血小板源生长因子受体介导的信号转导在自发性高血压大鼠心肌肥大中的作用(英文)  

Role of platelet-derived growth factor receptor-mediated signal transduction in myocardial hypertrophy of spontaneously hypertensive rats

作　　者：刘洁[1] 白桦[2] 邢东琦[1] 孙银平[3] 吴立玲[1] 

机构地区：[1]北京大学医学部生理与病理生理学系,北京100083 [2]邮电总医院心内科,北京100032 [3]新乡医学院病理生理学教研室,新乡453003

出　　处：《生理学报》2002年第2期159-164,共6页Acta Physiologica Sinica

基　　金：hisstudywassupportedbytheNationalNaturalScienceFoundationofChina (No 3 0 170 3 79and 3 9870 3 5 6)

摘　　要：为了探索血小板源生长因子 (platelet derivedgrowthfactor,PDGF)受体介导的信号转导在自发性高血压大鼠(spontaneouslyhypertensiverats,SHR)心肌肥大中的作用 ,实验采用Westernblot法检测SHR及其对照WKY大鼠心肌PDGF受体β和细胞外信号调节激酶 (extracellularsignal regulatedkinase1/ 2 ,ERK 1/ 2 )的蛋白表达和ERK 1/ 2磷酸化水平的变化。结果显示 :4周龄SHR的收缩压、舒张压、±dp/dtmax和心肌肥大指数与同龄WKY大鼠相比均无明显差异 ,而 12周龄SHR上述指标与同龄WKY大鼠相比均明显升高 ,表明 12周SHR已发生高血压 ,心脏收缩功能代偿性增强 ,并出现心肌肥大。 4周龄SHR心肌PDGF受体 β和ERK1/ 2的磷酸化水平以及ERK 1/ 2的蛋白表达水平与同龄对照相比均无明显变化 ,12周时SHR心肌PDGF受体 β的蛋白表达较同龄WKY增加 32 77% (P <　　　　　　　　　 0 0 5 ) ,PDGF受体介导的信号转导通路的下游信号分子ERK 1/ 2的磷酸化水平较同龄WKY升高 19 6 % (P =0 0 1) ,表明ERK 1/ 2的活化增加 ,但ERK 1/ 2的蛋白表达水平尚无变化。为进一步明确PDGF受体 β在心肌细胞生长中的作用及其与ERK 1/ 2活性的关系 ,采用PDGF BB刺激培养的乳鼠心肌细胞 ,发现 [3 H]亮氨酸掺入量明显增加 ,ERK 1/The role of platelet derived growth factor (PDGF) receptor mediated signal transduction in myocardial hypertrophy of spontaneously hypertensive rats (SHR) was investigated. The protein expressions of PDGF β receptor and extracellular signal regulated kinase 1/2 (ERK 1/2 ) and the level of phosphorylated ERK 1/2 (pERK 1/2 ) in cardiac tissues from 4 and 12 week old SHR and their age matched normotensive control Wistar Kyoto rats (WKY) were examined by Western blot analysis. The results showed that arterial systolic and diastolic blood pressure, ± dp / dt max and the ratio of left ventricular weight to body weight were unchanged in 4 week old SHR, while they were increased significantly in 12 week old SHR as compared with those of age matched WKY. There were no differences in PDGF β receptor, pERK 1/2 , and ERK 1/2 between 4 week old WKY and SHR. The expression of PDGF β receptor of 12 week old SHR was significantly increased by 32 77% ( P <0 05) as compared with that of age matched WKY. Although the expression of ERK 1/2 , the downstream signal molecule of PDGF receptor mediated signal transduction pathway, was unchanged, the level of pERK 1/2 , the active form of ERK 1/2 , was increased by 19 6% ( P =0 01) in 12 week old SHR. To further elucidate the effect of PDGF β receptor on cardiomyocyte growth and the relation between PDGF β receptor and ERK 1/2 activity, leucine incorporation assay and immunoblotting analysis of pERK 1/2 were performed after cultured neonatal rat cardiomyocytes were stimulated with PDGF BB. It was shown that leucine incorporation and pERK 1/2 level were significantly increased after PDGF BB stimulation. These findings suggest that PDGF β receptor may play an important role in the myocardial hypertrophy of spontaneously hypertensive rats.

关 键 词：血小板源生长因子受体 介导 信号转导 自发性高血压 大鼠 心肌肥大 

分 类 号：R544.1[医药卫生—心血管疾病] R542.2[医药卫生—内科学]