应用干扰素-α减弱大鼠血管内皮依赖性的舒张作用

目的 :研究急、慢性干扰素 - α(IFN- α)处理对离体大鼠胸主动脉环的影响及其可能机制。方法 :用离体血管灌流方法 ,测定离体主动脉环张力。结果 :IFN- α(10、10 0、10 0 0、10 0 0 0 U/ ml)对苯肾上腺素 (PE,10 -6mol/ L)预收缩的内皮完整血管环产生浓度依赖性的舒张作用 ,分别降低为对照的 (90 .1± 0 .91) %、(6 5 .1± 5 .2 1) %、(39.5± 8.2 2 ) %、(35 .3± 8.2 7) %。去除内皮后 IFN- α的舒张作用被取消。用一氧化氮合酶 (NOS)抑制剂 L- NAME(10 -4mol/ L)、鸟苷酸环化酶抑制剂亚甲蓝 (10 -5mol/ L)和诱导型 NOS抑制剂 AMG(10 -4mol/ L)预处理后 ,10 0 U/ mlIFN- α引起的血管舒张作用被阻断 ,其血管舒张幅度分别为对照的 (97.2± 5 .34) %、(95 .1± 6 .2 5 ) %、(93.7±8.82 ) %。用 IFN- α10 0 0 0 U/ ml预处理 2 h对 Ach引起的内皮依赖性主动脉环的舒张作用无显著影响 ,用IFN- α10 0万 U/ d腹腔注射 5 d后的 SD大鼠的主动脉环对 Ach引起的内皮细胞依赖性舒张作用明显降低。结论 :IFN- α可能通过诱导 i NOS合成或增强 i NOS其活性产生内皮依赖的血管舒张作用 ,慢性 IFN-α处理可能损害了血管内皮的功能或使 NO- s GC信号途径的效能降低。

Treatment of interferon-α in reducing the endothelium-dependent relaxation of rat thoracic aorta

OBJECTIVE: To investigate the vascular effect of acute and chronic treatment of interferon-alpha (IFN-alpha) in rat aortic rings. METHODS: Isolated thoracic aortic rings were mounted on the organ bath and the tension of the vessel was recorded. RESULTS: IFN-alpha(10, 100, 1,000 and 10,000 U/ml) caused concentration -dependent relaxation of endothelium-intact aorta rings preconstricted with phenylephrine (PE,10(-6)mol/L), to(90.1+/-0.91)%, (65.1+/-5.21)%, (39.5+/-8.22)% and (35.3+/-8.27)% of pre-drug control, respectively. Removal of the endothelium inhibited the relaxation by IFN-alpha. The vasorelaxant effect of IFN-alpha (100 U/ml ) was attenuated by pretreatment with L-NAME (10(-4)mol/L), methylene blue (10(-5)mol/L) or AMG (10(-4)mol/L), to (97.2+/-5.34)%, (95.1+/-6.25)% and (93.7+/-8.82)% of the control, respectively. Pretreatment with IFN-alpha (1,000,000 U/d, i.p.) for five days markedly inhibited the endothelium-dependent relaxation of the aortic rings to acetylcholine. But the endothelium-dependent relaxation to acetylcholine was not changed by pretreatment of IFN-alpha (10,000 U/ml) with the isolated aorta rings for 2 h. CONCLUSION: The vasorelaxation induced by IFN-alpha in rat aorta rings is endothelium-dependent and is possibly mediated by inducible nitric oxide synthase. Chronic treatment of IFN-alpha may impair the endothelium or NO-sGC pathway.