醛固酮通过 NLRP3 炎性小体在激活原代小鼠肝星状细胞和肝纤维化中的作用。

Role of aldosterone in the activation of primary mice hepatic stellate cell and liver fibrosis via NLRP3 inflammasome.

机构信息

Department of Emergency Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.

State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.

出版信息

J Gastroenterol Hepatol. 2020 Jun;35(6):1069-1077. doi: 10.1111/jgh.14961. Epub 2020 Jan 14.

DOI:10.1111/jgh.14961

PMID:31860730

Abstract

BACKGROUND AND AIMS

Emerging evidence suggests aldosterone (aldo) and NLRP3 inflammasome are important factors for HSC activation and liver fibrosis. However, the interaction between aldo and NLRP3 inflammasome in HSC activation and liver fibrosis remains largely unknown. The aim of this study is to investigate the relationship between aldo and NLRP3 inflammasome in liver fibrosis.

METHODS

Serum and liver specimens collected from 40 patients with or without liver fibrosis were used to test the level of aldo and NLRP3. Primary HSC isolated from C57BL/6 mice were treated with aldo, and the effects of aldo on NLRP3 inflammasome and HSC activation were detected in vitro. Two animal models were used to verify the effect of aldo on liver fibrosis in vivo: hyperaldosteronism model was established in wild-type and NLRP3 knockout (NLRP3 ) mice by micro-pump, and liver fibrosis mouse model was built by tetrachloromethane (CCl ).

RESULTS

Patients with liver fibrosis showed higher aldo levels and increased NLRP3 expression in liver. In vitro, aldo induced the activation of primary mouse HSCs by promoting the expression and assembly of NLRP3 inflammasome. In vivo, NLRP3 knockout could alleviate the liver fibrosis induced by aldo in mice. In addition, treatment with spironolactone (spi) could inhibit the NLRP3 expression, HSC activation, and liver fibrosis induced by CCl .

CONCLUSIONS

Aldo promotes the activation of HSCs and liver fibrosis through NLRP3 inflammasome relative pathways. Intervention of aldo and NLRP3 inflammasome-related pathways may provide a promising strategy for treatment of liver fibrosis.

摘要

背景与目的

新出现的证据表明，醛固酮（aldo）和 NLRP3 炎性小体是肝星状细胞（HSC）活化和肝纤维化的重要因素。然而，aldo 与 NLRP3 炎性小体在 HSC 活化和肝纤维化中的相互作用在很大程度上仍不清楚。本研究旨在探讨肝纤维化中aldo 与 NLRP3 炎性小体之间的关系。

方法

收集 40 例有或无肝纤维化患者的血清和肝组织标本，检测 aldo 和 NLRP3 的水平。从 C57BL/6 小鼠中分离原代 HSC，用 aldo 处理，检测 aldo 对 NLRP3 炎性小体和 HSC 活化的影响。建立了两种动物模型来验证aldo 对体内肝纤维化的影响：通过微量泵在野生型和 NLRP3 敲除（NLRP3）小鼠中建立高醛固酮血症模型，用四氯化碳（CCl）建立肝纤维化小鼠模型。

结果

肝纤维化患者的aldo 水平升高，肝组织中 NLRP3 表达增加。体外，aldo 通过促进 NLRP3 炎性小体的表达和组装诱导原代小鼠 HSC 的活化。体内，NLRP3 敲除可减轻 aldo 诱导的小鼠肝纤维化。此外，用螺内酯（spi）治疗可抑制 CCl 引起的 NLRP3 表达、HSC 活化和肝纤维化。