摘要
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 study the protective effects of nuclear factor-κB inhibitor, pyrrolidine dithiocarbamate （PDTC）, on ventricular dilatation and heart failure induced by experimental myocardial ischemic injury in rats and its mechanisms. Methods High dose of isoprenaline （ISO） was used to induce experimental myocardial ischemic injury in rats. Seventy male Wistar rats were divided into three groups： control group （20 rats）, ISO group （30 rats） and ISO ＋ PDTC group （20 rats）. Myocardial pathomorphologic changes, NF-κB p65 activation, MCP-1 mRNA expression and serum MCP-1were investigated. Then ventricular dilatation and left ventricular （LV） function were assessed by echocardiography on day 14 of the experiment. Results Myocardial NF-κB was activated, and MCP-1 mRNA expression and serum MCP-1 increased markedly after myocardial ischemic injury induced by ISO （P 〈0.01 ）. PDTC inhibited the activation of myocardial NF-κB and significantly decreased myocardial MCP-1 mRNA expression （P 〈0. 01）, serum MCP-1（P 〈0.01 ） , myocardial inflammation and injury. On the other hand, PDTC delayed replacement of the damaged myocardium with gran- ulation tissue. On day 14 of the experiment, a marked decrease in left ventricular end-systolic dimension （LVESD） and a significant increase in percentage of ejection fraction were observed in ISO ＋ PDTC group com- pared with ISO group （P 〈 0. 05）. Conclusion The protective effects of PDTC on ventrieular dilatation and heart failure may mainly be acquired from the acute stage of heart injury, which mechanisms are probably associated with inhibited activation of myocardial NF-κB, decreased myocardial MCP-1 mRNA expression, serum MCP-1, lessened myocardial inflammation and injury.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2008年第22期2128-2131,共4页
Journal of Third Military Medical University
关键词
核因子-ΚB抑制剂
单核细胞趋化蛋白-1
心肌缺血性损伤
心室扩张
心衰
nuclear factor-κB inhibitor
monocyte chemoattractant protein-1
myocardial ischemic injury
ventricular dilatation
heart failure
