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[糖尿病肾病中NLRP3炎性小体激活的分子调控机制及中药的干预作用]

[Molecular regulative mechanisms of NLRP3 inflammasome activation in diabetic nephropathy and interventional effects of Chinese herbal medicine].

作者信息

Wang Wen-Wen, Han Wen-Bei, Wan Yi-Gang, Tu Yue, Liu Bu-Hui, Liu Ying-Lu, Wu Wei, Yee Hong-Yun, Fang Qi-Jun, Yao Jian

机构信息

Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine Nanjing 210008, China Department of Nephrology,Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine Wenzhou 325000, China.

Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine Nanjing 210008, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2020 Jan;45(1):7-13. doi: 10.19540/j.cnki.cjcmm.20190618.402.

Abstract

The progression of renal damage in diabetic nephropathy(DN)is closely related to Nod-like receptor protein3(NLRP3)inflammasome activation. The characteristics of NLRP3 inflammasome activation include the changed expression and combination levels of NLRP3, apoptosis-associated speck-like protein(ASC)and pro-caspase-1, the increased expression levels of caspase-1, interleukin(IL)-1β and IL-18 and the excessive release levels of the relative inflammatory mediators. Its molecular regulative mechanisms involve the activation of multiple signaling pathways including reactive oxygen species(ROS)/thioredoxin-interacting protein(TXNIP)pathway, nuclear factor(NF)-κB pathway, nuclear factor erythroid-related factor 2(Nrf2)pathway, long non-coding RNA(lncRNA)pathway and mitogen-activated protein kinases(MAPKs)pathway. In addition, more importantly, never in mitosis aspergillus-related kinase 7(Nek7), as a kinase regulator, could target-combine with NLRP3 at upstream to activate NLRP3 inflammasome. Some extracts of Chinese herbal medicines(CHMs)such as quercetin, curcumin, cepharanthine, piperine and salidroside, as well as Chinese herbal compound prescriptions such as Wumei Pills both could treat NLRP3 inflammasome to ameliorate inflammatory renal damage in DN. Therefore, accurately clarifying the targets of anti-inflammatory CHMs and Chinese herbal compound prescriptions delaying DN progression by targeting the molecular regulative mechanisms of NLRP3 inflammasome activation will be one of the development directions in the future.

摘要

糖尿病肾病(DN)中肾损伤的进展与NOD样受体蛋白3(NLRP3)炎性小体激活密切相关。NLRP3炎性小体激活的特征包括NLRP3、凋亡相关斑点样蛋白(ASC)和前半胱天冬酶-1的表达和结合水平改变,半胱天冬酶-1、白细胞介素(IL)-1β和IL-18的表达水平升高以及相关炎症介质的过度释放。其分子调节机制涉及多种信号通路的激活,包括活性氧(ROS)/硫氧还蛋白相互作用蛋白(TXNIP)通路、核因子(NF)-κB通路、核因子红细胞相关因子2(Nrf2)通路、长链非编码RNA(lncRNA)通路和丝裂原活化蛋白激酶(MAPKs)通路。此外,更重要的是,有丝分裂后期促进复合物相关激酶7(Nek7)作为一种激酶调节剂,可在上游与NLRP3靶向结合以激活NLRP3炎性小体。一些中药提取物如槲皮素、姜黄素、千金藤素、胡椒碱和红景天苷,以及中药复方制剂如乌梅丸,均可作用于NLRP3炎性小体以改善DN中的炎性肾损伤。因此,通过靶向NLRP3炎性小体激活的分子调节机制,准确阐明抗炎中药及中药复方制剂延缓DN进展的靶点将是未来的发展方向之一。

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