α-2b干扰素抑制动脉粥样硬化的实验研究

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＜0.05),AS组小于V组(P＜0.05)。NC组、IFN-Ⅰ组、IFN-Ⅱ组PDGF-B的表达低于AS组、V组(P＜0.05)。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。

Inhibitory effect of interferon α-2b on atherosclerosis

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 controlgroup(NCgroup,n＝6),atherosclerosisgroup(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.