文档介绍：NO参与AngⅡ诱导心肌成纤维细胞胶原含量的变化
(作者:___________单位: ___________邮编: ___________)
作者:周有华, 王杨,董战玲,符史干
【摘要】目的:探讨NO前体LArg和NOS抑制剂LNAME在血管紧张素Ⅱ诱导CFs胶原合成中的作用。方法: 用胰酶消化法分离、纯化、培养新生SD大鼠CFs, 采用CFs羟脯氨酸含量测定、以羟脯氨酸标准曲线求出样本中羟脯氨酸含量,胶原含量以羟脯氨酸含量×。结果:(1)在培养液中加入AngⅡ109~105 mol/L,CFs胶原含量呈明显的剂量依赖性;(2)分别给予Saralasin和PTX对CFs胶原含量均无明显影响,但可明显抑制AngⅡ增强CFs胶原含量的作用;(3)预先给予NO前体LArg,再加入AngⅡ,AngⅡ增加CFs胶原含量的效应明显减弱;(4)加入NOS抑制剂LNAME后,再加入LArg和AngⅡ,明显减弱LArg对AngⅡ的抑制作用;(5)在用LNAME抑制NOS的基础上,再加入AngⅡ,其AngⅡ促心脏CFs的作用进一步增强,而单纯应用LNAME对基础状态CFs胶原含量无明显影响。结论:AngⅡ能剂量依赖性增加 CFs胶原含量,此效应是通过AngⅡ受体实现的,可能部分依赖于PTX敏感的G蛋白;NO明显抑制Ang
Ⅱ增加CFs胶原含量的作用,CFs内可能存在LArgNO通路,该通路在调控AngⅡ增加CFs胶原含量中有重要作用。
【关键词】血管紧张素Ⅱ;一氧化氮;心肌成纤维细胞;Saralasin;百日咳毒素;NG硝基左旋精氨酸甲酯
[ABSTRACT] Objective: To investigate the effects of nitric oxide(NO)precursor LArg and NOS inhibitor LNAME on collagen synthesis induced by angiotensin Ⅱ(Ang II) in cardiac fibroblast (CFs). Methods: The CFs of neonatal SD rat were separated, purified and cultured using trypsin digestion method. Hydroxyproline concentration of CFs was determined and calculated by hydroxyproline standard curve, and the collagen concentration was equal to times of hydroxyproline concentration. Results: (1) When adding Ang Ⅱ to the culture solution at the dosage of 10-9 ~ 10-5 mol / L, collagen concentration increased in a dosedependent manner. (2) Saralasin and PTX had no significant effects on collagen concentration of CFs; however, they can inhibit AngⅡ from inducing collagen sythesis in CFs. (3) Adding NO precursor LArg before Ang Ⅱ can significantly weaken the inducing effects of AngⅡ in CFs collagen sythesis. (4)The effects of LArg may be inhibited by pretreatment of L
NAME, a NOS blocker. (5) The inducing effect of Ang Ⅱin CFs collagen sythesis was strengthened by NOS blocker LNAME. Conclusions: These results indicate that collagen concentration of CFs can be significantly increased by Ang Ⅱin a dosedependent manner, which was mediated by Ang Ⅱreceptor and probably may be partiall