血管紧张素Ⅱ上调乳鼠心室肌细胞TRPC1通道的表达  

Upregulation of TRPC1 Expressions in Cardiomyocytes Induced by Angiotensin Ⅱ

作　　者：马前军[1] 杨向军[1] 韩莲花[1] 李红霞[1] 

机构地区：[1]苏州大学附属第一医院心内科,江苏苏州215006

出　　处：《苏州大学学报（医学版）》2011年第3期433-436,共4页Suzhou University Journal of Medical Science

摘　　要：目的观察血管紧张素Ⅱ(AngⅡ)刺激心肌细胞,导致经典瞬时受体电位(TRPC)通道1表达的改变情况,并探讨其机制。方法分离和培养原代乳鼠心室肌细胞,运用Western blot法检测细胞TRPC1、TRPC3和TRPC6蛋白的表达,3H-亮氨酸掺入法测定细胞蛋白质合成速率。结果 AngⅡ能刺激心肌细胞TRPC1表达显著上调(P<0.01),心肌细胞TRPC1的表达随AngⅡ浓度增加而逐渐明显上调;但AngⅡ刺激并未明显增高TRPC3和TRPC6蛋白的表达(P>0.05)。给予AT1受体拮抗剂氯沙坦、磷脂酶C(PLC)抑制剂U73122、钙池操作性钙内流阻滞剂SKF96365或钙调神经磷酸酶抑制剂环孢素A预处理后,都能抑制AngⅡ引起的TRPC1高表达(均P<0.05),但AT2受体拮抗剂PD123319却不能。SKF96365预处理在能明显抑制AngⅡ引起的TRPC1高表达的同时,也能抑制AngⅡ诱导的细胞肥大。结论 AngⅡ诱导大鼠心室肌细胞TRPC1表达上调并呈现剂量依赖性,这种上调是通过AT1R/PLC信号传导,激活钙调神经磷酸酶途径来实现的。Objective To investigate the expression changes of canonical transient receptor potential（TRPC） in cultured cardiomyocytes induced by angiotensin Ⅱ（Ang Ⅱ）.Methods The cardiomyocytes of neonatal rats were separated and cultured.The expressions of TRPC1,TRPC3 and TRPC6 were detected by Western blot analysis,and protein synthesis rate in cultured cardiocytes was determined by the 3H-leucine incorporation.Results The expression of TRPC1 was upregulated after a 48 h treatment with Ang Ⅱ,and increased with the increase of the concentration of AngⅡ;but the expression of neither TRPC3 nor TRPC6 was markedly upregrated at the same time.AngⅡ-induced upregulation of TRPC1 was decreased by treated with U73122（a phospholipase C inhibitor）,SKF96365（a store-operated channel blocker）,cyclosporin A（a calcineurin inhibitor）,and losartan（an Ang Ⅱ type 1 receptor blocker）,but not decreased by treated with PD123319（an Ang Ⅱ type 2 receptor blocker）.Hypertrophy of cardiomyocytes induced by AngⅡ was suppressed by SKF96365.Conclusion The upregulation of TRPC1 in cardiomyocytes induced by Ang Ⅱ presents dose-dependent relationship.The upregulation is completed through AT1R/PLC signal conduction and activation of calcineurin signaling.

关 键 词：经典瞬时电位通道 心肌细胞 肥大 血管紧张素Ⅱ 

分 类 号：R542.2[医药卫生—心血管疾病]