右美托咪定对心肌缺血再灌注小鼠的保护作用  

Protective effect of dexmedetomidine on myocardial ischemia-reperfusion mice

作　　者：胡振飞[1] 黄一丹[1] 戴晓雯[1] HU Zhen-fei;HUANG Yi-dan;DAI Xiao-wen(Department of Anesthesiology,The First Afiliated Hospital of Xinjiang Medical University,Urumqi83001l,Xinjiang Uygur Autonomous Region,China)

机构地区：[1]新疆医科大学第一附属医院麻醉科,新疆乌鲁木齐830011

出　　处：《中国临床药理学杂志》2024年第4期574-578,共5页The Chinese Journal of Clinical Pharmacology

基　　金：新疆维吾尔自治区自然科学基金资助项目(2019D01C324)。

摘　　要：目的 探讨右美托咪定预处理对心肌缺血再灌注小鼠的保护作用及Nod样受体蛋白3(NLRP3)炎性信号通路的影响。方法 将C57BL/6J小鼠随机分为假手术组(只穿线不结扎)、模型组(结扎冠状动脉左前降支后恢复)、阳性对照组(腹腔注射1 mg·kg^(-1)的曲美他嗪后建模)、右美托咪定组(腹腔注射20μg·kg^(-1)的右美托咪定后建模)、抑制药组(腹腔注射10 mg·kg^(-1)的NLRP3抑制药MCC950后建模),每组12只。再灌注24 h后进行心功能指标检测,用蛋白质印迹法检测心肌组织相关蛋白表达水平,用酶联免疫吸附测定(ELISA)法检测各组小鼠血清因子表达水平,用试剂盒法检测心肌组织抗氧化指标水平,用Tunel法检测各组细胞凋亡水平。结果 假手术组、模型组、阳性对照组、右美托咪定组、抑制药组心肌组织NLRP3蛋白表达水平分别为0.31±0.05、1.06±0.07、0.52±0.05、0.65±0.07和0.39±0.04;凋亡相关颗粒样蛋白(ASC)表达水平分别为0.27±0.08、0.88±0.09、0.46±0.05、0.59±0.07和0.34±0.04;肌酸激脢同工酶(CK-MB)水平分别为(25.64±2.94)、(102.08±7.04)、(49.61±7.70)、(60.86±5.24)和(63.24±5.38)U·L^(-1);白细胞介素-6(IL-6)水平分别为(104.78±10.73)、(231.54±15.56)、(158.20±16.54)、(165.10±14.77)和(141.17±14.08)pg·mL^(-1);Tunel阳性细胞率分别为(4.34±0.16)%、(25.98±1.58)%、(8.74±0.93)%、(11.06±1.07)%和(9.19±0.88)%。模型组与假手术组比较,右美托咪定组、抑制药组分别与模型组比较,上述指标在统计学上差异均有统计学意义(均P<0.05)。结论 右美托咪定预处理可能通过抑制NLRP3/ASC/caspase-1炎性通路,抑制炎性反应和心肌细胞凋亡预防缺血再灌注心肌损伤。Objective To investigate the protective effect of dexmedetomidine(Dex) pretreatment on myocardial ischemia-reperfusion mice and the effect of Nod-like receptor protein 3(NLRP3) inflammatory signaling pathway.Methods C57BL/6J mice were randomly divided into sham group(only threading without ligation),model group(recovery after ligation of left anterior descending coronary artery),positive group(modeling after intraperitoneal injection of 1 mg · kg^(-1) trimetazidine),Dex group(modeling after intraperitoneal injection of 20 μg · kg^(-1)dexmedetomidine),MCC950 group(modeling after intraperitoneal injection of 10 mg · kg^(-1) NLRP3 inhibitor MCC950),12 mice in each group.Cardiac function indexes were detected at 24 h after reperfusion,the expression level of related proteins in myocardial tissue was detected by Western blot,enzyme-linked immunosorbent assay(ELISA) was used to detect the expression level of serum factor,myocardial antioxidant index was detected by kit method,and apoptosis was detected by Tunel method.Results The NLRP3 protein expression levels of sham group,model group,positive group,Dex group and MCC950 group were 0.31±0.05,1.06±0.07,0.52±0.05,0.65±0.07 and 0.39±0.04,respectively;the expression levels of apoptosis-associated granuloid protein(ASC) were 0.27±0.08,0.88±0.09,0.46±0.05,0.59±0.07 and 0.34±0.04,respectively;CK-MB levels were(25.64±2.94),(102.08±7.04),(49.61±7.70),(60.86±5.24) and(63.24±5.38) U·L^(-1),respectively;IL-6 levels were(104.78±10.73),(231.54±15.56),(158.20±16.54),(165.10±14.77) and(141.17±14.08) pg·mL^(-1),respectively;Tunel positive cell rates were(4.34±0.16) %,(25.98±1.58) %,(8.74±0.93) %,(11.06±1.07) % and(9.19±0.88) %,respectively.Sham group were compared with model group;Dex group and MCC950 group were compared with model group,the above indexes were statistically significant(all P <0.05).Conclusion Dexmedetomidine preconditioning may prevent ischemia-reperfusion myocardial injury by inhibiting NLRP3/ASC/caspase-1 inflammatory pathway,inflammat

关 键 词：右美托咪定 心肌缺血再灌注 炎性反应 心功能 Nod样受体蛋白3/凋亡相关颗粒样蛋白/胱天蛋白酶-1通路 

分 类 号：R971[医药卫生—药品]