α7nAChR-mediated Dexmedetomidine to Reduce Hepatic Ischemia-Reperfusion Injury in Rats
Objective To investigate whether alpha-7 nicotinic acetylcholine receptor (α7nAChR) mediated the protective effect of dexmedetomidine ( DEX) on liver tissue in hepatic ischemia-reperfusion injury ( HIRI) .Methods Male SD rats were randomly divided into eight groups:⑴ SHAM group,in which the rat liver was exposed but not subjected to hepatic ischemia;⑵ SHAM+DEX group,in which rats received intraperitoneal injection of DEX (25 μg/kg),followed by the same treatment as the SHAM group;⑶HIRI group and⑷HIRI+DEX group,in which rats received intraperitoneal injec-tion of normal saline (0.9％) or DEX (25μg/kg),respectively,followed by establishment of the HIRI model;⑸SHAM+DMSO group and⑹HIRI+DMSO group,in which rats were treated by intraperitoneal injection of DMSO,followed by the same treatment as the SHAM or HIRI group;⑺ HIRI+DEX+DMSO group and ⑻ HIRI+DEX+MLA group,in which rats were treated by intraperitoneal injection of DMSO or MLA (α7nAChR inhibitor;4 mg/kg),respectively,followed by the same treatment as the DEX+HIRI group.The HIRI model was established by subjecting rats to 1 h of hepatic ischemia fol-lowed by 6 h of reperfusion.HE staining was performed on liver tissue to observe pathological changes and quantify liver in-jury scores,and aspartate aminotransferase ( AST) and alanine aminotransferase ( ALT) were measured in blood collected from the ocular globe.Western blot was used to detect the expressions of α7nAChR,JAK2,p-JAK2,STAT3,and p-STAT3 in the ischemic liver tissue.Results Compared with the SHAM group,the SHAM+DEX group exhibited reduced histopathological damage in liver tissue,with a decrease in liver injury scores ( P<0.001),and decreased ALT ( P<0.01) and AST ( P<0.001) .Furthermore,the expressions of α7nAChR,p-JAK2,and p-STAT3 were all increased ( P<0.001) .However,the liver injury was further exacerbated after the application of the α7nAChR inhibitor in the DEX group ( P<0.01),leading to increased ALT (P<0.01) and AST (P<0.05).Concurrently,the expressions of α7nAChR,p-JAK2,and p-STAT3 were all lowered (P<0.001).Conclusion The cholinergic anti-inflammatory pathway involving α7nAChR partially mediates the protective effect of DEX on liver tissue in HIRI rats.
万方数据
维普
