CAJ | 학술논문

为了探索血小板源生长因子(platelet-derived growth factor,PDGF)受体介导的信号转导在自发性高血压大鼠(spontaneously hypertensive rats,SHR)心肌肥大中的作用,实验采用Western blot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(extracellular signal-regulated kinase 1/2,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ERK 1/2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<0.05),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=0.01),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[3H]亮氨酸掺入量明显增加,ERK 1/2 的磷酸化水平明显升高。上述结果提示:血小板源生长因子受体在自发性高血压大鼠心肌肥大中可能起着重要作用。
위료탐색혈소판원생장인자(platelet-derived growth factor,PDGF)수체개도적신호전도재자발성고혈압대서(spontaneously hypertensive rats,SHR)심기비대중적작용,실험채용Western blot법검측SHR급기대조WKY대서심기PDGF수체β화세포외신호조절격매(extracellular signal-regulated kinase 1/2,ERK 1/2)적단백표체화ERK 1/2린산화수평적변화。결과현시:4주령SHR적수축압、서장압、±dp/ dtmax화심기비대지수여동령WKY대서상비균무명현차이,이12주령SHR상술지표여동령WKY대서상비균명현승고,표명12주SHR이발생고혈압,심장수축공능대상성증강,병출현심기비대。4주령SHR심기PDGF수체β화ERK 1/2적린산화수평이급 ERK 1/2 적단백표체수평여동령대조상비균무명현변화,12 주시 SHR 심기 PDGF 수체β적단백표체교동령 WKY 증가32.77% (P<0.05),PDGF 수체개도적신호전도통로적하유신호분자 ERK 1/2 적린산화수평교동령 WKY 승고 19.6% (P=0.01),표명ERK 1/2적활화증가,단ERK 1/2적단백표체수평상무변화。위진일보명학PDGF수체β재심기세포생장중적작용급기여ERK 1/2활성적관계,채용PDGF-BB자격배양적유서심기세포,발현[3H]량안산참입량명현증가,ERK 1/2 적린산화수평명현승고。상술결과제시:혈소판원생장인자수체재자발성고혈압대서심기비대중가능기착중요작용。
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/ dtmax 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,[3H]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 [3H]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.