表皮生长因子受体在肾血管性高血压大鼠心血管重构中的作用  

Epidermal growth factor receptor involvement in cardiovascular remodeling in renovascular hypertensive rats

作　　者：冯梅[1,2] 滕文浩[2] 姜雯雯[2] 向继洲[2,3] 刘慧[2,3] 杨磊[4] 

机构地区：[1]广州医科大学药学院,广东广州511436 [2]华中科技大学同济医学院基础医学院药理学系,湖北武汉430030 [3]药物靶点研究与药效学评价湖北省重点实验室,湖北武汉430030 [4]华中科技大学同济医学院附属协和医院麻醉科,湖北武汉430022

出　　处：《中国药理学通报》2016年第5期625-631,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81370299);中央高校基础研究基金(No 2012QN135);广州医科大学博士启动基金(No 2012C04)

摘　　要：目的表皮生长因子受体(EGFR)是一种受体型酪氨酸激酶,参与调节多种重要的细胞功能。既往研究表明,EGFR在促进心肌肥大和血管平滑肌细胞增殖中发挥了重要作用。本实验拟观察EGFR是否参与了肾血管性高血压心血管重构。方法本实验采用经典的"两肾一夹"(2K1C)Goldblatt肾性高血压大鼠模型,观察血压、左室心指数和心血管系统组织病理学变化,采用免疫组织化学和Western blot检测心肌和主动脉EGFR以及磷酸化ERK的表达。结果术后2周,2K1C大鼠收缩压急剧升高;6周后,左室心指数增加,心肌间质胶原纤维增生,胸主动脉内中膜增厚,表明肾血管性高血压诱导了心血管重构。与假手术组相比,2K1C大鼠心肌和主动脉EGFR表达增加,且与收缩压升高的程度相关(P<0.05)。磷酸化ERK 1/2的水平也明显上调。结论 EGFR及下游激酶ERK 1/2参与了肾血管性高血压大鼠心血管重构,并与高血压的严重程度相关。Aim To determine the possibilities and mechanisms of EGFR, a receptor protein tyrosine kinase&nbsp;associated with many important cellular processes re-sponsible for cardiovascular remodeling in renovascular hypertensive rats. Methods 2K1C hypertensive rats were used in the present study. Blood pressure was measured with the tail-cuff method. LVMI and his-topathological changes in the cardiovascular system were analysed. EGFR expressions of aorta and myocar-dium as well as phosphorylation levels of ERK in hy-pertensive rats were detected by immunohistochemistry and Western blot analysis, respectively. Results Sys-tolic blood pressure was markedly increased 2 weeks after 2K1C surgery. Cardiovascular remodeling induced by hypertension was confirmed by elevated LVMI, pro-liferation of collagen fibers in myocardial interstitium, histopathological changes in cardiovascular system and increased IMT of thoracic aorta 6 weeks after 2 K1 C&nbsp;surgery. Compared with sham rats, EGFR expression in the ventricular myocardium of 2 K1 C rats was signifi-cantly increased at 6 weeks ( P<0. 05 ) , and the EG-FR/GAPDH ratio was higher in 2 K1 C rats with higher systolic blood pressure ( P < 0. 05 ) . Phosphorylation level of ERK 1/2 was upregulated correspondingly in 2 K1 C rats ( P <0. 01 ) . Increased EGFR expression was also found in aortas of 2K1C rats, particularly in tunica intima and media. Conclusion EGFR and its down-stream kinases ERK 1/2 are involved in cardio-vascular remodeling in association with the severity of hypertension in renovascular hypertensive rats.

关 键 词：两肾一夹(2K1C) 肾血管性高血压 心血管重构 表皮生长因子受体 MAPK 大鼠 

分 类 号：R-332[医药卫生] R331.31