p38丝裂原活化蛋白激酶信号通路参与柴胡疏肝散和参苓白术散对非酒精性脂肪性肝炎大鼠肝细胞的抗炎作用。

p38 MAPK signal pathway involved in anti-inflammatory effect of Chaihu-Shugan-San and Shen-ling-bai-zhu-San on hepatocyte in non-alcoholic steatohepatitis rats.

作者信息

Yang QinHe, Xu YongJian, Feng GaoFei, Hu ChaoFeng, Zhang YuPei, Cheng ShaoBing, Wang YanPing, Gong XiangWen

机构信息

Department of Traditional Chinese Medicine, Medical College of Jinan University, 601 Huangpu Road West, Guangzhou, Guangdong, China, 510632.

Department of Pathophysiology, Medical College of Jinan University, 601 Huangpu Road West, Guangzhou, Guangdong, China, 510632.

出版信息

Afr J Tradit Complement Altern Med. 2013 Nov 2;11(1):213-21. doi: 10.4314/ajtcam.v11i1.34. eCollection 2014.

Abstract

BACKGROUND

Traditional Chinese Medicine (TCM), has over thousands-of-years history of use. Chaihu-Shugan-San (CSS), and Shen-ling-bai-zhu-San (SLBZS), are famous traditional Chinese herbal medicine formulas, which have been used in China, for the treatment of many chronic diseases.

MATERIALS AND METHODS

This study investigated the anti-inflammatory effects of CSS and SLBZS on signaling molecules involved in p38 mitogen-activated protein kinase (p38 MAPK), pathway on hepatocytes of non-alcoholic steatohepatitis (NASH), rats induced by high fat diet. SD male rats were randomly divided into 8 groups: negative control group, model control group, high (9.6g/kg/day)/low (3.2g/kg/day)-dose CSS group, high (30g/kg/day)/low (10g/kg/day)-dose SLBZS group, high (39.6g/kg/day)/low (13.2g/kg/day)-dose integrated group. The rats of NASH model were induced by feeding a high-fat diet. After 16, wks, Hepatocytes were isolated from 6, rats in each group by collagenase perfusion. The liver histopathological changes and serum inflammatory cytokines TNF-α, IL-6 were determined. The proteins of TLR4, phosphor-p38 MAPK and p38 MAPK involved in p38 MAPK signal pathway were assayed.

RESULTS

The statistical data indicated the NASH model rats reproduced typical histopathological features of NASH in human. CSS and SLBZS ameliorated lipid metabolic disturbance, attenuated NASH progression, decreased the levels of TNF-α and IL-6 in serum, as well as inhibited TLR4 protein expression, p38 MAPK phosphorylation, and activation of p38 MAPK. In conclusion, CSS and SLBZS might work as a significant anti-inflammatory effect on hepatocyte of NASH by inhibiting the activation of TLR4, p-p38 MAPK and p38 MAPK involved in p38 MAPK signal pathway.

CONCLUSION

To some extent, CSS and SLBZS may be a potential alternative and complementary medicine to protect against liver injury, alleviate the inflammation reaction, moderate NASH progression.

摘要

背景

中药有着数千年的使用历史。柴胡疏肝散(CSS)和参苓白术散(SLBZS)是著名的中药方剂,在中国已被用于治疗多种慢性病。

材料与方法

本研究调查了CSS和SLBZS对高脂饮食诱导的非酒精性脂肪性肝炎(NASH)大鼠肝细胞中参与p38丝裂原活化蛋白激酶(p38 MAPK)信号通路的信号分子的抗炎作用。将SD雄性大鼠随机分为8组:阴性对照组、模型对照组、高剂量(9.6克/千克/天)/低剂量(3.2克/千克/天)CSS组、高剂量(30克/千克/天)/低剂量(10克/千克/天)SLBZS组、高剂量(39.6克/千克/天)/低剂量(13.2克/千克/天)联合用药组。通过高脂饮食诱导NASH模型大鼠。16周后,通过胶原酶灌注从每组6只大鼠中分离肝细胞。测定肝脏组织病理学变化以及血清炎性细胞因子肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)。检测p38 MAPK信号通路中涉及的Toll样受体4(TLR4)、磷酸化p38 MAPK和p38 MAPK蛋白。

结果

统计数据表明,NASH模型大鼠再现了人类NASH典型的组织病理学特征。CSS和SLBZS改善了脂质代谢紊乱,减轻了NASH进展,降低了血清中TNF-α和IL-6的水平,同时抑制了TLR4蛋白表达、p38 MAPK磷酸化以及p38 MAPK的激活。总之,CSS和SLBZS可能通过抑制p38 MAPK信号通路中TLR4、磷酸化p38 MAPK和p38 MAPK的激活,对NASH大鼠肝细胞发挥显著的抗炎作用。

结论

在一定程度上,CSS和SLBZS可能是预防肝损伤、减轻炎症反应、缓解NASH进展的潜在替代和补充药物。

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