摘要
目的:探讨线粒体内膜能量相关转运子腺嘌呤核苷酸转运体(ANT1、ANT2)和解耦联蛋白2(UCP2)在压力负荷致心肌重塑中的机制。方法:采用腹主动脉缩窄法形成压力负荷模型。心肌ANT1、ANT2,UCP2 mRNA含量的检测采用RT-PCR凝胶成像分析法,心肌细胞凋亡的检测采用TUNEL法。利用心肌胶原形态定量分析观察心肌纤维化的改变。观察时间为30天,共9个时间点,分别为术后4 h、14 h、1、2、4、7、14、21和30天。结果:①手术组大鼠平均腹主动脉压、心重指数均证实压力负荷模型造模成功;②造模手术后14 h,手术组和假手术组均可见UCP2 mRNA表达明显增加,最大峰值较正常可达3倍左右;手术后24h UCP2 mRNA表达明显回落,回落趋势手术组和假手术组无差异;术后4天假手术组UCP2 mRNA表达回落至正常水平,而手术组仍处于较高水平状态,平均达假手术组的1.5倍左右;③缩窄后约4天ANT1 mRNA的含量上调,而ANT2 mRNA的含量下调,并于第7天分别达到峰值和谷值。术后14天手术组大鼠心肌ANT1 mRNA和ANT2 mRNA的含量均接近假手术组水平,并持续至实验结束;④心肌细胞凋亡指数(CAI)在术后4 h即有升高,在4天时进入高峰期并持续至第7天,其后低水平持续存在,直至实验结束。假手术组未发现凋亡的存在;⑤与假手术组相比,手术组心肌血管周围胶原面积分数(PVCF)在术后14 h开始升高,2天达高峰,其后处于平台期;而心肌胶原容积分数(CVF)在手术14天后才明显增加,并持续增高。结论:①心肌血管周围纤维化早于凋亡和心肌间质性纤维化。凋亡是心肌实质性纤维化的关键环节;②心肌UCP对外界疼痛、寒冷等刺激存在短暂应激性反应,而心肌ANT无反应或反应甚微;③心肌UCP、ANT的表达变化提示两者参与了压力负荷致心肌重塑的初始化阶段,两者所决定的能量和凋亡的平衡可能也制约了心肌重塑的步伐。
Objective: To illustrate the mechanism of myocardial remodeling, we studied the expression of energy-related translocators ( ANT1, ANT2 and UCP2) mRNA within mitochondrial inner membrane under pressure load in rats. Methods: Abdominal aorta coarctation was used to establish the pressure load model in rats. The relative content of ANT1, ANT2 and UCP2 mRNA in myocardium was detected by RT-PCR and gel electrophoresis Imaging. The TUNEL method was applied to detect the myocardial apoptosis. The cardiac collagen morphological quantitative analyses discovered the changes of the myocardial fibrosis. The observed cycle is 30 days, and there are 9 time points, 1 h, 14 h, 1 d,2d,4d,7d, 14 d, 21 d and 30 d after operation, respectively. Results:①The results of the mean abdominal aorta pressure and the cardiac weight index confirmed the utility of the animal model. ② At the 14h after operation , there was an evident increase of the expression of UCP2 mRNA both in operated group and in sham-operated group. The expression of UCP2 mRNA increased about 3-fold as normal. Within 24 h after operation , the expression of the UCP2 mRNA was obviously recovered. About recovery there was no difference between operated group and sham-operated group. Four days after operation, the expression of UCP2 mRNA in sham-operated group recovered to normal. But there was a continuous high level of UCP2 mRNA in operated group. In average, it increased 1. 5-fold as sham-operated group. ③At about 4 days after coarctation, the expression of ANT1 mRNA was upregulated, but the expression of ANT2 mRNA was downregulated, and both reach peak and valley respectively at 7 days. The expression of ANT1 mRNA and ANT2 mRNA in operated group are close to that of the sham-opreated group at 14 days after operation.④The cardiac apoptosis index (CAI) increased significantly at 4 hours after operation, reached a plateau at 4 day and maintained at high levels up to the 7th day. Afterwards, the CAI exists at low levels continuously to the end of the experiment. H
出处
《医学研究生学报》
CAS
2005年第B05期24-28,33,共6页
Journal of Medical Postgraduates
关键词
腺嘌呤核苷酸转运体
解耦连蛋白
线粒体
心肌重塑
压力负荷
大鼠
Adenine nucleotide translocator
Uncoupling protein
Mitochondrion
Myocardial remodeling
Pressure load
Rat
