摘要
目的探讨缓激肽(BK)在血管紧张素(1~7)[Ang(1~7)]抑制血管紧张素Ⅱ(AngⅡ)诱导的心脏成纤维细胞(CFs)增殖中的作用及其可能机制。方法将差速贴壁法培养的新生大鼠CFs,随机分为5组:对照组、AngⅡ组、Ang(1~7)组、AngⅡ+Ang(1~7)组和AngⅡ+Ang(1~7)+HOE140组。以3H胸腺嘧啶掺入反映细胞增殖情况,通过硝酸还原酶法测定NO含量,放射免疫分析法测定cGMP含量。结果(1)与对照组比,AngⅡ10-7mol/L孵育细胞36h后可明显诱导CFs3H胸腺嘧啶掺入增加,[100%vs51.8%±1.8%,P<0.01]。(2)Ang(1~7)呈浓度依赖性的抑制AngⅡ诱导的CFs3H胸腺嘧啶掺入增加,其Ang(1~7)10-6mol/L可使3H胸腺嘧啶掺入下降至57.9%±2.1%(P<0.01)。(3)与对照组比,AngⅡ组的NO和cGMP含量显著降低(P<0.01),而Ang(1~7)10-6mol/L可显著增加NO和cGMP的含量,与AngⅡ组比,分别上升至177.2%±6.9%、242.3%±19.1%(P<0.01)。(4)缓激肽β2受体阻断剂HOE14010-8mol/L明显减弱了Ang(1~7)抑制CFs增殖和促进CFs释放NO与cGMP的作用,AngⅡ+Ang(1~7)组与AngⅡ+Ang(1~7)+HOE140组比,57.9%±2.1%、177.2%±6.9%、242.3%±19.1%分别转变为88.9%±4.2%、125.7%±8.2%、162.2%±14.7%(P<0.01)。结论Ang(1~7)可能通过与BK相互作用促进NO和cGMP的产生,从而抑制AngⅡ诱导的CFs的增殖。
Objective To explore the potential role of bradykinin (BK) in the inhibitory effect of angiotensin (1-7) on the proliferation of cardiac fibroblasts induced by angiotensin (Ang Ⅱ). Methods Neonatal rat cultured cardiac fibroblasts were randomly divided into 5 groups: control, Ang Ⅱ, Ang(1-7) , Ang Ⅱ+Ang(1-7) , and Ang Ⅱ+Ang(1-7) +HOE-140. Fibroblasts proliferation was assessed by thymidine incorporation. Production of nitric oxide (NO) was determined by the nitric acid reductase method, and production of cGMP by radiommunoassay. Results (1) After incubating the fibroblasts with 10~ -7 mol/L Ang Ⅱ for 36 hours, thymidine incorporation was significantly increased compared with control (100% vs 51.8%±1.8%, P <0.01). (2) 10~ -6 mol/L Ang(1~7) inhibited Ang Ⅱ induced fibroblasts proliferation in a dose-dependent manner, lowering the value of thymidine incorporation to 57.9%±2.1% (P<0.01) . (3)Ang Ⅱ decreased NO and intracellular cGMP as compared with control (P< 0.01). However, 10~ -6mol/L Ang(1-7) significantly increased NO and intracellular cGMP to 177.2%±6.9%, 242.3%±19.1%, respectively. (4) The BK subtype 2 receptor antagonist HOE-140 attenuated the inhibitory effect on the proliferation of fibroblasts induced by Ang Ⅱand also blunted the increase in NO and cGMP in response to Ang(1-7) . Conclusion The interaction between Ang(1-7) and BK, resulting in increased production of NO and cGMP, might be involved in the process which Ang(1-7) inhibits the proliferation of cultured cardiac fibroblasts induced by Ang Ⅱ.=
出处
《高血压杂志》
CSCD
北大核心
2005年第4期226-230,共5页
Chinese Journal of Hypertension