中医药干预炎症小体治疗非酒精性脂肪性肝炎的研究进展

Effect of Traditional Chinese Medicine on Prevention and Treatment of Nonalcoholic Steatohepatitis Via Interfering with Inflammasomes

非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)是组织学上以肝脂肪变性、炎细胞浸润或伴有间质纤维增生为主要病理特征的慢性肝脏疾病,为非酒精性脂肪性肝病的重要病理阶段。炎症小体是一类多蛋白复合体,也是先天性免疫的模式识别受体之一,能够识别病原体相关分子模式(PAMPs)和损伤相关分子模式(DAMPs),炎症小体受体蛋白被激活后可招募凋亡相关斑点样蛋白以进一步募集半胱氨酸天冬酶,释放炎症因子,从而诱发或加重炎症反应,损伤肝细胞。可见炎症小体在非酒精性脂肪性肝炎的发生发展中起关键作用。临床上运用中医药治疗NASH取得不错的疗效,而炎症小体是部分中药改善NASH的关键途径或靶点之一。目前与NASH发病关系较为密切的有NLRP3炎症小体和NLRP6炎症小体,这两者与中医药的关系值得进一步的研究。因此,基于NLRP3炎症小体和NLRP6炎症小体的靶向干预,围绕清热化湿、祛瘀化痰、补益肝肾的治法,概述中医药改善非酒精性脂肪性肝炎的作用机理研究进展,以期为NASH的进一步研究及临床治疗提供新的思路。

Nonalcoholic steatohepatitis(NASH) is a chronic liver disease histologically characterized by hepatic steatosis, inflammation or collagen deposition. It is an important pathological stage of nonalcoholic fatty liver disease(NAFLD). Inflammasomes are a class of polyprotein complexes and are one of the pattern recognition receptors for innate immunity. Inflammasomes can recognize pathogen-associated molecular patterns(PAMPs) and damage-associated molecular patterns(DAMPs) and then activate the inflammasomes receptor proteins. Afterward, apoptosis-associated speck-like protein is recruited to further recruit caspase, thereby inducing or aggravating inflammatory reactions and damage liver cells via releasing inflammatory factors. It can be seen that inflammasomes play a key role in the development of NASH. Clinically, traditional Chinese medicine has a good curative effect on the treatment of NASH, and inflammasomes are one of the key pathways or targets for some Chinese medicine to alleviate NASH. Currently, there are NLRP3 inflammasomes and NLRP6 inflammasomes closely related to NASH. The relationship between inflammasomes and traditional Chinese medicine deserves further study. Therefore, based on the targeted intervention of NLRP3 inflammasomes and NLRP6 inflammasomes, we focused on the principles and methods of treatment of clearing heat and dampness, removing stasis and resolving phlegm, tonifying liver and kidney in this paper. Meanwhile, we summarized the research progress about the mechanism of traditional Chinese medicine to improve NASH in order to provide new ideas for further research and clinical treatment of NASH.