普伐他汀对非对称性二甲基精氨酸促血管平滑肌细胞增殖的影响  

Effect of pravastatin on proliferation of vascular smooth muscle cells stimulated by asymmetric dimethylarginine

作　　者：郭征[1] 熊燕[1] 

机构地区：[1]中南大学药学院药理学教研室,湖南长沙410078

出　　处：《中国药理学与毒理学杂志》2004年第6期421-426,共6页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金资助项目 (30 2 715 0 7)~~

摘　　要：目的　探讨非对称性二甲基精氨酸 (ADMA)对血管平滑肌细胞增殖的作用和普伐他汀对ADMA促平滑肌细胞增殖的影响及其机制。方法　用[3H]TdR掺入法和MTT比色法检测ADMA对培养的牛胸主动脉平滑肌细胞增殖作用的量效关系和时效关系 ,以及普伐他汀等药物对ADMA刺激平滑肌细胞增殖的影响。结果　用 30～ 30 0 μmol·L- 1ADMA分别孵育平滑肌细胞后 ,都明显增加血管平滑肌细胞DNA的合成 ,表现在 [3H]TdR掺入量由对照组的(6 38± 134)cpm增加到大剂量ADMA组的 (12 79±111)cpm。用 30 0 μmol·L- 1ADMA孵育细胞 2 4～ 96h呈时间依赖性地促进血管平滑肌细胞增殖 ,表现为 [3H]TdR掺入量随着时间的延长分别增加为对照组的 1.5 ,2 .7,4 .3和 5 .6倍。普伐他汀 (10 0 μmol·L- 1)可逆转ADMA所致的细胞DNA合成的增加 ,[3H]TdR掺入量由ADMA单独孵育组的 (6 10± 2 0 2 )cpm降低至普伐他汀处理组的 (35 6± 12 6 )cpm。此外 ,一氧化氮供体硝普钠和抗氧化剂吡咯烷二硫代氨基甲酸盐处理后也可逆转这种增加。MTT法测定细胞数也证明 ,30～ 30 0 μmol·L- 1普伐他汀呈剂量依赖性地对抗ADMA所致的平滑肌细胞增殖。结论ADMA可促进血管平滑肌细胞的增殖 ;普伐他汀对ADMA所诱导的平滑肌细胞增殖具有抑制作用 ;这两者均可能与细?AIM To investigate the effect of asymmetri c dimethylarginine (ADMA) on proliferation of vascular smooth muscle cells (VSMC s) and determine whether pravastatin(PT) inhibits the proliferation of VSMCs ind uced by ADMA. METHODS VSMCs from bovine thoracic aorta were inc ubated with different concentrations of ADMA (30-300 μmol·L -1) or treat ed with ADMA (300 μmol·L -1) for varied periods (24-96 h). [ 3H]T dR incorporation and MTT were used to evaluate proliferation of VSMCs after expo sure to ADMA and the effect of PT or other drugs on the ADMA-induced VSMCs prol i feration. RESULTS ADMA (30-300 μmol·L -1) increased the DNA synthesis of VSMCs, showing that the [ 3H]TdR incorporation increased fr om (638±134)cpm (control group) to (1128±342)cpm (300 μmol·L -1 ADMA-t reated group). Additionally, incubation of VSMCs with 300 μmol·L -1 ADMA for 24-96 h significantly stimulated the DNA synthesis of VSMCs in a time-d ependent manner. The amount of [ 3H]TdR incorporation into VSMCs was incr eased to 1.5-, 2.7-, 4.3-, and 5.6-fold of control group, respectively. PT(100 μmol·L -1) reversed the increase of DNA synthesis in VSMCs induced by ADMA,as expressed by the [ 3H]TdR incorporation into VSMCs d ecrease d from (610±202)cpm of ADMA-treated group to (356±126)cpm of PT-treated group. Moreover, the increase of DNA synthesis in VSMCs induced by ADMA was also significantly suppressed by treatment with sodium nitroprusside, a donor of NO, and pyrrolidine dithiocarbamate, an antioxidant. The results of MTT assay c onfirmed that PT (30-300 μmol·L -1) reduced the ADMA-induced proliferat ion of VSMCs in a concentration-dependent manner. CONCLUSION ADMA accelerates proliferation of VSMCs and PT inhibits ADMA-induced prolif eration of VSMCs, which may relate to the alterations of nitric oxide synthesis and superoxide anion production in VSMCs.

关 键 词：二甲基非对称性精氨酸 普伐他汀 血管平滑肌 细胞增殖 

分 类 号：R96[医药卫生—药理学]