【摘要】 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。更多还原

【Abstract】 Objective To investigate the effects of pyrrolidine dithiocarbamate(PDTC)on expression of NF-κB,MMP-2and 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.12adult Sprague-Dawley rats survived 24for 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(80mg·kg-1·d-1)for 28d,the MI group and SH group were given normal saline as control.On 28d,the cardiac function of left ventricle was measured by echocardiography.The infarct size was evaluated.The total collgen,typeⅠcollgen,typeⅢcollgen,andⅠ/Ⅲ collgen ratio were quantified histomorphometry.The mRNA and protein levels of NF-kappaBp65and MMP-2were determined by reverse transcription-polymerase chain reaction(RT-PCR)and by Western blot,respectively.Results Compared with the SH group,the values of the total collgen,typeⅠcollgen,typeⅢcollgen,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,typeⅠcollgen,typeⅢcollgen,andⅠ/Ⅲcollgen 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-kappaBp65and MMP-2in 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-2in rats.更多还原