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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 investigate the role of polyinosinic acid in anti-atherosclerosis (AS) and the inhibition of the expression of cyclooxygenase-1 (LOX-1) in rabbit animal models. Methods Thirty male New Zealand white rabbits were randomly divided into normal feed group (n = 6 in control group), high fat diet group (n = 6 in high fat diet group), high fat diet + Fluvastatin group (n = 6 in statin group), high fat diet group (n = 6 in polyⅠ group) and high fat diet group + Fluvastatin + polyI intramuscular injection group (combination group n = 6). Except for the control group, the rabbits in other groups were all injured by the abdominal aortic balloon injury through the femoral artery under the general anesthesia of sodium pentobarbital with 3% concentration. The rabbits were given high-fat diet after the start of the operation AS model. Animals in each group were fed for 12 weeks, and fed with polyⅠ [1% (mass concentration 1 mL / (kg · d)] intramuscularly and fluvastatin [10 mg / (kg · d)] respectively during feeding. After 12 weeks, the animals were sacrificed and their abdominal aorta was taken for pathological changes. The expression of LOX-1 mRNA was determined by reverse transcription-polymerase chain reaction (RT-PCR) and the expression of LOX-1 protein by immunohistochemistry. Results The pathological changes of the abdominal aorta of rabbits in each group were as follows: ① The endothelium of the arterial endothelium of the control group was intact with no obvious lipid deposition; ② The endothelium of the arterial endothelium of the hyperlipidemic group shedding, showing the formation of atherosclerotic plaque, Which contains a large amount of amorphous necrosis products of disintegration, which contains a large number of cholesterol crystals, foam cells and a small amount of lymphocytes; ③ statin AS group was significantly lower than the high-fat group, endothelial cells were partially exfoliated scattered in the irregular Plaque, the number of visible foam cells; ④Poly Ⅰ group than in the high-fat group also reduce the degree of AS, vascular endothelial cells partially shedding, blood vessels visible plaque and plaque coexist plaque surface covered with fibrous tissue, There were a large number of foam cells in the endometrial fibrous cap and infiltration of inflammatory cells. ⑤ The lesions in the combined group were relieved more significantly than those in the hyperlipidemic group, while the intima slightly thicken. A small amount of foam cells were observed. The inner elastic plate was intact and the smooth muscle in the tunica media arranged neatly. The expression of LOX-1 protein and mRNA in the abdominal aorta of rabbits in the control group was the lowest. The expression of LOX-1 protein and mRNA in the hyperlipidemia group was more obvious than that in the other groups (P <0.01). The expression of LOX-1 protein and mRNA in PolyⅠgroup was not significantly different from that in hyperlipidemia group (P> 0.05). Conclusion Poly Ⅰ may play a role in anti-AS development, but Poly I inhibits LOX-1 protein and mRNA expression is not significant. Fluvastatin anti-AS can significantly inhibit the expression of LOX-1 protein and mRNA in vascular AS plaques.