MCP-1 McAb和Losartan拮抗VSMCs的增殖与迁移效应的实验研究

Antagonistic effect of MCP-1 McAb and Losartan on proliferation and migration of Ang-Ⅱ-mediated VSMCs in vitro

目的 探讨单核细胞趋化蛋白 1单克隆抗体 (MCP 1McAb)或Losartan拮抗血管紧张素Ⅱ (AngⅡ )介导的血管平滑肌细胞 (VSMCs)增殖与迁移效应的可能性 ,为防治动脉硬化 (AS)提供一定的理论依据。方法 采用改良的Boyden小室法检测VSMCs的迁移效应 ;以MTT法、3H TdR掺入法、3H 脯氨酸标记法和VSMCs计数评价VSMCs的增殖效应 ;将培养的VSMCs分为 5组 :2 %胎牛血清 ( 2 %FCS)组、AngⅡ组 (其浓度为10 - 1 0 ～ 10 - 6 mol L)、Losartan组 (其浓度为 10 - 7～ 10 - 5 mol L)、MCP 1McAb组 (终浓度为 10 μg ml)和阳性对照组 (含 5 %的酵母多糖活化血清 )。结果 ①AngⅡ具有剂量依赖性的促进VSMCs增殖与迁移效应 ;②MCP 1McAb或Losartan能有效地拮抗AngⅡ介导的VSMCs增殖与迁移效应。结论 MCP 1McAb或Losartan对动脉硬化性疾病可能具有较大的应用前景。

Objective To study the possibility of monocyte chemotactic protein 1 monoclonal antibody(MCP 1 McAb) or Losartan antagonizing the proliferation and migration of cultured vascular smooth muscle cells (VSMCs) mediated by angiotensin Ⅱ(AngⅡ). Methods The cultured VSMCs were divided into 5 groups, i.e. 2% fetal calf serum group (2%FCS group), AngⅡ group (concentration of 10 -10 -10 -6 mol/L), Losartan group (concentration of 10 -7 -10 -5 mol/L), MCP 1 McAb group(final concentration of 10 μg/ml) and positive control (concentration 5% zymosan). The migration effects of cultured VSMCs were examined by a modified Boyden's chamber. And the proliferation effect was evaluated with MTT, thiazolyl blue intaking, 3H TdR and 3H proline incorporation as well as VSMCs count. Results ①AngⅡexerted an enhancing effect on the proliferation and migration of cultured VSMCs in a concentration dependent manner; ②Both MCP 1 McAb and Losartan could antagonize the proliferation and migration of AngⅡ mediated VSMCs. Conclusion It is suggested that MCP 1 McAb and Losartan both play predominant roles in inhibiting the proliferation and migration of VSMCs and are prospective in the treatment of atherosclerotic diseases.