溶血磷脂酸及其受体在大鼠心肌重塑中的作用

目的研究溶血磷脂酸（LPA）及其受体对心脏成纤维细胞增殖的影响及与心肌重塑的关系，探索LPA在心脏组织的生物学作用。方法采用^3H-TdR或^3H-Leu掺入法测定LPA对心脏成纤维细胞DNA及蛋白质合成的影响；用Northern杂交检测c-FOS mRNA的表达；RT-PCR测定大鼠急性心梗心肌组织LPA受体基因表达。结果LPA以浓度依赖方式刺激乳鼠心脏成纤维细胞DNA合成和蛋白质合成；LPA刺激成纤维细胞c-FOS mRNA表达呈时间与剂量依赖性；G-蛋白偶联受体阻断剂苏拉明（suramin）能有效抑制LPA诱导的成纤维细胞DNA合成及c-FOSmRNA表达上调。大鼠急性心梗5周后，心肌梗死区LPA受体mRNA表达上调。结论LPA通过G-蛋白偶联受体诱导c-FOS基因表达增加，从而刺激心脏成纤维细胞增殖，参与急性心梗后心肌重塑的形成和发展。LPA在心脏组织中有重要的生物学功能。

Roles of lysophophatide acid and its receptor in heart remodeling of rat

Objective To investigate the effects of LPA and LPA receptor on proliferation of cardiac fibroblasts and heart remodeling, to explore the biological function of LPA in heart tissue. Methods DNA and protein synthesis of cardiac fibroblasts were detected by 3 H-TdR and 3 H-Leu incorporation respectively. The c-FOS mRNA expression was determined by Northern blot. The expression of LPA receptor gene was determined by RT-PCR. Results LPA induced the increase of DNA synthesis and protein synthesis of rat myocardial fibroblasts in a concentration dependent manner. LPA stimulated the expression of c-FOS mRNA of myocardial fibroblasts in a time-and dose-dependent manner. Suramin, an inhibitor of G-protein coupled receptor, significantly inhibited LPA-induced DNA synthesis of myocardial fibroblasts and the expression of c- FOS mRNA. The LPA receptor mRNA was increased in myocardial infarction region after 5 weeks of acute myocardial infarction attack. Conclusions These results indicated that LPA has an important biological role in heart tissue through stimulating the increase of c-FOS mRNA level in the G-protein cascade and the proliferation of cardiac fibroblasts, and participates in the form and progress of heart remodeling.