机构地区:[1]新疆医科大学第一附属医院冠心病科,新疆维吾尔自治区乌鲁木齐市830054 [2]新疆医科大学第一附属医院冠心病研究室,新疆维吾尔自治区乌鲁木齐市830054 [3]新疆医科大学第一附属医院心脏超声科,新疆维吾尔自治区乌鲁木齐市830054
出 处:《中国循环杂志》2011年第5期378-381,共4页Chinese Circulation Journal
基 金:新疆维吾尔自治区国家自然科学基金(30960133);新疆心血管病研究实验室开放课题(XJDX0903-2010-03)
摘 要: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-αmRNA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-αmRNA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。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 5 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-κB 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.
关 键 词:心肌梗塞 心室重构 心脏破裂 核因子-ΚB信号通路
分 类 号:R541[医药卫生—心血管疾病]
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