核因子-κB抑制剂对老龄小鼠急性心肌梗死后心脏破裂和心室重构的影响及机制研究

摘要

Objective: To study the effect of nuclear factor-κB ( NF-κB ) inhibitor pyrrolidine dithiocarbamate ( PDTC )on cardiac rupture and ventricular remodeling after acute myocardial infarction ( AMI) with the underlying mechanisms in old mice.Methods: A total of 212 mice with the age of 18 months were used, AMI model was created by left coronary artery ligation and the mice were divided into two groups, n= 106 in each group. AMI+PDTC group, the mice were intraperitoneally injected with PDTC 120 mg/( kg · d ) and AMI group,the mice were intraperitoneally injected with the same volume of normal saline. The cardiac rupture rate within 7 days was examined by echocardiography,the mRNA expression of TNF-α was detected by RT-PCR,the protein expression of matrix metalloproteinase-9 ( MMP-9 ) was examined by zymography and the collagen content was measured by Sirius red staining at 3,7,and 14 days after AMI respectively.Results:The cardiac rupture rate in AMI group and in AMI+PDTC group were 35. 3% vs. 15. 6% , P = 0. 000. Compared with AMI group, the left ventricular end diastolic diameter was decreased, the left ventricular weight was increased in AMI + PDTC group, P＜0. 05 respectively. Compared with AMI group,in AMI+PDTC group,the protein expression of MMP-9 was decreased 3 and 7 days after AMI,P=0. 000 respectively;the mRNA expression of TNF-α was decreased 7 days and 14 days after AMI,P = 0. 000 respectively. Compared with AMI group, the collagen content decreased in AMI+PDTC group 3 days and 7 days after AMI, P＜0. 01 respectively.Conclusion: Nuclear factor NF-kB inhibitor PDTC may decrease the cardiac rupture rate and improve the ventricular remodeling after AMI in old mice, which might be via inhibiting MMP-9 and TNF-α expression.%目的:探讨核因子(NF)-κB抑制剂二硫代氨基甲酸吡咯烷(PDTC)对老龄小鼠急性心肌梗死(AMI)后心脏破裂、心室重构的影响及机制研究.方法:18个月龄雄性C57/BL小鼠212只结扎左冠状动脉建立AMI模型,分为两组(每组106只):AMI+PDTC组术后每日腹腔注射PDTC 120 mg/(kg·d),AMI组每日注射同等剂量生理盐水.观察1周内心脏破裂率及心脏超声改变.再将AMI后3天、7天、14天不同时间行p65、肿瘤坏死因子-α mRNA表达,基质金属蛋白酶-9、2活性及心肌间质胶原含量测定.结果:与AMI组相比,AMI+PDTC组心脏破裂率降低(35.3%比15.6%),差异有统计学意义(P<0.05).与AMI组相比AMI+PDTC组舒张末期内径、左心室舒张末期外径降低,舒张期前壁厚度、收缩期前壁厚度、左心室重量增加,左心室短轴缩短率升高,差异均有统计学意义(P均<0.05),AMI后3天及7天AMI+PDTC组基质金属蛋白酶-9表达较AMI组同时间点降低(P均=0.000),AMI后3天及14天时AMI+PDTC组基质金属蛋白酶-2表达较AMI组同时间点降低(P均=0.000).AMI后7天和14天肿瘤坏死因子-α mRNA表达在AMI+PDTC组较AMI组同时间点降低(P=0.000),差异均有统计学意义.AMI后3天和7天AMI+PDTC组较AMI组心肌间质胶原容积分数降低(P值均为0.000),差异有统计学意义.结论:NF-κB抑制剂PDTC可降低老龄小鼠AMI后心脏破裂率,改善心室重构,可能是通过抑制肿瘤坏死因子-α及基质金属蛋白酶-9表达,降低胶原降解并抑制胶原合成的结果.