α7nAChR介导右美托咪定减轻大鼠肝缺血再灌注损伤  

α7nAChR-mediated Dexmedetomidine to Reduce Hepatic Ischemia-Reperfusion Injury in Rats

作　　者：黄贺鑫 王贤裕[1] 蒙臣 HUANG Hexin;WANG Xian-yu;MENG Chen(Department of Anesthesiology,Taihe Hospital,Hubei University of Medicine,Shiyan,Hubei 442000,China)

机构地区：[1]湖北医药学院附属太和医院麻醉科,湖北十堰442000

出　　处：《湖北医药学院学报》2024年第6期618-622,F0002,共6页Journal of Hubei University of Medicine

基　　金：国家重点研发计划项目(2018YFC2001900);十堰市科学技术局项目(19Y28)。

摘　　要：目的:研究α7烟碱型乙酰胆碱受体(alpha7 nicotinic acetylcholine receptor,α7nAChR)是否介导了右美托咪定(dexmedetomidine,DEX)在肝缺血再灌注损伤(hepatic ischemia-reperfusion injury,HIRI)中的肝组织保护作用。方法:雄性SD大鼠随机分为8组,每组4只:⑴对照组(SHAM组),大鼠只暴露肝脏但不做肝缺血处理;⑵SHAM+DEX组,腹腔注射DEX(25μg/kg),之后处理同SHAM组;⑶HIRI组与⑷HIRI+DEX组,腹腔注射0.9%氯化钠溶液或DEX(25μg/kg),后建立HIRI模型;⑸SHAM+DMSO组与⑹HIRI+DMSO组,腹腔注射DMSO,之后处理同SHAM组或HIRI组;⑺HIRI+DEX+DMSO组与⑻HIRI+DEX+MLA组,腹腔注射DMSO或MLA(α7nAChR抑制剂;4 mg/kg),之后处理同DEX+HIRI组。先使大鼠肝脏缺血1 h,再灌注6 h,制作HIRI模型。行肝组织HE染色观察病理变化并行肝损伤评分,检测眼球血中谷草转氨酶(AST)、谷丙转氨酶(ALT)含量,用Western Blot检测缺血肝组织中的α7nAChR、JAK2、p-JAK2、STAT3、p-STAT3表达量。结果:与SHAM组相比,SHAM+DEX组的肝组织病理损伤明显减轻,肝损伤评分降低(P<0.001),ALT(P<0.01)与AST(P<0.001)含量显著减少,α7nAChR、p-JAK2、p-STAT3表达量均明显升高(P<0.001)。而使用α7nAChR抑制剂使DEX处理后的肝损伤再次加重(P<0.01),ALT(P<0.01)与AST(P<0.05)含量升高,α7nAChR、p-JAK2、p-STAT3的表达水平均显著降低(P<0.001)。结论:α7nAChR胆碱能抗炎通路部分介导了DEX对HIRI肝组织的保护作用。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:⑴SHAM group,in which the rat liver was exposed but not subjected to hepatic ischemia;⑵SHAM+DEX group,in which rats received intraperitoneal injection of DEX(25μg/kg),followed by the same treatment as the SHAM group;⑶HIRI group and⑷HIRI+DEX group,in which rats received intraperitoneal injection 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;⑺HIRI+DEX+DMSO group and⑻HIRI+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 injury 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 ofα7nAChR,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 ofα7nAChR,p-JAK2,and p-STAT3 were all increased(P<0001).However,the liver injury was further exacerbated after the application of theα7nAChR inhibitor in the DEX group(P<001),leading to increased ALT(P<0.01)and AST(P<0.05).Concurrently,the expressions ofα7nAChR,p-JAK2,and p-STAT3 were all lowered(P<0.001).Conclusion T

关 键 词：肝缺血再灌注损伤 右美托咪定 Α7烟碱型乙酰胆碱受体 STAT3 JAK2 

分 类 号：R614[医药卫生—麻醉学]