α-2b干扰素抑制动脉粥样硬化的实验研究

Inhibitory effect of interferon α-2b on atherosclerosis

目的 :探讨α - 2b干扰素 (IFNα- 2b)抑制动脉粥样硬化 (AS)的体内机制。方法 :随机将家兔分为空白对照 (NC)组、动脉粥样硬化 (AS)组、病毒感染动脉粥样硬化 (V)组、干扰素治疗非病毒感染动脉粥样硬化 (IFN -Ⅰ )组、干扰素治疗病毒感染动脉粥样硬化 (IFN -Ⅱ )组。复制AS模型 ,于第 1、3、5、7周酶法测血清总胆固醇、甘油三脂。 7周后主动脉苏丹Ⅳ染色测AS斑块面积 /总面积 ,HE染色观察主动脉形态学改变。用免疫组化法测胸主动脉中的增殖细胞核抗原 (PCNA)和单纯疱疹病毒Ⅰ型 (HSV -Ⅰ )的表达 ,用原位杂交法测血小板衍生生长因子 β(PDGF - β)的表达程度。 结果 :NC组、IFN -Ⅰ组、IFN -Ⅱ组主动脉粥样硬化斑块面积小于AS组 (P <0 .0 5) ,AS组小于V组 (P <0 .0 5)。NC组、IFN -Ⅰ组、IFN -Ⅱ组PDGF -B的表达低于AS组、V组 (P <0 .0 5)。结论 :病毒可能是AS的始动因素 ,PDGF - β可能是促使血管平滑肌细胞 (VSMC)增生、AS进展的主要因素。IFNα- 2b通过抑制病毒和下调PDGF - βmRNA抑制VSMC的增生 ,可能是其抑制AS的形成及发展的重要机制之一。

AIM: To evaluate the effects of interfer α-2b (IFN α-2b ) on atherosclerosis(AS).METHODS: Thirty normal male rabbits were randomly divided into five groups:normal control group(NC group, n= 6), atherosclerosis group(AS group, n =6),virus (herpesvirus Ⅰ,HSV-Ⅰ)infected atherosclerosis group(V group, n= 6), interferon (interferon α-2b) intervented atherosclerosis group (IFN-Ⅰgroup, n= 6),interferon intervented and virus infected atherosclerosis group (IFN-Ⅱ group, n= 6). Serum lipids were measured and the thoracic aortas were sampled for histopathological, immunohistochemical and in situ hybridization study. RESULTS: The aorta atherosclerosis areas of NC, IFN-Ⅰ and IFN-Ⅱ groups were lower than that of AS group significantly, respectively, and the area of AS group was lower than that of V group ( P< 0.05). Platelet-derived growth factor B-chain (PDGF-β) expression was reduced both in IFN-Ⅰand IFN-Ⅱ groups( P< 0.05). CONCLUSIONS: Our data provide evidence that virus could cause atherosclerosis, and the AS formation could be inhibited by IFN α-2b through its antivirus effect and inhibitory effect on PDGF-β and VSMC proliferation.