去纤酶的抗血管紧张素Ⅱ促血管平滑肌细胞增殖作用

Effect of Defibrinogenase to Antagonize Proliferation Stimulating Effect of Angiotensin Ⅱ on Aortic Smooth Muscle Cells

为寻找新型药物以拮抗血管紧张素Ⅱ（AⅡ）的促增殖作用,本应用3H-TdR 参入、反转录一聚合酶链反应（RT-PCR）及放射免疫实验技术,研究了蛇毒去纤酶对 AⅡ刺激下的卒中易感型自发性高血压大鼠（SHRsp）及 WKY 大鼠主动脉平滑肌细胞（ASMC）增殖的影响及其机制。结果:去纤酶（0.5U/L）能明显抑制 AⅡ、血小板源生长因子（PDGF）及 AⅡ与 PBGF共同刺激的 ASMC 中 DNA 的合成（抑制率分别为 SHRsp:48.7％,19.2％,28.0％;WKY 大鼠: 28.5％,16.1％,22.9％）;能降低 ASMC 内 AⅡ含量（SHRsp 降低46％,WKY 大鼠降低15％）。但它不能抑制 AT1受体 mRNA 的表达,推测其抑制 ASMC 增殖可能是通过抑制了 PDGF 介导的胞内信息传递。比较去纤酶对两种大鼠 ASMC 增殖的抑制效率,发现其对 SHRsp ASMC 抑制作用更强。

To seek for a new type of drug to antagonize the proliferation stimulating effects of angiotension Ⅱ （AⅡ）,the effect of de- fibrinogenase on the proliferation stimulating effect of AⅡ on aortic smooth muscle cells （ASMC） from stroke-prone spontaneous- ly hypertensive rats （SHRsp） and their normotensive comtrol Wistar Kyoto （WKY） rats were studied with 3H-TdR incorporation, reverse transcription polymerase chain reaction （RT-PCR） and radioimmunoassay.The results showed that defibrinogenase sig- nificantly inhibited the DHA synthesis of ASMC stimulated by AⅡ,platelet-derived growth factor （PDGF） and both of them （decreased 48,7%,19.2% and 28.0% in SHRsp,or 28.5%,16.1% and 22.9% in WKY rats respectively）.Further more,it decreased the AⅡ contents in ASMC （decreased 46% in SHRsp and 15% in WKY rats）,but it could not inhibit the expression of AT1 mRNA.So its inhibitory effect on ASMC proliferation probably is due to the inhibition of the intracellular signal transduction induced by PDGF.Comparing the inhibitory effect of defibrinogenase on ASMC from both strains of rats,it seems stronger on SHRsp ASMC than that on WKY rats.