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目的研究核因子-κB(nuclear factor-κB,NF-κB)抑制剂——吡咯烷二硫代氨基甲酸盐(pyrrolidine dithiocar-bamate,PDTC)对异丙肾上腺素(isoprenaline,ISO)所致大鼠缺血性心肌损伤后心室扩张、心衰的防治作用及其作用机制。方法应用大剂量ISO建立大鼠缺血性心肌损伤模型。70只雄性Wistar大鼠利用随机数字表法分为3组:对照组20只,实验组(ISO组)30只,治疗组(ISO+PDTC组)20只。检查心肌病理形态学、心肌NF-κB激活情况、心肌单核细胞趋化蛋白-1(MCP-1)mRNA表达情况及血清MCP-1水平,并在实验第14天进行超声心动图检查,观察心室扩张及心功能变化情况。结果ISO所致大鼠缺血性心肌损伤后心肌NF-κB被激活,心肌MCP-1 mRNA表达增加(P<0.01),血清MCP-1增高(P<0.01);PDTC能够抑制NF-κB的激活,下调心肌MCP-1 mRNA的表达及血清MCP-1水平(P<0.01),减轻心肌炎症反应,减小心肌细胞损伤范围,但同时可导致肉芽组织替代受损心肌延迟;实验第14天,治疗组左心室收缩末期内径(LVESD)较实验组减小(P<0.05),射血分数(EF)优于实验组(P<0.05)。结论应用PDTC能够对心肌缺血性损伤后的心室扩张、心功能损害起到一定的防治作用,该作用可能主要得益于在心肌损伤急性期对心肌细胞的保护作用,其机制可能与抑制NF-κB的激活进而下调MCP-1的表达、减轻心肌炎症损伤有关。
Objective To investigate the effect of pyrrolidine dithiocar-bamate (PDTC) on isoproterenol (ISO) induced by a nuclear factor-κB inhibitor (NF-κB) Prevention and treatment of ventricular dilatation and heart failure after ischemic myocardial injury in rats and its mechanism. Methods A large dose of ISO was used to establish a model of ischemic myocardial injury in rats. Seventy male Wistar rats were divided into three groups according to the random number table: control group (20), experimental group (ISO group), and treatment group (ISO + PDTC group), 20. The pathomorphology of myocardium, the activation of myocardial NF-κB, the expression of MCP-1 mRNA and the level of serum MCP-1 in myocardium were examined. Echocardiography was performed on the 14th day of the experiment, Ventricular dilatation and changes in cardiac function. Results After myocardial ischemic injury induced by ISO, NF-κB was activated in myocardium, the expression of MCP-1 mRNA was increased (P <0.01) and MCP-1 was increased (P <0.01) (P <0.01), relieve myocardial inflammatory response, reduce the extent of myocardial cell damage, but at the same time can lead to the replacement of impaired myocardial granulation tissue delayed; the first 14 days The left ventricular end - systolic diameter (LVESD) in the treatment group was significantly lower than that in the experimental group (P <0.05). The ejection fraction (EF) was superior to the experimental group (P <0.05). Conclusion PDTC can prevent ventricular dilatation and cardiac dysfunction after myocardial ischemic injury. This effect may be mainly due to the protective effect of PDTC on myocardial cells in the acute phase of myocardial injury. The mechanism may be related to inhibiting NF The activation of -κB further down-regulates the expression of MCP-1 and relieves the myocardial inflammatory injury.