重庆医学2018，Vol.47Issue(17)：2279-2284,6.DOI:10.3969/j.issn.1671-8348.2018.17.007
渥曼青霉素通过Chemerin/CMKLR1途径抑制Kupffer细胞NLRP3的活性缓解小鼠非酒精性脂肪肝
Wortmannin inhibits the activity of NLRP3 in Kupffer cells through the Chemerin/CMKLR1 pathway and relieves nonalcoholic fatty liver in mice
摘要
Abstract
Objective To investigate the role and mechanism of inflammatory response of Kupffer cells induced by Chemerin in the progression of non-alcoholic fatty liver disease (NAFLD) in mice.Methods Wortmannin was used to treated on KCs which pre-treated with Chemerin in vitro for two hours,and treated on C57BL/6J mice which was fed with a high-fat die.Levels of cytokines in supernatant/serum were tested by enzyme-linked immunosorbent assays(ELISA);mRNA and protein levels of KCs' Chemokine-like receptor 1 (CMKLR) and nucleotide oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) in vivo and vitrowere detected by real time polymerase chain reaction(real time-PCR) and Western blot;changes of mouse weight were recorded;insulin resistance and glucose tolerance were detected;the severity of liver steatosis was evaluated by HE staining combined with NAS score.Results The levels of interleukin 1β (IL-1β) and IL-18 in the KCs and mice treated with wortmannin were significantly lower than the KCs treated with Chemerin only and mice fed with high fat diet only.The mRNA and protein levels of CMKLR1 and inflammasome 3 (NLRP3) were significantly lower in the KCs and mice treated with Wortmannin than the KCs treated with Chemerin only and mice fed with high fat diet only.In addition,changes in mouse weight,hepatic steatosis,liver function,insulin resistance and glucose tolerance were much milder in mice treated with Wortmannin than those mice fed with high fat diet.Conclusion Wortmannin alleviates liver steatosis and inflammation mediated by KCs via down-regulating the expression of CMKLR1 and NLRP3 in high fat diet fed mice.关键词
非酒精性脂肪肝/枯否细胞/渥曼青霉素/炎症小体/ChemerinKey words
non-alcoholic fatty liver disease/Kupffer cells/Wortmannin/NLRP3/Chemerin分类
医药卫生引用本文复制引用
吴明兵,张文锋,龚建平,苗春木..渥曼青霉素通过Chemerin/CMKLR1途径抑制Kupffer细胞NLRP3的活性缓解小鼠非酒精性脂肪肝[J].重庆医学,2018,47(17):2279-2284,6.基金项目
国家自然科学基金资助项目(81701957) （81701957）
重庆卫生和计划生育委员会科技项目(2015-2-126). （2015-2-126）
