右美托咪定通过下调Dectin-1表达抑制免疫细胞浸润保护缺血/再灌注损伤的心肌  

Dexmedetomidine protects myocardium from ischemia/reperfusion injury by down regulating expression of Dectin-1 and inhibiting immune cells infiltration

作　　者：陈思宇[1] 吴建江[1] 李爱梅[1] 邓莉 胡振飞[1] 王江[1] CHEN Siyu;WU Jianjiang;LI Aimei;DENG Li;HU Zhenfei;WANG Jiang(Department of Anesthesiology,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China)

机构地区：[1]新疆医科大学第一附属医院麻醉科,乌鲁木齐830054

出　　处：《中国免疫学杂志》2024年第9期1843-1849,共7页Chinese Journal of Immunology

基　　金：新疆维吾尔自治区自然科学基金(2022D01C229)。

摘　　要：目的:探索右美托咪定(Dex)保护缺血/再灌注(I/R)诱导的心肌损伤的分子机制。方法:小鼠在体实验分组如下:野生型小鼠对照(Control)组、假手术(Sham)组、野生型小鼠缺血/再灌注模型(WT I/R)组和Dex预处理(WT Dex)组,Dectin-1基因敲除小鼠缺血/再灌注模型(KO I/R)组和Dex预处理(KO Dex)组,每组6只。TTC染色并测定小鼠心脏梗死区域(%),HE染色和病理学分析小鼠心肌损伤情况,ELISA测定小鼠血清TNF-α、IL-6和IL-10的水平,流式细胞术(FCM)计数和分选小鼠心肌浸润M2巨噬细胞和中性粒细胞,qPCR测定上述分选细胞中Dectin-1 mRNA表达情况。结果:TTC结果显示Control组和Sham组小鼠心肌未发生梗死;与WT I/R组相比,WT Dex组、KO I/R组和KO Dex组小鼠心肌梗死体积显著减少(P<0.05)。与KO I/R组相比,KO Dex组小鼠心肌梗死体积也明显减小(P<0.05)。HE染色结果显示WT I/R组小鼠心肌排列杂乱,出现大量断裂心肌纤维,WT Dex组、KO I/R组和KO Dex组小鼠心肌纤维存在少许断裂的情况,结构破坏不显著,心肌排列较为整齐;KO Dex组小鼠心肌损伤程度小于KO I/R组。ELISA结果显示,与Sham组相比,WT I/R组小鼠血清TNF-α和IL-6水平显著升高,IL-10水平显著降低;与WT I/R组相比,WT Dex组和KO I/R组小鼠血清TNF-α和IL-6水平显著降低,IL-10水平显著升高;与KO I/R组相比,KO Dex组小鼠血清TNF-α和IL-6水平显著降低,IL-10水平显著升高(P<0.05)。FCM结果显示,与Sham组相比,WT I/R组小鼠心肌浸润大量M2巨噬细胞和中性粒细胞(P<0.05);与WT I/R组相比,WT Dex组、KO I/R组和KO Dex组小鼠心肌浸润的M2巨噬细胞和中性粒细胞显著降低(P<0.05);KO I/R组和KO Dex组之间差异无统计学意义(P>0.05)。qPCR结果显示,与Sham组相比,WT I/R组小鼠心肌浸润的M2巨噬细胞和中性粒细胞中Dectin-1 mRNA表达量显著上调(P<0.05);与WT I/R组相比,Dex组则显著降低(P<0.05);KO I/R组和KO Dex组小鼠不表达Dectin-1。结论:Dex预处Objective:To explore the molecular mechanism of dexmedetomidine(Dex)protecting ischemia/reperfusion(I/R)myocardium.Methods:Wild type mice were grouped into control(Control)group,sham operation(Sham)group,WT I/R group,WT Dex group,and Dectin-1 knock out mice were grouped into KO I/R group and KO Dex group in the in vivo study(n=6).TTC staining was used to determine the myocardial infarction area(%)of the above six groups of mice.HE staining and pathological analyze was used to determine the myocardial injury.Serum TNF-α,IL-6 and IL-10 levels in mice were detected by ELISA.Flow cytometry(FCM)was used to count and sort of infiltrating M2 macrophages and neutrophils in myocardium.qPCR assay was used to determine the Dectin-1 mRNA expression in the above sorted cells.Results:TTC results showed that there was no myocardial infarction in the mice of Control group and Sham group.Compared with the WT I/R group,the infarct volume was significantly lower in WT Dex group,KO I/R group and KO Dex group(P<0.05).Compared with the KO I/R group,the infarct volume was reduced in KO Dex group(P<0.05).The results of HE staining showed that the myocardial fibers of the WT I/R group of mice were disorderly arranged,with a large number of broken myocardial fibers,while the myocardial fibers of the WT Dex group,KO I/R group and KO Dex group of mice had a little breakage,the structural damage was not significant,and the myocardial arrangement was relatively neat.The degree of myocardial injury of mice in KO Dex group were less than that in KO I/R group mice.ELISA results showed that compared with Sham group,the serum TNF-αand IL-6 levels of the mice in WT I/R group were significantly increased,and the IL-10 level was significantly decreased.Compared with WT I/R group,serum TNF-αand IL-6 levels of the mice in WT Dex group and KO I/R group were significantly decreased,and IL-10 level was significantly increased.Compared with KO I/R group,the serum TNF-αand IL-6 levels of the mice in KO Dex group were significantly decreased,and the IL-1

关 键 词：右美托咪定 心肌缺血/再灌注损伤 M2巨噬细胞 中性粒细胞 DECTIN-1 

分 类 号：R363[医药卫生—病理学]