多聚肌苷酸在兔动物模型中抗动脉粥样硬化的作用及对血管组织LOX-1表达的影响

Effect of polyinosinic acid on expression of lectin-like oxidized low-density lipoprotein receptor-1 and its antiatherogenic role in atherosclerotic rabbits

目的探讨多聚肌苷酸在兔动物模型中抗动脉粥样硬化(AS)的作用以及对血凝素样氧化低密度脂蛋白-1(LOX-1)表达的抑制作用。方法 30只雄性新西兰大白兔随机分为普通饲料喂养组(对照组n=6)、球囊拉伤后高脂饲料喂养组(高脂组n=6)、球囊拉伤后高脂饲料+氟伐他汀喂养组(他汀组n=6)、球囊拉伤后高脂饲料喂养+多聚肌苷酸(polyⅠ)肌注组(polyⅠ组n=6)和球囊拉伤后高脂饲料+氟伐他汀喂养+polyⅠ肌注组(联合组n=6)。除对照组外,其余各组兔均在3%质量浓度的戊巴比妥钠全麻下经股动脉行腹主动脉球囊拉伤术损伤动脉内膜,术后开始给予高脂饲料喂养制备AS模型。各组动物均喂养12周,喂养同时每天分别给予polyⅠ[1%的质量浓度1 mL/(kg.d)]肌肉注射和氟伐他汀[10 mg/(kg.d)]喂养干预。12周后处死动物取其腹主动脉观察病理变化,用逆转录聚合酶链反应(RT-PCR)测定LOX-1 mRNA的表达;免疫组化测定LOX-1蛋白的表达。结果各组兔腹主动脉组织病理学变化:①对照组动脉血管内膜内皮细胞完整,无明显脂质沉淀;②高脂组动脉血管内膜内皮细胞脱落,可见粥样斑块形成,纤维帽下含大量无定形的坏死崩解产物,其内含大量胆固醇结晶、泡沫细胞和少量淋巴细胞;③他汀组AS程度较高脂组明显减轻,内皮细胞部分脱落,内膜下散在不规则隆起的斑块,可见数量不等的泡沫细胞;④PolyⅠ组较高脂组AS程度亦减轻,血管内膜内皮细胞部分脱落,血管可见纤维斑块和粥样斑块并存,斑块表面有纤维组织覆盖,内膜纤维帽下含大量泡沫细胞,并伴炎细胞浸润;⑤联合组病变较高脂组减轻最明显,内膜稍增厚,可见少量泡沫细胞,内弹力板完整,中膜平滑肌排列整齐。对照组兔腹主动脉血管组织中有少量的LOX-1蛋白及mRNA的表达;高脂组较其他组表达最为明显,他汀组以及联合组LOX-1蛋白和mRNA的表达较高脂组均明显减少(P均<0.01),PolyⅠ组LOX-1蛋白和mRNA的表达与高脂组差异无统计学意义(P>0.05)。结论 PolyⅠ可能具有一定的抗AS发生发展的作用,但PolyⅠ抑制LOX-1蛋白和mRNA表达的作用不显著。氟伐他汀抗AS的同时可明显地抑制血管AS斑块中LOX-1蛋白及mRNA的表达。

Objective To explore inhibitory actions of polyinosinic acid on expression of lectin-like oxidized low-density lipoprotein receptor-1 and its antiatherogenic role in atherosclerotic rabbits.Methods Thirty male New Zealand white rabbits were randomly divided into five groups： the control group,the hypercholesterol group,the poly Ⅰ group,the fluvastatin group and the association group（n=6）.Except for the control group,the other groups were strained with a balloon in the abdominal aortic under general anesthesia induced by 3% sodium pentobarbital.Then,they were fed with polyinosinic acid（polyⅠ）,fluvastatin,or hypercholesterol.12 weeks later,rabbits were sacrificed and the abdominal aortas were pathologically studied.Expressions of LOX-1 mRNA and protein in the vascular tissue were determined by immunohistochemistry and reverse transcription-polymerase chain reaction（RT-PCR）,respectively.Results Pathological changes of abdominal aortas： ① In the control group,ascular intima endothelial cells were intact and had no obvious lipid deposition.② In the hyper-cholesterol group,vascular intima endothelial cells fell off and atheromatous plaque formation were identified.Under the fibrous cap,large numbers of amorphous necrotic disintegrating products could be found with large amounts of cholesterol clefts,foam cells and lymphocytes.③ In the fluvastatin group,some endothelial cells fell off.Beneath the vascular intima,there were scattered and irregular plaques with a small amount of foam cells.④ In the poly Ⅰ group,some endothelial cells fell off and there were a lot of foam cells,as well as inflammatory cells,below the fibrous cap.⑤ In the association group,there was obviously weaker atherosclerosis than in the hypercholesterol group.The ascular intima slightly thickened,and there were a few foam cells,with the smooth muscle tidily ranked.There were high expressions of LOX-1 protein and mRNA in the vascular tissues of the hyper-cholesterol group,but rarely in the control group.Expression of LOX-1 protein and mRNA in both the fluvastatin group and association group were significantly lower than that in the hypercholesterol group（P〈0.01）.Expressions of LOX-1 protein and mRNA between the hyper-cholesterol group and polyⅠgroup showed no significance（P〉0.05）.Conclusion Poly Ⅰ may have a role in resist ance of atherosclerosis,but it does not posses an obvious function to reduce expressions of LOX-1 protein and mRNA.Fluvastatin can significantly inhibit the development of atherosclerosis and expressions of LOX-1 protein and mRNA.