新型合成化合物DIMO后处理对大鼠心肌缺血再灌注损伤的保护
发布时间：2018-12-28 09:27
【摘要】：目的观察新型合成化合物Z-甲基-5-(3,5-二甲氧基苯甲撑基)-2-亚氨-1-咪唑-4-酮(DIMO)是否对大鼠心肌缺血再灌注损伤具有保护作用,并且探究其发挥作用的信号通路。方法在体实验采用86只成年雄性SD大鼠建立急性大鼠在体心肌缺血再灌注(I/R)损伤模型。随机分为4组:假手术组(Sham组)、单纯缺血再灌注对照组(I/R组)、DIMO1mg/kg后处理组(DIMO-1组)、DIMO 2mg/kg后处理组(DIMO-2组)。除Sham组外,其余各组均缺血30 min,再灌注4 h。于再灌注4 h末,提取心脏,采用氯化三苯基四氮唑染色法(TTC法)测定心肌梗死范围;采用免疫印迹法(Western blot技术)检测Cathepsin B、Cathepsin L、Beclin-1、LC3Ⅱ/Ⅰ及P62蛋白表达水平;采用免疫共沉淀和Western blot检测RIP1K和RIP3K的相互作用。离体实验通过培养原代心肌细胞,通过氧糖剥夺(OGD)方法建立缺氧缺糖细胞模型。随机分为4组:对照组(non-OGD组)、对照给药组(non-OGD+DIMO组)、模型组(OGD/R组)、模型给药组(OGD/R+DIMO组)。OGD3h,复氧12h后,采用LDH漏出率检测心肌细胞损伤;Annexin-V和碘化丙啶(PI)双染色法检测心肌细胞的凋亡坏死率;免疫共沉淀和Western blot检测RIP1K和RIP3K的相互作用;采用Western blot检测Cathepsin B、Cathepsin L、Beclin-1、LC3Ⅱ/Ⅰ及P62蛋白表达水平。结果体内实验:与Sham组相比,I/R组心肌梗死范围增大,心肌细胞损伤增加,Cathepsin B、Cathepsin L、Beclin-1、LC3Ⅱ/Ⅰ及P62蛋白表达上调(P0.05),RIP1K表达上调(P0.05)。与I/R组比较,DIMO-1与DIMO-2组心肌梗死范围减小,心肌细胞损伤减少,Cathepsin B、Cathepsin L、Beclin-1、LC3Ⅱ/Ⅰ及P62蛋白表达下调(P0.05),RIP1K表达下调(P0.05)。体外实验:与non-OGD组比较,OGD/R组Cathepsin B、Cathepsin L、Beclin-1、LC3Ⅱ/Ⅰ及P62蛋白表达上调(P0.05),LDH漏出率和细胞凋亡坏死率增多(P0.05)。与OGD/R组比较,OGD/R+DIMO组Cathepsin B、Cathepsin L、Beclin-1、LC3Ⅱ/Ⅰ及P62蛋白表达下调(P0.05),LDH漏出率和细胞凋亡坏死率降低(P0.05)。结论新型合成化合物DIMO对大鼠在体心肌I/R损伤具有保护作用,其机制可能是通过作用于抑制坏死性凋亡及自噬水平,进而减少再灌注期间的心肌细胞死亡。
[Abstract]:Objective to investigate the protective effect of a new synthetic compound Z-methyl-5- (3O5-dimethoxybenzomethyl) -2-imidazole-4-one (DIMO) on myocardial ischemia-reperfusion injury in rats. And explore its role in the signal pathway. Methods 86 adult male SD rats were used to establish acute myocardial ischemia-reperfusion (I / R) injury model in vivo. They were randomly divided into four groups: sham operation group (Sham group), ischemia reperfusion control group (I / R group) and DIMO1mg/kg post treatment group (DIMO-1 group), DIMO 2mg/kg post treatment group (DIMO-2 group). With the exception of Sham group, all the other groups were subjected to ischemia for 30 min, and reperfusion for 4 h. At the end of 4 h after reperfusion, the heart was extracted and the myocardial infarction size was determined by triphenyl tetrazolium chloride staining (TTC), and the expression levels of Cathepsin Bon Cathepsin L, Beclin-1C 3 鈪，
本文编号：2393780
[Abstract]:Objective to investigate the protective effect of a new synthetic compound Z-methyl-5- (3O5-dimethoxybenzomethyl) -2-imidazole-4-one (DIMO) on myocardial ischemia-reperfusion injury in rats. And explore its role in the signal pathway. Methods 86 adult male SD rats were used to establish acute myocardial ischemia-reperfusion (I / R) injury model in vivo. They were randomly divided into four groups: sham operation group (Sham group), ischemia reperfusion control group (I / R group) and DIMO1mg/kg post treatment group (DIMO-1 group), DIMO 2mg/kg post treatment group (DIMO-2 group). With the exception of Sham group, all the other groups were subjected to ischemia for 30 min, and reperfusion for 4 h. At the end of 4 h after reperfusion, the heart was extracted and the myocardial infarction size was determined by triphenyl tetrazolium chloride staining (TTC), and the expression levels of Cathepsin Bon Cathepsin L, Beclin-1C 3 鈪，
本文编号：2393780
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