前胡丙素对Ang II致离体血管平滑肌细胞肥厚及胞内钙、NO含量和信号转导的影响  

EFFECTS OF PRAERUPTORIN C ON CELL HYPERTROPHY, INTRACELLULAR [Ca^(2+)]i , NITRIC OXIDE AND SIGNAL TRANSDUCTION IN ISOLATED HYPERTROPHIED RAT SMOOTH MUSCLE CELLS INDUCED BY ANGIOTENSIN II

作　　者：饶曼人[1] 刘宛斌[1] 张晓文[1] 

机构地区：[1]南京医科大学心血管药理研究室,江苏南京210029

出　　处：《药学学报》2002年第1期5-9,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目 ( 395 70 819)

摘　　要：目的　前胡丙素 (Pra C)对血管紧张素II(AngII)致离体培养大鼠血管平滑肌细胞 (SMCs)肥厚模型胞内游离钙浓度、NO含量和信号转导的影响。方法　以AngII刺激SMCs形成肥厚模型 ,用倒置显微镜测定SMCs面积 ;用Fura 2 AM测定单细胞内 [Ca2 + ]i,Griess法测定NO含量 ;在PMA和ST(PKC激动剂及抑制剂 )、PTX(Gi蛋白敏感毒素 )作用下观察Pra C对KCl和NE所致胞内 [Ca2 + ]i浓度变化的影响。结果　Pra C组SMCs细胞面积较肥厚组减小3 9 0 1% ,并接近正常细胞水平 ;NO含量明显增加 ;胞内 [Ca2 + ]i对KCl和NE激动的反应明显低于肥厚组。PMA使肥厚SMCs [Ca2 + ]i升高 ,而ST及PTX则使之降低 ,Pra C均使之恢复正常。结论　Pra C抑制AngII致体外培养细胞SMCs肥厚 ,改善肥厚细胞因PKC和Gi蛋白的信号转导改变所致的 [Ca2 + ]i改变。AIM To investigate the effects of praeruptorin C (Pra C) on smooth muscle cell (SMC) hypertrophy, intracellular calcium ( [Ca 2+ ]i ), nitric oxide (NO) content and influence on cellular signal transduction in isolated cultured rat smooth muscle cell (SMC). METHODS Hypertrophied smooth muscle cells (HSMCs) were induced by angiotensin II (Ang II), cell area was measured under inverted microscope. Nitric oxide (NO) concentration was measured using Griess method. [Ca 2+ ]i was measured using Fura 2/AM. The responses to [Ca 2+ ]i elevation stimulated by KCl (60 mmol·L -1 or norepinephrine (10 μmmol·L -1 ) were observed by incubation with phorbol 12 myristate 13 acetate (PMA), staurosporine (ST), the agonist and inhibitor of protein kinase C (PKC), and pertussis toxin (PTX), the sensitive toxin of Gi. RESULTS The cell area of SMCs were decreased by 39 01% ( P <0 001) and NO content of SMCs were significantly increased in Pra C + Ang II group. In presence of 60 mmol·L -1 KCl or 10 μmol·L -1 NE, [Ca 2+ ]i of SMCs in Pra C + Ang II group was significantly decreased than that of Ang II group ( P <0 001) and closed to the normal group. Incubation of SMCs with PMA, ST and PTX, [Ca 2+ ]i of SMCs in Ang II group was increased by PMA and decreased by ST and PTX, but that of Pra C + Ang II group was similar to the normal group. CONCLUSION These findings suggest that Pra C can reduce vascular hypertrophy in isolated rat HSMCs, and this is associated with improvment of SMCs [Ca 2+ ]i level, NO content and cellular signal transdution of PKC and Gi.

关 键 词：前胡丙素 血管平滑肌细胞 细胞内游离钙 一氧化氮 信号转导 高血压 左室肥厚 

分 类 号：R544.1[医药卫生—心血管疾病] R541.9[医药卫生—内科学]