右美托咪定联合七氟醚对糖尿病小鼠心肌缺血/再灌注损伤的保护作用  

Protective effect of dexmedetomidine combined with sevoflurane on myocardial ischemia/reperfusion injury in diabetic mice

作　　者：金辉[1] 肖志博[1] 葛树胜 吴小精 尹顺花 李媛[1] JIN Hui;XIAO Zhi-bo;GE Shu-sheng;WU Xiao-jing;YIN Shun-hua;LI Yuan(Department of Anesthesiology,First Affiliated Hospital of Hainan Medical College,Haikou Hainan 570100,China;Department of Anesthesiology,Hainan Women and Children Medical Center,Haikou Hainan 570100,China)

机构地区：[1]海南医学院第一附属医院麻醉科,海南海口570100 [2]海南省妇女儿童医学中心麻醉科,海南海口570100

出　　处：《局解手术学杂志》2022年第12期1032-1039,共8页Journal of Regional Anatomy and Operative Surgery

基　　金：海南省自然科学基金青年基金项目(820QN397)。

摘　　要：目的探讨右美托咪定(Dex)联合七氟醚-后处理(Sev-postC)对糖尿病小鼠心肌缺血/再灌注损伤(MI/RI)的保护作用及其分子机制。方法体外实验:分别在低糖(LG)和高糖(HG)条件下培养H9c2心肌细胞,并诱导缺氧/复氧(H/R)损伤模型,给予细胞七氟醚(Sev)或七氟醚联合右美托咪定(Sev+Dex)处理。CCK-8检测心肌细胞存活能力;ELISA检测细胞乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB)、超氧化物歧化酶(SOD)、丙二醛(MDA)的水平;Western blot检测细胞中缺氧诱导因子-1α(HIF-1α)和巨噬细胞迁移抑制因子(MIF)的表达。在体动物实验:分别使用健康小鼠和2型糖尿病小鼠构建MI/RI模型,并给予小鼠Sev-postC或Sev-postC+Dex治疗。Western blot检测小鼠心脏组织中HIF-1α和MIF的表达;HE染色检测小鼠心肌组织损伤情况;ELISA检测小鼠血清LDH和CK-MB的水平,以及心肌组织SOD和MDA的水平。结果细胞实验结果显示,与LG-Control组相比,LG-H/R组细胞存活能力显著降低(P<0.01);与LG-H/R组相比,LG-Sev组细胞存活能力显著升高(P<0.01);与HG-Control组相比,HG-H/R组细胞存活能力显著降低(P<0.01);与HG-H/R组相比,HG-Sev组细胞存活能力无显著变化(P>0.05),HG-Sev+Dex组细胞存活能力则显著升高(P<0.01)。与HG-H/R组相比,HG-Sev组LDH、CK-MB、SOD和MDA水平无显著变化(P>0.05),HG-Sev+Dex组上述4项指标均具有显著变化(P<0.01)。与HG-H/R组相比,HG-Sev组HIF-1α和MIF的表达无显著变化(P>0.05),HG-Sev+Dex组HIF-1α的表达显著降低(P<0.01),MIF的表达显著升高(P<0.01)。小鼠模型研究结果显示,在糖尿病小鼠中,与DM-MI/RI组相比,DM-Sev-postC组小鼠HIF-1α和MIF的表达无显著变化(P>0.05),而DM-Sev-postC+Dex组小鼠HIF-1α表达显著降低(P<0.01),MIF的表达显著升高(P<0.01)。HE染色结果显示,与DM-MI/RI组相比,DM-Sev-postC组小鼠心肌损伤无明显缓解,而DM-Sev-postC+Dex组小鼠心肌损伤缓解十分显著。与DM-MI/RI组相比,仅DM-Sev-postC+Dex组Objective To explore the protective effect and the molecular mechanism of dexmedetomidine(Dex)combined with sevoflurane-post conditioning(Sev-postC)on myocardial ischemia/reperfusion injury(MI/RI)in diabetic mice.Methods In vitro experiments:H9c2 cardiomyocytes were cultured under low glucose(LG)and high glucose(HG)conditions respectively,hypoxia/reoxygenation(H/R)injury models were induced,and cells were treated with sevoflurane(Sev)or sevoflurane combined with dexmedetomidine(Sev+Dex).CCK-8 was used to detect the viability of cardiomyocytes.ELISA was used to detect the levels of lactate dehydrogenase(LDH),creative kinase isoenzyme MB(CK-MB),superoxide dismutase(SOD)and malondialdehyde(MDA)of cells.Western blot was used to detect the expressions of hypoxia inducible factor 1 subunit alpha(HIF-1α)and macrophage migration inhibitory factor(MIF)of cells.In vivo animal experiments:MI/RI models were constructed by using healthy mice and type 2 diabetic mice,respectively,and the mice were given Sev-postC or Sev-postC+Dex treatment.Western blot was used to detect the expression of HIF-1αand MIF in mouse heart tissue.HE staining was used to detect myocardial tissue damage in mice.ELISA was used to detect the serum LDH and CK-MB levels,as well as the SOD and MDA levels of myocardial tissues.Results The results of cell experiment showed that compared with the LG-Control group,the cell viability in the LG-H/R group was significantly reduced(P<0.01);compared with the LG-H/R group,the cell viability of the LG-Sev group was significantly increased(P<0.01);compared with the HG-Control group,the cell viability in the HG-H/R group was significantly reduced(P>0.05);compared with the HG-H/R group,the cell viability in the HG-Sev group was not significantly changed(P>0.05),while the cell viability in the HG-Sev+Dex group was significantly increased(P<0.01).Compared with the HG-H/R group,the levels of LDH,CK-MB,SOD and MDA in the HG-Sev group were not significantly changed(P>0.05);while the 4 above indicators in the HG-Sev+Dex gro

关 键 词：右美托咪定 七氟醚-后处理 糖尿病 心肌缺血/再灌注损伤 

分 类 号：R614[医药卫生—麻醉学]