PDTC对大鼠心肌梗死后NF-κB与MMP-2表达及心肌胶原重塑的影响

Effects of pyrrolidine dithiocarbamate on expression of NF-κB,MMP-2 and collagen remodeling after myocardial infarction in rats

目的探讨二硫代氨基甲酸吡咯烷(PDTC)对大鼠心肌梗死后核转录因子κB(NF-κB)、基质金属蛋白酶-2(MMP-2)的表达及胶原重塑的影响。方法制作大鼠心肌梗死模型,分为PDTC干预(PD)组和心肌梗死对照(MI)组,另设假手术(SH)组,每组大鼠6只。PD组于术后24h腹腔注射PDTC 80mg·kg-1·d-1,连续给药28d后行超声心动图检查评定心功能,处死动物,计算总胶原、Ⅰ型胶原、Ⅲ型胶原含量和梗死面积,实时荧光定量逆转录聚合酶链反应和免疫印迹法分别检测NF-κBp65及MMP-2的mRNA和蛋白质表达量。结果与SH组比较,MI组和PD组的总胶原、Ⅰ型胶原、Ⅰ/Ⅲ胶原比值明显增大,NF-κBp65和MMP-2的mRNA及蛋白质表达量明显增加,差异均具有统计学意义(P<0.01)。与MI组比较,PD组总胶原、Ⅰ型胶原、Ⅰ/Ⅲ胶原比值改变明显减轻,NF-κBp65和MMP-2的mRNA及蛋白质表达量明显降低,差异有统计学意义(P<0.01)。结论 PDTC在一定程度上能改善大鼠心肌梗死后心肌胶原重塑,其机制可能与抑制NF-κB激活,下调基质金属蛋白酶(如MMP-2)表达有关。

Objective To investigate the effects of pyrrolidine dithiocarbamate（PDTC） on expression of NF-κB,MMP-2 and left ventricular collagen remodeling following acute myocardial infarction in rats. Methods The myocardial infarction model in rat was induced by ligation of left anterior descending coronary artery. 12 adult Sprague-Dawley rats survived 24 for h after acute myocardial infarction were randomly divided into the myocardial infarction（MI） group and the PDTC-treated（PD） group. Six rats were designated as sham-operated group（SH group）. The PD group was intraperitoneally injected with PDTC（80 mg· kg^-1 · d^-1 ） for 28 d, the MI group and SH group were given normal saline as control. On 28 d,the cardiac function of left ventricle was measured by echocardiography. The infarct size was evaluated. The total collgen, type I collgen, type III collgen, and I /III collgen ratio were quantified histomorphometry. The mRNA and protein levels of NF-kappaBp65 and MMP-2 were determined by reverse transcription-poty merase chain reaction（RT-PCR） and by Western blot, respectively. Results Compared with the SH group, the values of the total collgen, type I collgen, type III cotlgen, and I/III collgen ratio in the MI group and the PD group were significantly increased, the differen had statistical significance （P〈0.01）. The values of the total collgen, type I collgen, type II collgen,and I /III collgen ratio in the PD group were notably decreased than those in the MI group（P^0.01）. Moreover,the mRNA and protein levels of NF-kappaBp65 and MMP-2 in the PD group were lower than those in the MI group,the difference had statistical significance（P〈0.01）. Conclusion Left ventricular collagen remodeling following acute myocardial infarction could be improved by PDTC to some extent, which mechanism could be related with inhibiting NF-kappaB activation and down--regulating the expression of MMP 2 in rats.