Wortmannin inhibits the activity of NLRP3 in Kupffer cells through the Chemerin/CMKLR1 pathway and relieves nonalcoholic fatty liver in mice / 重庆医学

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.

Research progress of autophagy and its effect on acute pancreatitis / 国际外科学杂志

Acute pancreatitis (AP) is activated trypsin-induced pancreatic and its peripheral tissue inflammation caused by their own digestion.The activation in advance of trypsinogen and the inflammation cascade in pancreatic acinar cells are thought to be a key mechanism of the onset and development of AP.Autophagy pathway acting as Ⅱ type of programmed cell death occurs in the early pathological course of AP,blockade of which contributes to aggravating necrosis of acinar cells in AP.This article mainly discussed the recent advances in the understanding of autophagy researches and its function in the mechanism of AP.