed that HXQYF (22.5, 45, 90 mg/kg) significantly improved blood lipid levels reducing serum TC, TG, LDL-C, and APOB values and elevating HDL-C and APOA1 levels in NAFLD rats. The higher levels of ALT, AST, CR, and BUN in serum induced by HFD were reduced by HXQYF. HE staining showed that HXQYF (90 mg/kg) reduced the accumulation of fat droplets and alleviated inflammatory response in liver cells. Three doses of HXQYF exhibited notable antioxidant effects by elevating SOD, GSH, and CAT activities and decreasing MDA and OH-1 levels in the liver. Furthermore, abnormal lipid metabolism caused by HFD was alleviated by HXQYF, which was associated with the upregulation of PPAR-, AdipoR2, and CPT1 mRNAs as well as the downregulation of CYP2E1 and SREBP-1c mRNAs in liver tissue. In conclusion, our work verified that HXQYF could reduce the degree of hepatic steatosis, suppress oxidative stress, and attenuate lipid metabolism, thus preventing NAFLD.

摘要

活血祛瘀方(HXQYF)是一种在中国用于治疗高脂血症和非酒精性脂肪性肝病(NAFLD)的方剂,由叶和Pall.组成。在此,我们研究了HXQYF对非酒精性脂肪性肝病(NAFLD)大鼠模型的肝脏和肾脏功能、氧化应激和脂质代谢及其潜在机制。采用高脂饮食(HFD)和10%果糖水诱导NAFLD大鼠模型18周,并同时给予或不给予HXQYF口服。结果表明,HXQYF(22.5、45、90mg/kg)显著改善了NAFLD大鼠的血脂水平,降低了血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)和载脂蛋白B(APOB)值,提高了高密度脂蛋白胆固醇(HDL-C)和载脂蛋白A1(APOA1)水平。HXQYF降低了HFD诱导的血清中较高水平的谷丙转氨酶(ALT)、谷草转氨酶(AST)、肌酐(CR)和尿素氮(BUN)。苏木精-伊红(HE)染色显示,HXQYF(90mg/kg)减少了肝细胞内脂肪滴的积累,减轻了炎症反应。HXQYF的三个剂量通过提高肝脏中超氧化物歧化酶(SOD)、谷胱甘肽(GSH)和过氧化氢酶(CAT)的活性,降低丙二醛(MDA)和羟自由基(OH-1)水平,表现出显著的抗氧化作用。此外,HXQYF减轻了HFD引起的脂质代谢异常,这与肝组织中过氧化物酶体增殖物激活受体-(PPAR-)、脂联素受体2(AdipoR2)和肉碱棕榈酰转移酶1(CPT1)mRNA的上调以及细胞色素P450 2E1(CYP2E1)和固醇调节元件结合蛋白-1c(SREBP-1c)mRNA的下调有关。总之,我们的研究证实HXQYF可以减轻肝脏脂肪变性程度,抑制氧化应激,减弱脂质代谢,从而预防NAFLD。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1feb/8102110/ef59d8891523/ECAM2021-6026319.001.jpg

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