CAJ | 학술논문

背景:血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)是诱导心肌肥大的强刺激因子,血小板衍生生长因子(platelet-derived growthfactor,PDGF)也是致心肌肥大因素之一,AngⅡ是否可以通过诱导PDGF受体表达进一步促使心肌肥大?目的:探讨丝裂素活化蛋白激酶在AngⅡ致心肌细胞肥大的作用,为心肌肥大的防治提供理论依据.设计:以分离纯化培养的Wistar乳鼠心肌细胞为研究对象的对照性实验研究.单位:一所大学的病理生理教研室.材料:实验在北京大学医学院病理生理学实验室进行.实验动物为80只出生1～3 d的Wistar乳鼠(北京大学医学部动物中心提供),雌雄不限.均在细胞培养室取出心脏做心肌细胞培养.干预:分离纯化培养的乳鼠心肌细胞,分为3组,以1×10-7 mol/L AngⅡ刺激为AngⅡ组;以1×10-5 mol/L PD98059(一种丝裂素活化蛋白激酶抑制剂)预孵育30 min后再用AngⅡ刺激为PD98059组;以正常的乳鼠心肌细胞为对照组.培养24 h后采用免疫印迹法测定每组心肌细胞PDGF-β受体的含量.主要观察指标:各组心肌细胞PDGF-β受体的含量.结果:AngⅡ刺激培养24 h的乳鼠心肌细胞PDGF-β受体表达(432.41±54.08)和对照组(197.65±44.10)比较增强,差异有显著性意义(q=6.77,P<0.01),PD98059组PDGF-β受体表达(317.2±21.12)与AngⅡ组比较明显下降,差异有显著性意义(q=3.91,P<0.05),但并未完全恢复至对照组水平,两者比较差异有显著性意义(q=3.85,P<0.05).结论:AngⅡ可以上调心肌细胞PDGF-β受体的表达,丝裂素活化蛋白激酶参与这一过程.这可能是AngⅡ促进心肌肥大的又一个重要机制.此研究结果可为心脏康复的一、二级预防提供实验学数据.
배경:혈관긴장소Ⅱ(angiotensinⅡ,AngⅡ)시유도심기비대적강자격인자,혈소판연생생장인자(platelet-derived growthfactor,PDGF)야시치심기비대인소지일,AngⅡ시부가이통과유도PDGF수체표체진일보촉사심기비대?목적:탐토사렬소활화단백격매재AngⅡ치심기세포비대적작용,위심기비대적방치제공이론의거.설계:이분리순화배양적Wistar유서심기세포위연구대상적대조성실험연구.단위:일소대학적병리생리교연실.재료:실험재북경대학의학원병리생이학실험실진행.실험동물위80지출생1～3 d적Wistar유서(북경대학의학부동물중심제공),자웅불한.균재세포배양실취출심장주심기세포배양.간예:분리순화배양적유서심기세포,분위3조,이1×10-7 mol/L AngⅡ자격위AngⅡ조;이1×10-5 mol/L PD98059(일충사렬소활화단백격매억제제)예부육30 min후재용AngⅡ자격위PD98059조;이정상적유서심기세포위대조조.배양24 h후채용면역인적법측정매조심기세포PDGF-β수체적함량.주요관찰지표:각조심기세포PDGF-β수체적함량.결과:AngⅡ자격배양24 h적유서심기세포PDGF-β수체표체(432.41±54.08)화대조조(197.65±44.10)비교증강,차이유현저성의의(q=6.77,P<0.01),PD98059조PDGF-β수체표체(317.2±21.12)여AngⅡ조비교명현하강,차이유현저성의의(q=3.91,P<0.05),단병미완전회복지대조조수평,량자비교차이유현저성의의(q=3.85,P<0.05).결론:AngⅡ가이상조심기세포PDGF-β수체적표체,사렬소활화단백격매삼여저일과정.저가능시AngⅡ촉진심기비대적우일개중요궤제.차연구결과가위심장강복적일、이급예방제공실험학수거.
BACKGROUND: Angiotensin Ⅱ (Ang Ⅱ) can induce cardiac hypertrophy and platelet-derived growth factor(PDGF) also stimulates cardiac hypertrophy. Is AngⅡ responsible for the pathogenesis of cardiac hypertrophy by inducing PDGF receptor expression?OBJECTIVE: To investigate the effect of mitogen activated protein kinase (MAPK) on the role of cardiac hypertrophy induced by Ang Ⅱ in cardiac myocytes so as to provide theoretical basis for clinical prevention and cure of cardiac hypertrophy.DESIGN: Controlled experimental study taking cardiac myocytes of cultured neonatal rats as subjects.SETTING: Department of pathophysiology in a university.MATERIALS: The experiment was completed in the Department of Pathophysiology, Medical College of Peking University. A total of 80 Wistar rats of either gender, aged 1 - 3 days, were provided by the Animal Center of Medical College, Peking University. Their hearts were removed for myocyte culture in the Cell Culture Laboratory.INTERVENTIONS: The cultured neonatal rat cardiac myocytes treated with 10-7mol/L Ang Ⅱ were Ang Ⅱ group, and those preincubated with 10-5mol/L PD98059(an antagonist of MAPK) for 30 minutes and then treated with Ang Ⅱ were PD98059 group. Cardiac myocytes of normal neonatal rats were as control group. The expression of PDGF-β was detected by western blot at 24 hours.MAIN OUTCOME MEASURES: Content of PDGF-β receptor in neonatal rat cardiac myocytes.RESULTS: The expression of PDGF-β receptor induced by Ang Ⅱ at neonatal rat cardiac myocytes markedly increased at 24 hours (432.41 ± 54.08) compared with that of control group(197.65 ± 44. 10) ( q = 6.77, P< 0.01 ). PDGF-β receptor expression of PD98059 group(317.2 ± 21.12) decreased compared with that of Ang Ⅱ group(q = 3.91, P < 0.05) .However, the expression did not return to the level of control group, and there was significant difference between PD98059 group and control group( q= 3.85, P <0.05).CONCLUSION: The results indicate that angiotensin Ⅱ promotes cardiac hypertrophy through inducing expression of PDGF receptor, in which mitogen activated protein kinase participates in. Maybe it is another important mechanism for Ang Ⅱ -induced cardiac hypertrophy. The results can provide experimental data for the primary and secondary prevention in heart rehabilitation.