摘要
目的和方法 :比较自发性高血压大鼠 (SHR)和对照 (WKY)大鼠心脏和主动脉丝裂素活化蛋白激酶磷酸酶 1(MKP 1)及细胞外信号调节激酶 (ERK 1)的表达 ,并观察用磷酸钙共沉淀方法转染MKP 1基因对血管紧张素Ⅱ (AngⅡ )刺激平滑肌细胞 (VSMC) 3 H 胸腺嘧啶 (3 H TdR)掺入的影响 ,以探讨MKP 1在细胞增殖中的调节作用。结果 :①与WKY大鼠相比 ,SHR心脏和主动脉MKP 1呈低表达 ,分别降低 5 3%和 45 % (P均 <0 .0 1) ;而SHR心脏和主动脉ERK 1呈明显高表达 (P均 <0 .0 1) ,SHR心脏和主动脉ERK 1与MKP 1蛋白比值明显高于WKY。②AngⅡ 10 - 7mol L刺激VSMC增殖较对照组增加 2 5 7% (P <0 .0 1) ,转染野生型MKP 1基因细胞可使AngⅡ刺激的3 H TdR掺入较未转染的细胞降低 6 3% (P <0 .0 5 ) ,转染突变型MKP 1基因和转染空载体的VSMC对AngⅡ的刺激与单纯AngⅡ组相比无明显抑制作用 (P >0 .0 5 )。结论 :SHR心血管组织中促增殖肥大的ERK 1表达较其失活的MKP 1占优势 ,并且MKP
Aim and Methods: To investigate the role of mitogen-activated protein kinase phosphatase-1 (MKP-1) in the regulation of cells proliferation,the expression of MKP-1 and extracellular signal-regulated kinase-1 (ERK-1) in heart and aorta of spontaneous hypertensive rat (SHR) and WKY were studied. We also investigated the effect of MKP-1 genes,which were transfected into vascular smooth muscle cells (VSMC) using the classical calcium phosphate coprecipitation technique,on the incorporation of 3H-TdR in VSMC stimulated by angiotensin Ⅱ (AngⅡ). Results: ① Compared with that of WKY, MKP-1 expression in heart and aorta were significantly decreased by 53% (P<0.01) and 45% (P<0.01) in SHR ,respectively. While the expression of ERK-1 in heart and aorta of SHR were higher than that of WKY (P<0.01). The ratio of ERK-1/ MKP-1 in heart and aorta of SHR were significantly higher than that of WKY. ② 3H-TdR incorporation in VSMC stimulated by Ang Ⅱ (10 -7mol/L) was increased by 207% (P< 0.01),compared with control group. In the transfected cells with wild MKP-1 gene,AngⅡ-induced incorporation of 3H-TdR lowered 63%,compared with untransfected cells (P<0.05). There were no marked inhibitive role between mutant MKP-1-transfected cells and blank vector-transfected cells in response to AngⅡ,compared with AngⅡ group (P>0.05). Conclusion: These results showed that the expression of ERK-1 in heart and aorta isolated from SHR,which stimulated proliferation and hypertrophy of cells,is higher than that of MKP-1 which dephosphorylates and inactivated ERK-1. In addition,MKP-1 significantly inhibits AngⅡ-stimulated proliferation of VSMC.
出处
《中国应用生理学杂志》
CAS
CSCD
北大核心
2002年第1期55-58,共4页
Chinese Journal of Applied Physiology
基金
国家自然科学基金资助项目 ( 39730 2 2 0和 39970 2 95 )
