大鼠缺血性心肌损伤后早期抑制核因子κB对心功能的影响  

Effects of inhibition of nuclear factor-κB early after myocardial ischemia on heart function in rats

作　　者：潘波[1] 古平[1] 童莉[1] 牟海刚[1] 戴静澜 杨成明[2] 

机构地区：[1]解放军324医院心内科,重庆400020 [2]第三军医大学大坪医院心内科

出　　处：《西南国防医药》2011年第3期242-245,共4页Medical Journal of National Defending Forces in Southwest China

摘　　要：目的研究大鼠缺血性心肌损伤后早期抑制核因子κB(NF-κB)对心功能的影响,并探讨其作用机制。方法应用大剂量异丙肾上腺素(ISO)建立大鼠缺血性心肌损伤模型,造模后24 h存活的大鼠随机分为实验组和治疗组,并设立对照组。治疗组给予腹腔注射吡咯烷二硫代氨基甲酸盐(PDTC)100 mg/kg体重,1次/d,连续26 d。检查心肌病理形态学、心肌NF-κB激活情况、心肌毛细血管密度、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、28 d进行超声心动图检查,观察心脏结构及心功能变化情况。结果实验组与治疗组心肌坏死面积无明显差异;PDTC抑制缺血性心肌损伤后心肌NF-κB的激活,下调心肌MCP-1 mRNA的表达及血清MCP-1水平,并导致肉芽组织替代受损心肌组织延迟,心肌坏死边缘区毛细血管密度减低。实验第28 d,治疗组心功能降低较实验组更为明显。结论大鼠缺血性心肌损伤后早期抑制NF-κB,可能对心功能造成不良影响,其机制可能与抑制NF-κB的激活,进而下调MCP-1的表达、影响心肌修复有关。Objective To study the effects of inhibition of nuclear factor-κB（NF-κB）early after myocardial ischemia on heart function in rats and its potential mechanisms.Methods The models of myocardial ischemic injury were established by the hypodermic injection of 170 mg/kg of isoprenaline（ISO）in rats.24 h later,the survival rats were randomly divided into experimental group and treated group（n=15）in which animals were separately injected 0.6 ml of normal saline and pyrrolidine dithiocarbamate（PDTC）at 100 mg/kg into abdominal cavity once a day for 26 d.Another 15 rats receiving the hypodermic injection of same volume of normal saline instead of ISO were served as control group.Myocardial pathomorphologic changes,NF-κB activation,myocardial capillary density,monocyte chemoattractant protein-1（MCP-1）mRNA expression and serum MCP-1 level were examined in each group.Additionally,cardiac structure and function were observed or assessed by echocardiography on day 14 and 28 of experiment.Results Cardiac necrotic area had no significant difference between experimental group and treated group.PDTC could inhibit the activation of myocardial NF-κB following myocardial ischemia,down-regulated significantly myocardial MCP-1 mRNA expression,decreased serum MCP-1 level,delayed the replacement of the damaged myocardium with granulation tissue,and lowered capillary density in the marginal zone of necrosis.On day 28,the left ventricular functions in treated group were worse than that in experimental group.Conclusion The inhibition of NF-κB early after myocardial ischemic injury in rats may aggravate heart failure,which is probably associated with the inhibited activation of myocardial NF-κB resulting in decreased myocardial MCP-1 mRNA expression and delayed myocardial repair.

关 键 词：吡咯烷二硫代氨基甲酸盐 核因子ΚB 异丙肾上腺素 心肌缺血性损伤 单核细胞趋化蛋白-1 

分 类 号：R541.4[医药卫生—心血管疾病]