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疏肝健脾方对非酒精性脂肪性肝病大鼠肝细胞中p38丝裂原活化蛋白激酶/核因子κB信号通路表达的影响

Effects of Shugan-Jianpi Recipe on the Expression of the p38 MAPK/NF-κB Signaling Pathway in the Hepatocytes of NAFLD Rats.

作者信息

Deng Yuanjun, Tang Kairui, Chen Runsen, Liu Yajie, Nie Huan, Wang Hong, Zhang Yupei, Yang Qinhe

机构信息

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

出版信息

Medicines (Basel). 2018 Sep 19;5(3):106. doi: 10.3390/medicines5030106.

Abstract

In traditional Chinese medicine, the Shugan-Jianpi recipe is often used in the treatment of nonalcoholic fatty liver disease (NAFLD). This study aimed to explore the mechanism of the Shugan-Jianpi recipe in relation to rats with NAFLD induced by a high-fat diet. Rats were randomly divided into eight groups: normal group (NG), model group (MG), low-dose Chaihu⁻Shugan⁻San group (L-CG), high-dose Chaihu⁻Shugan⁻San group (H-CG), low-dose Shenling⁻Baizhu⁻San group (L-SG), high-dose Shenling⁻Baizhu⁻San group (H-SG), low dose of integrated-recipes group (L-IG), and high dose of integrated-recipes group (H-IG). After 26 weeks, a lipid profile, aspartate, and alanine aminotransferases in serum were detected. The serum levels of inflammatory factors including interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) were analyzed using the enzyme linked immunosorbent assay (ELISA) method. Hepatic pathological changes were observed with hematoxylin-eosin (HE) and oil red O staining. The expression of the p38 mitogen-activated protein kinases (MAPK)/nuclear factor-κB (NF-κB) pathway was detected by quantitative real-time PCR and Western blotting. A pathological section revealed that NAFLD rats have been successfully reproduced. Compared with the model group, each treatment group had different degrees of improvement. The Shugan-Jianpi recipe can inhibit the serum levels of IL-1β, IL-6, and TNF-α in NAFLD rats. The expression of mRNA and a protein related to the p38 MAPK/NF-κB signaling pathway were markedly decreased as a result of the Shugan-Jianpi recipe. The Shugan-Jianpi recipe could attenuate NAFLD progression, and its mechanism may be related to the suppression of the p38 MAPK/NF-κB signaling pathway in hepatocytes.

摘要

在传统中医中,疏肝健脾方剂常用于治疗非酒精性脂肪性肝病(NAFLD)。本研究旨在探讨疏肝健脾方剂对高脂饮食诱导的NAFLD大鼠的作用机制。将大鼠随机分为八组:正常组(NG)、模型组(MG)、低剂量柴胡疏肝散组(L-CG)、高剂量柴胡疏肝散组(H-CG)、低剂量参苓白术散组(L-SG)、高剂量参苓白术散组(H-SG)、低剂量复方组(L-IG)和高剂量复方组(H-IG)。26周后,检测血清脂质谱、天冬氨酸和丙氨酸转氨酶。采用酶联免疫吸附测定(ELISA)法分析血清中白细胞介素(IL)-1β、IL-6和肿瘤坏死因子-α(TNF-α)等炎症因子水平。用苏木精-伊红(HE)和油红O染色观察肝脏病理变化。通过定量实时PCR和蛋白质印迹法检测p38丝裂原活化蛋白激酶(MAPK)/核因子-κB(NF-κB)通路的表达。病理切片显示成功复制了NAFLD大鼠模型。与模型组相比,各治疗组均有不同程度改善。疏肝健脾方剂可抑制NAFLD大鼠血清中IL-1β、IL-6和TNF-α水平。疏肝健脾方剂可使p38 MAPK/NF-κB信号通路相关的mRNA和蛋白表达明显降低。疏肝健脾方剂可减轻NAFLD进展,其机制可能与抑制肝细胞中p38 MAPK/NF-κB信号通路有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d762/6163402/91545fb7cb6d/medicines-05-00106-g001.jpg

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