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辛伐他汀对血管加压素诱导大鼠心肌成纤维细胞增殖的影响及其与小窝蛋白-1表达的关系(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2008年第2期
页码:
127-131
栏目:
基础研究
出版日期:
2008-03-20

文章信息/Info

Title:
Effect of Simvastatin on proliferation of adult rat CFs induced by AVP and its relationship with expression of caveolin-1 protein
作者:
何燕萍赵连友郑强荪刘少伟赵晓燕陆晓龙
第四军医大学唐都医院心内科,陕西 西安 710038
Author(s):
HE Yanping ZHAO Lianyou ZHENG Qiangsun LIU Shaowei ZHAO Xiaoyan LU Xiaolong
Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi, China
关键词:
小窝蛋白-1血管加压素 辛伐他汀心肌成纤维细胞增殖
Keywords:
caveolin-1 simvastatin arginine vasopressin cardiac fibroblasts proliferation
分类号:
R972.6
DOI:
-
文献标识码:
A
摘要:
目的 研究辛伐他汀(simvastatin,Sim)对精氨酸血管加压素(arginine vasopressin,AVP,简称血管加压素)诱导成年大鼠心肌成纤维细胞(CFs)增殖的影响及其与小窝蛋白1(caveolin1,cav1)的关系。方法 离体培养成年大鼠CFs,以四氮唑盐(MTT)比色法检测CFs的增殖,流式细胞分析仪测定其细胞周期,蛋白免疫印迹法检测cav1蛋白的表达。观察cav1在AVP诱导大鼠CFs增殖前后及Sim干预后的变化。结果 10-7mol/L AVP干预24 h后,MTT比色法检测CFs的吸光值(A)(0.24±0.03)较对照组(0.15±0.02)显著增高(P<0.01);给予10-8~ 10-5 mol/L的Sim和AVP共同干预后,CFs的A值呈递减趋势,分别为0.22±0.03、0.21±0.02、0.19±0.02和0.17±0.02,均较AVP组降低,差异具有统计学意义(P<0.05,P<0.01)。以10-7 mol/L 的AVP干预24 h后,CFs S期的百分率(19.52±1.07)和增殖指数(48.25±1.27)较对照组(分别为7.02±0.27和18.93±3.03)均显著增高(均P< 0.01);10-7~10-5 mol/L Sim与10-7 mol/L AVP联合干预组CFs S 期的百分率和增殖指数均较AVP单独干预组降低,差异具有统计学意义(P<0.05,P<0.01)。10-7mol/L 的AVP分别与10-8~ 10-5 mol/L的Sim共同干预后,cav1蛋白的表达呈浓度依赖性地减少。 甲羟戊酸(MVA)可逆转Sim对CFs增殖的抑制效应,并拮抗Sim诱导的cav1蛋白表达的降低。结论 Sim可抑制AVP诱导的CFs增殖,Sim的干预效应可能受到cav1蛋白表达的调节。
Abstract:
AIM To study the effect of simvastatin (Sim) on the proliferation of rat cardiac fibroblasts (CFs) induced by arginine vasopressin (AVP) and its relationship with expression of caveolin1 (cav1) protein. METHOD SCFs were isolated from adult SD rats and cultured. The cellular proliferation and cell cycle were evaluated by MTT colorimetry (A490 value) and flow cytometry (FCM), respectively. The expression of cav1 protein was analyzed by immunoblotting. RESULTS ①10-7mol/L AVP significantly increased A490 value (0.24 ±0.03) of CFs in comparison with that in control group (0.15±0.02, P<0.01). 10-8-10-5mol/L Sim plus AVP decreased the A490 value of CFs in a concentrationdependent manner (0.22±0.03, 0.21±0.02, 0.19±0.02 and 0.17±0.02, respectively, P<0.05-0.01 vs control). ② The percentage of cells in S phase and proliferation index were markedly increased by 10-7 mol/ L AVP compared with those in control (19.52±1.07 and 48.25±1.27 vs 7.02±0.27 and 18.93±3.03, both P< 0.01). In 10-7-10-5mol/L Sim plus 10-7 mol/L AVP group, the percentage of cells in S phase and the value proliferation index were significantly lower than those in AVP singledrug group (P<0.05,P<0.01). ③In the presence of 10-7mol/L AVP, 10-8-10-5 mol/L Sim dosedependently decreased the expression of cav1 protein. ④The effect of Sim on CFs proliferation and cav1 protein expression was reversed by the addition of MVA. CONCLUSION The inhibitory effect of Sim on proliferation of adult rat CFs induced by AVP may be associated with cav1 expression.

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备注/Memo

备注/Memo:
收稿日期:2007-11-07.基金项目:陕西省自然科技基金项目资助(2004C2-21) 通讯作者:赵连友,教授,主任医师,主要从事高血压发病的分子生物学机制研究Email:zhaolyfmmu@yahoo.com.cn 作者简介:何燕萍,主治医师,博士生Email:hyping@fmmu.edu.cn
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