瑞舒伐他汀对内皮素1诱发肥大心肌细胞中[^(14)C]苯丙氨酸结合的影响研究  

Influence of Rosuvastatin over Phenylalanine Coordination in Hypertrophic Cardiomocytes Induced by Endothelin- 1

作　　者：王新[1] 锦见俊雄 

机构地区：[1]首都医科大学附属北京安贞医院北京市心肺血管疾病研究所心内科,北京市100029 [2]日本独协医科大学病院循环器内科

出　　处：《中国全科医学》2014年第15期1739-1743,1751,共6页Chinese General Practice

摘　　要：目的探讨瑞舒伐他汀是否对体外内皮素1诱发的肥大心肌细胞有直接的抑制作用,并研究瑞舒伐他汀影响肥大心肌细胞的机制。方法富集培养的新生大鼠心肌细胞,一部分加入内皮素1(0、10-7mol/L)分别制备正常心肌细胞和肥大心肌细胞,加入瑞舒伐他汀〔0(对照组)、10-9、10-8、10-7、10-6mol/L〕和普伐他汀〔0(对照组)、10-9、10-8、10-7、10-6mol/L〕培养24 h。一部分加入甲羟戊酸(10-6~10-4mol/L)、角鲨烯(10-6~10-4mol/L)、法尼基-焦磷酸(FPP)(10-7~10-5mol/L)、牛儿-焦磷酸(GGPP)(10-7~10-5mol/L)预培养6~12 h,再添加内皮素1(0、10-7mol/L)和瑞舒伐他汀(10-6mol/L)培养。另一部分加入C3胞外酶(0、2.5、12.5、25.0μg/ml)和Y27632(0、10-7、10-6、10-5mol/L)预培养6~12 h,再添加内皮素1(10-7mol/L),分别检测[14C]苯丙氨酸(Phe)结合率。结果对照组与不同浓度瑞舒伐他汀组正常心肌细胞[14C]Phe结合率比较,差异有统计学意义(F=21.58,P<0.05);其中10-6mol/L组正常心肌细胞[14C]Phe结合率较其他4组下降(P<0.05)。对照组与不同浓度瑞舒伐他汀组肥大心肌细胞[14C]Phe结合率比较,差异有统计学意义(F=21.12,P<0.05);其中10-6mol/L组肥大心肌细胞[14C]Phe结合率较其他4组下降(P<0.05)。对照组与不同浓度普伐他汀组正常心肌细胞和肥大细胞[14C]Phe结合率比较,差异无统计学意义(F值分别为19.24和18.65,P>0.05)。甲羟戊酸处理:对照组、空甲羟戊酸组、10-6mol/L组、10-5mol/L组、10-4mol/L组心肌细胞[14C]Phe结合率较空瑞舒伐他汀组降低,10-4mol/L组心肌细胞[14C]Phe结合率较对照组、空甲羟戊酸组、10-6mol/L组、10-5mol/L组升高(P<0.05)。角鲨烯处理:对照组、空角鲨烯组、10-6mol/L组、10-5mol/L组、10-4mol/L组心肌细胞[14C]Phe结合率较空瑞舒伐他汀组降低(P<0.05)。FPP处理:对照组、空瑞舒伐他汀组、空FPP组、10-6mol/L组、10-5mol/L组、10-4mol/L组心肌细胞[14C]Phe结合率比较,差异无统�Objective To determine whether rosuvastatin has a direct inhibitory effect on myocyte hypertrophy induced by endothelin- 1 in vitro and to investigate the mechanism by which rosuvastatin affects myocyte hypertrophy.Methods enriched cultures of neonatal cardiac myocytes,after a preconditioning period,with various concentrations of endothelin- 1,rosuvastatin,pravastatin,mevalonate,squalene,FPP,GGPP,C3 exoenzyme and Y- 27631 were added,and [14C] Phe was also added.The effect of various agents on protein synthesis in cultured cardiac myocytes was evaluated by measuring the combined rate of [14C] Phe into cells.Results [14C] Phe combined rate in different concentrations of rosuvastatin group treated normal and hypertrophic cardiac myocytes were statistically different from that in control group（F = 21.58,21.12,P〈0.05）;That were statistically decreased in 10- 6mol /L rosuvastatin compared with other four groups（P〈0.05）.[14C] Phe combined rate in various concentrations of pravastatin treated normal and hypertrophic cardiac myocytes had no statistically significant difference in comparison with that in control group（F = 19.24,18.65,P 〉0.05）.[14C] Phe combined rate in 10- 4mol /L mevalonate treated hypertrophic cardiac myocytes was increased compared with control group,mevalonate free group and 10- 6mol /L,10- 5mol /L group（P〈0.05）.[14C] Phe combined rate in 10- 4mol /L squalene treated hypertrophic cardiac myocytes was significantly increased in comparison with control group,squalene free group and 10- 6mol /L and 10- 5mol /L group（P〈0.05）.There were no significant difference in [14C] Phe combined rate between control group,FPP free group,10- 6mol /L,10- 5mol /L,10- 4mol /L group（F = 10.07,P = 0.14）.There were no significant difference in [14C] Phe combined rate between control group,GGPP free group,10- 6mol /L,10- 5mol /L,10- 4mol /L group（F = 10.42,P = 0.11）.[14C] Phe combined rate in different concentrations C3 exoenzyme and Y27632 treated hypertrophic cardiac myocytes were statis

关 键 词：瑞舒伐他汀 内皮素1 肥大 肌细胞 心脏 

分 类 号：R542.2[医药卫生—心血管疾病]