右美托咪定缓解脓毒症引起的心脏功能障碍的机制研究  

Study on the Mechanism of Metomipramine in Alleviating Cardiac Dysfunction Caused by Septicemia

作　　者：于杰 姚刚 赵岚 林生 YU Jie;YAO Gang;ZHAO Lan;LIN Sheng(The Second Department of Cardiovascular Medicine,Yantaishan Hospital of East Hospital,Yantai 264003,Shandong,China)

机构地区：[1]烟台山医院东院心血管内二科,山东烟台264003

出　　处：《医学信息》2023年第6期77-80,共4页Journal of Medical Information

基　　金：山东省医药卫生科技发展计划项目(编号:2016WS0697)。

摘　　要：目的探究右美托咪定(DEX)缓解脓毒症引起大鼠心功能障碍的机制。方法选择体重180~220 g的健康雄性SD大鼠30只,随机分为空白组(CON组)、模型组(CLP组)以及DEX干预组(DEX组),各10只。通过盲肠结扎穿孔术(CLP)建立脓毒症模型,DEX组于术后12 h腹腔注射DEX,CON组腹腔注射等量灭菌生理盐水。处理后,记录各组大鼠血流动力学参数,检测心功能,采用Elisa法检测血清中IL-6、IL-1β水平,采用酶联免疫吸附法检测大鼠血清中肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)的含量,Western blot法检测心肌组织中NLRP3炎症小体、Caspase-1、IL-1β蛋白表达水平。结果与CON组相比,CLP组和DEX组血清中IL-6、IL-1β、CK-MB以及LDH水平均有所升高,心脏血流动力学指标均有所下降(P<0.05);与CLP组比较,DEX组血清中IL-6、IL-1β、CK-MB以及LDH水平均有所下降,心肌组织中NLRP3、caspase-1、IL-1β蛋白表达水平下降(P<0.05);与CLP组比较,DEX组心脏血流动力学指标有所改善(P<0.05)。结论右美托咪定对脓毒症大鼠引起的心脏功能障碍以及心肌损伤具有一定的疗效,其机制可能与抑制NLRP3炎症小体激活,进而抑制下游炎症信号通路,减轻炎症,保护心肌组织免于损伤有关。Objective To explore the mechanism of dexmedetomidine(DEX)in alleviating cardiac dysfunction induced by sepsis in rats.Methods Thirty healthy male SD rats weighing 180-220 g were randomly divided into blank group(CON group),model group(CLP group)and DEX intervention group(DEX group),with 10 rats in each group.The sepsis model was established by cecal ligation and puncture(CLP).The DEX group was intraperitoneally injected with DEX at 12 h after operation,and the CON group was intraperitoneally injected with the same amount of sterile saline.After treatment,the hemodynamic parameters of rats in each group were recorded,and the cardiac function was detected.The levels of IL-6 and IL-1βin serum were detected by Elisa method.The contents of creatine kinase isoenzyme(CK-MB)and lactate dehydrogenase(LDH)in serum were detected by enzyme-linked immunosorbent assay.The expression levels of NLRP3 inflammasome,Caspase-1 and IL-1βprotein in myocardial tissue were detected by Western blot.Results Compared with the CON group,the serum levels of IL-6,IL-1β,CK-MB and LDH in the CLP group and the DEX group were increased,and the cardiac hemodynamic indexes were decreased(P<0.05).Compared with CLP group,the levels of IL-6,IL-1β,CK-MB and LDH in serum of DEX group decreased,and the expression levels of NLRP3,caspase-1 and IL-1βin myocardial tissue decreased(P<0.05).Compared with the CLP group,the hemodynamic parameters of the DEX group were improved(P<0.05).Conclusion Dexmedetomidine has a certain effect on cardiac dysfunction and myocardial injury induced by sepsis in rats,and its mechanism may be related to inhibiting the activation of NLRP3 inflammasome,inhibiting downstream inflammatory signal pathway,reducing inflammation and protecting myocardial tissue from injury.

关 键 词：右美托咪定 脓毒症 心脏功能障碍 心肌损伤 炎症 NLRP3 

分 类 号：R614[医药卫生—麻醉学] R459.7[医药卫生—外科学]