溶血磷脂酸受体与大鼠急性心肌梗死后早期心肌细胞凋亡的关系  

Association of lysophosphatidic acid receptor with early myocardial apoptosis in rats after acute myocardial infarction

作　　者：陈静海[1] 陈跃峰[2] 韩变梅[1] 朱伟铨[1] 蔡艳[1] 杨跃进[2] 陈曦[1] 

机构地区：[1]中国医学科学院,中国协和医科大学,心血管病研究所,阜外心血管病医院生化研究室,北京市100037 [2]中国医学科学院,中国协和医科大学,心血管病研究所,阜外心血管病医院冠心病诊疗中心,北京市100037

出　　处：《中国临床康复》2005年第31期58-60,共3页Chinese Journal of Clinical Rehabilitation

基　　金：国家自然科学基金资助项目(30170374)~~

摘　　要：目的:本研究以急性心肌梗死为心肌损伤的诱发因素,检测急性心肌梗死后早期(48h)大鼠溶血磷脂酸3种不同受体亚型表达谱,分析其与心脏细胞的病理学特征及心功能的关系。方法:①冠状动脉结扎术后24h存活的16只雌性SD大鼠作为心肌梗死组,另设假手术组为对照组。②术后48h行血流动力学测定、称重及病理切片分析心肌肥厚状况;原位末端标记法和DNA凝胶电泳检测心肌细胞凋亡。③反转录聚合酶链反应方法检测溶血磷脂酸3种受体亚型基因表达谱。结果:①与假手术组相比,心肌梗死组左心室收缩压和左心室内压最大上升下降速率均显著降低(P<0.05～0.01),左心室舒张末压显著升高(P<0.05)。②病理切片分析心肌梗死后48h,无明显的左室扩张与心肌肥大。③DNA凝胶电泳与原位末端标记法的结果显示大鼠急性心肌梗死后心肌细胞凋亡指数显著升高犤梗死区与梗死边缘区凋亡指数分别为(21.286±15.575)%,(19.816±12.000)%,假手术组(1.270±1.070)%,P<0.01犦。④反转录聚合酶链反应结果显示,与假手术组相比,心肌梗死后早期重塑过程中溶血磷脂酸1、溶血磷脂酸2受体基因表达无显著差异,而溶血磷脂酸3受体表达增加40%(P<0.01)。结论:大鼠急性心肌梗死后早期出现左心室功能异常,早期重塑过程中(术后48h)有大量心肌细胞凋亡,但无明显的左室扩张与心室壁肥厚,而同时溶血磷脂酸3受体表达显著增加,提示溶血磷脂酸3与心肌梗死后心肌细胞凋亡相关,可能主要介导溶血磷脂酸在心肌梗死后早期的凋亡通路的调节。AIM： To investigate lysophosphatidic acid （LPA） receptor mediated signal transduction in left ventricular remodeling process, the relationship between the mRNA expression of LPA receptor subtypes and the myocardial hypertrophy and apoptosis in rat hearts after acute myocardial infarction （AMI） was studied. METHODS： ①AMI models were established with the ligation of anterior descending coronary artery in SD rats. Twenty-four hours after AMI, the 16 survivors were served as AM1 （MI） group, sham-operated group was randomly selected as controls. ② After the completion of bemodynamic study, pathological examination performed. Myocardial apoptosis was detected with in situ end labeling and DNA ladder. ③ The mRNA expression of LPA receptor subtypes was determined by RT-PCR. RESULTS：①Compared with the sham-operated group, left ventricular systolic pressure, and the maximal rates of rise and decline of ventricular pressure were significantly decreased （P 〈 0.05-0.01）, and left ventricular end diastolic pressure was notably elevated （P 〈 0.05） in the MI group. ②There was no difference in the thickness of ventricular septum and left ventricular relative mass between MI group and sham-operated group. ③ Numerous positive cells and internucleosomal degradation of DNA were found in myocardium 48 hours after AMI [infracted and border region： （21.286±15.575）%, （19.816±12.000）% respectively, sham-operated group： （1.270±1.070）%, P 〈 0.01]. ④Compared with the sham-operated group, there were no remarkably differences in mRNA expressions of LPA type 1 and type 2 receptors （LPA1 and LPA2）, whereas mRNA level of LPA3 was increased by 40% in the MI group. CONCLUSION： The left ventricular function was deteriorated after the onset of AMI. A remarkable myocardial apoptosis was accompanied with a notable increase of LPA3 mRNA expression 48 hours after AMI, suggesting that LPA3 may be concerned with the signal pathway of apoptosis in early period after AMI.

关 键 词：细胞凋亡 磷脂酸类 受体 细胞表面 心肌梗塞 

分 类 号：R542.2[医药卫生—心血管疾病]