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调肝祛脂汤通过促进CGI-58和抑制NLRP3炎性小体表达对非酒精性脂肪性肝病炎症损伤的保护作用

Protective Effects of Tiaoganquzhi Decoction in Treating inflammatory Injury of Nonalcoholic Fatty liver Disease by Promoting CGI-58 and Inhibiting Expression of NLRP3 Inflammasome.

作者信息

Zhang Huicun, Gao Xiang, Chen Pengmin, Wang Hongbing

机构信息

Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China.

Beijing Institute of Chinese Medicine, Beijing, China.

出版信息

Front Pharmacol. 2022 May 2;13:851267. doi: 10.3389/fphar.2022.851267. eCollection 2022.

Abstract

Tiaoganquzhi Decoction (TGQZD) is a traditional Chinese herbal formulation demonstrated to be a clinically effective treatment for nonalcoholic fatty liver disease (NAFLD), although details concerning its clinical mechanism are poor. This study aimed to explore the mechanism of TGQZD on improvement of inflammatory damage and dyslipidemia caused by NAFLD through the CGI-58/ROS/NLRP3 inflammasome pathway. In our research, the protective effects of TGQZD on HFD-induced liver injury in rats and using lipopolysaccharide (LPS)+palmitate (PA)-stimulated HepG-2 cells model. Histological changes were evaluated by hematoxylin-eosin and Oil Red O staining. Inflammatory cytokines and protein expression were analyzed by ELISA, Real time PCR and western blotting. Liver function, blood lipids, free fatty acids (FFA), and reactive oxygen species (ROS) were determined by biochemical detection. Our results indicated that TGQZD exhibited anti-inflammatory activity, reduced the severity of NAFLD and ameliorated the pathological changes. Further, TGQZD improved liver function and lipid metabolism in NAFLD rats. TGQZD lowered serum aspartate aminotransferase, alanine aminotransferase, triglyceride, and total cholesterol levels. TGQZD suppressed the formulation of FFA and ROS. It also reduced the expression and release of the inflammatory cytokine interleukin-1β by promoting CGI-58 expression and inhibiting the expression of FFA, TNF-α, and the NLRP3 inflammasome induced by ROS. TGQZD exhibited anti-inflammatory effects via the CGI-58, ROS and NLRP3 inflammasome pathway and , respectively. Our findings demonstrated that TGQZD is a useful and effective therapeutic agent for treating NAFLD via promotion of CGI-58 to inhibit the expression of ROS-induced NLRP3 inflammasome.

摘要

调肝祛湿汤(TGQZD)是一种传统的中药配方,已被证明对非酒精性脂肪性肝病(NAFLD)具有临床疗效,但其临床机制的细节尚不清楚。本研究旨在通过CGI-58/ROS/NLRP3炎性小体途径探讨TGQZD改善NAFLD引起的炎症损伤和血脂异常的机制。在我们的研究中,观察了TGQZD对高脂饮食诱导的大鼠肝损伤以及脂多糖(LPS)+棕榈酸(PA)刺激的HepG-2细胞模型的保护作用。通过苏木精-伊红和油红O染色评估组织学变化。通过酶联免疫吸附测定(ELISA)、实时聚合酶链反应(Real time PCR)和蛋白质免疫印迹法分析炎性细胞因子和蛋白质表达。通过生化检测测定肝功能、血脂、游离脂肪酸(FFA)和活性氧(ROS)。我们的结果表明,TGQZD具有抗炎活性,降低了NAFLD的严重程度并改善了病理变化。此外,TGQZD改善了NAFLD大鼠的肝功能和脂质代谢。TGQZD降低了血清天冬氨酸转氨酶、丙氨酸转氨酶、甘油三酯和总胆固醇水平。TGQZD抑制了FFA和ROS的生成。它还通过促进CGI-58表达并抑制ROS诱导的FFA、肿瘤坏死因子-α(TNF-α)和NLRP3炎性小体的表达,减少了炎性细胞因子白细胞介素-1β的表达和释放。TGQZD分别通过CGI-58、ROS和NLRP3炎性小体途径发挥抗炎作用。我们的研究结果表明,TGQZD是一种通过促进CGI-58抑制ROS诱导的NLRP3炎性小体表达来治疗NAFLD的有效治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8727/9108379/d863ec951d44/fphar-13-851267-g001.jpg

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