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拉西地平对AVP诱导的大鼠心脏成纤维细胞增殖的影响及其与ERK1/2的关系(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2008年第2期
页码:
132-135
栏目:
基础研究
出版日期:
2008-03-20

文章信息/Info

Title:
Effects of lacidipine on cell proliferation of CFs induced by AVP and its relationship with ERK1/2
作者:
陆小龙赵连友郑强荪赵小燕何艳萍刘慧尚福军
第四军医大学唐都医院心内科,陕西 西安 710038
Author(s):
LU Xiaolong ZHAO Lianyou ZHENG QiangsunZHAO Xiaoyan HE Yanping LIU Hui SHANG Fujun
Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi, China
关键词:
血管加压素拉西地平心脏成纤维细胞增殖ERK1/2大鼠
Keywords:
vasopressin lacidipine cardiac fibroblastsproliferationERK1/2rats
分类号:
R972
DOI:
-
文献标识码:
A
摘要:
目的 观察拉西地平对血管加压素(AVP)诱导的大鼠心脏成纤维细胞(CFs)增殖的影响及其与细胞外信号调节激酶(ERK)1/2的关系。方法 以培养的新生SD大鼠CFs为实验模型,采用四氮唑盐比色法测定细胞数目;用流式细胞术分析细胞周期;用蛋白免疫印迹法测定总细胞外信号调节激酶(tERK)1/2和磷酸化细胞外信号调节激酶(pERK)1/2在细胞内的表达。实验按照给予CFs干预因素的不同,分为对照组、10-7mol/L AVP处理组、10-9~10-6 mol/L拉西地平+10-7mol/L AVP干预组和10-7mol/L拉西地平单独干预组。 结果 ①10-7mol/L AVP干预24 h后,CFs的A490值(0.232±0.013)较对照组(0.132±0.008)显著增高(P<0.01)。在10-9~10-6 mol/L拉西地平和10-7mol/L AVP共同干预下,拉西地平可呈浓度依赖性地下调CFs的A490值,分别为0.216±0.01、0.203±0.01、0.176±0.01和0.160±0.01,均显著低于AVP组(P<0.01)。②细胞周期分析显示,AVP组CFs 在S期的百分率和增殖指数(PI)分别为13.06±0.83和21.70±1.55,与对照组(分别为4.60±0.60和8.97±1.56)比较显著增高(P<0.01)。在10-7mol/L 拉西地平干预下,细胞在S期的百分率(8.84±0.80)和PI (15.46±1.84)较AVP组显著降低 (P<0.01)。 ③AVP组CFs的pERK1/2表达显著高于对照组(P<0.01),10-9、10-8、10-7和10-6mol/L拉西地平组CFs中pERK1/2的表达与AVP组比较呈浓度依赖性地降低(P<0.01)。 结论 拉西地平可抑制AVP诱导的大鼠CFs增殖,提示拉西地平对预防和逆转心脏重构具有一定的作用,其机制可能与ERK1/2的磷酸化有关。
Abstract:
AIM To study the effect of Lacidipine on cell proliferation of cardiac fibroblasts (CFs) induced by vasopressin (AVP) and its relationship with ERK1/2. METHODS CFs were isolated and cultured from neonatal SD rats and the CFs were divided into four groups: control group, 10-7mol/L AVP group, 10-9-10-6 mol/L Lacidipine+10-7mol/L AVP group and 10-7mol/L Lacidipine group. Cell number and cell cycle were evaluated by MTT assay (A value) and flow cytometry technique and Western blot was used to study the protein expression level of tERK1/2 and pERK1/2. RESULTS ①10-7mol/L AVP significantly increased A value of CFs (0.232±0.013) in comparison with that in control group (0.132±0.008,P<0.01). Lacidipine in the range of 10-9-10-6 mol/L attenuated the A value of AVP group in a concentration dependent manner (0.216±0.01、0.203±0.01, 0.176±0.01 and 0.160±0.01, P<0.01).②Compared with those in the control (4.60±0.60 and 8.97±1.56), cells in S stage (13.06±0.83) and proliferation index (21.70±1.55) markedly increased by 10-7mol/L AVP (P<0.01, respectively). In the presence of 10-7mol/L Lacidipine, cells in S stage (8.84±0.80) and the proliferation index (15.46±1.84) were significantly lower than those in AVP group (P<0.01, respectively). ③The protein level of pERK1/2 in AVP group was significantly higher than that in control group (P<0.01). Lacidipine in the range of 10-9-10-6 mol/L attenuated the protein level of pERK1/2 of AVP group in a concentration dependent manner (P<0.01, respectively). CONCLUSION Lacidipine, which effectively inhibits the cell proliferation of CFs induced by AVP, may play some roles in the prevention and reversion of cardiac remodeling. The mechanism of the effect may be related to the phosphorylation of ERK1/2.

参考文献/References

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备注/Memo

备注/Memo:
收稿日期:2008-01-09.基金项目:陕西省自然科技基金资助项目(2004C2-21) 通讯作者:赵连友,教授,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:陆小龙,医师,硕士生Email:luxlfmmu@yahoo.cn
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