丝裂素活化蛋白激酶磷酸酶-1抑制血管紧张素Ⅱ刺激的血管成纤维细胞活化  

Mitogen-activated protein kinase phosphatase-1 inhibits the activation of vascular fibroblasts stimulated by angiotensin Ⅱ

作　　者：柴三葆[1] 佟利家[1] 卜定方[2] 庞永正[2] 唐朝枢[1] 李菊香[3] 

机构地区：[1]北京大学第一医院心血管病研究所,北京100034 [2]北京大学第一医院中心实验室,北京100034 [3]北京大学基础医学院生理学和病理生理学系

出　　处：《北京大学学报（医学版）》2002年第1期24-27,共4页Journal of Peking University:Health Sciences

基　　金：国家自然科学基金 ( 39730 2 2 0和 39970 2 95)资助~~

摘　　要：目的 :观察丝裂素活化蛋白激酶磷酸酶 1 (mitogen activatedproteinkinasephosphatase 1 ,MKP 1 )对血管紧张素Ⅱ (AngⅡ )刺激的血管成纤维细胞增殖及胶原合成和分泌的影响。方法 :用磷酸钙共沉淀的方法向血管成纤维细胞转染MKP 1的基因 ;测定培养的血管成纤维细胞内丝裂素活化蛋白激酶 (mitogen activatedproteinkinase ,MAPK)活性、3H 胸腺嘧啶 (3H TdR)及3H 脯氨酸参入。结果 :1 0 7mol·L 1 AngⅡ刺激培养的血管成纤维细胞后其MAPK活性及3H TdR参入较对照组增加 2 93 % (P <0 .0 1 )及 1 90 % (P <0 .0 1 ) ;胶原的合成和分泌较对照组分别增加 1 4 6 % (P <0 .0 1 )和 50 2 % (P <0 .0 1 )。而转染了MKP 1野生型基因的细胞与未转染时相比 ,AngⅡ诱导的MAPK活性和3H TdR参入分别低 65 % (P <0 .0 1 )和 67% (P <0 .0 1 ) ;参入细胞内及介质中的3H 脯氨酸分别低65 % (P <0 .0 5)和 80 % (P <0 .0 1 )。转染MKP 1突变型及MKP 1空载体基因的细胞对于AngⅡ的上述各种刺激作用均无明显抑制。结论 :MKP 1具有抑制AngⅡ刺激的血管成纤维细胞MAPK激活、成纤维细胞增殖及胶原合成和分泌的作用 ,提示MKPObjective: To observe the effect of mitogen activated protein kinase phosphatase 1 (MKP 1) on angiotensin Ⅱ (Ang Ⅱ) stimulated mitogen activated protein kinase (MAPK) activity, cell proliferation and collagen synthesis and secretion in cultured vascular fibroblasts. Methods: MKP 1 gene was transfected into vascular fibroblasts by the classical calcium phosphate coprecipitation technique. MAPK activity, 3 H Thymidine ( 3H TdR) and 3 H Proline incorporation were measured in cultured vascular fibroblasts treated with AngⅡ. Results: AngⅡ (10 7 mol·L 1 ) strongly increased MAPK activity and 3H TdR incorporation about 293%( P <0.01) and 190%( P <0.01), together with the marked increases of 146% P <0.01) and 502% P <0.01) in collagen synthesis and secretion of cultured vascular fibroblasts, compared with that in the control group. In the transfected cells with wild MKP 1 gene, AngⅡ stimulated MAPK activity and 3 H TdR were downregulated by 65%( P <0.01) and 67%( P <0.01). 3 H Proline incorporations were significantly decreased by 65% ( P <0.05) in cells and 80%( P <0.01) in medium respectively, compared with that of untransfected cells. Both cells transfected with mutant MKP 1 and bland vector didn't inhibit the effect of AngⅡ significantly. Conclusion: These results showed that MKP 1 inhibited AngⅡ stimulated vascular fibroblasts MAPK activity, vascular fibroblasts proliferation, as well as collagen synthesis and secretion, suggesting MKP 1 might participate in the regulation of vascular remodeling stimulated by AngⅡ.

关 键 词：丝裂素活化蛋白磷酸酶 成纤维细胞 药物作用 胶原 代谢 血管紧张素Ⅱ 动脉粥样硬化 高血压 

分 类 号：R543[医药卫生—心血管疾病]