CAJ | 학술논문

目的：观察腹主动脉粥样斑块内炎性巨噬细胞和平滑肌细胞的表达情况，以探索依折麦布联合他汀类药物在逆转动脉斑块中的作用及机制。方法选取24只健康雄性新西兰大耳白兔，随机分为对照组（n＝8）和高胆固醇血症组（n＝16）。对照组给予普通饲料，喂养12周。高胆固醇血症组喂饲致动脉粥样硬化饲料（由普通颗粒饲料＋15g/L胆固醇＋100g/L猪油＋150g/L蛋黄粉组成）2周后行腹主动脉内膜球囊拉伤术，术后再随机分为模型亚组和依折麦布辛伐他汀（ES）亚组（给予5/10mg/（kg·d）每组8只，两亚组均继续喂饲致动脉粥样硬化饲料10周。喂养第12周时活杀动物，取腹主动脉进行石蜡切片。检测不同时间点脂质和脂蛋白，应用光学显微镜观察动脉粥样硬化进程，采用免疫组化方法分析巨噬细胞和平滑肌细胞在斑块处的表达。结果 ES亚组的血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）浓度明显低于模型亚组（P＜0.01）。病理检测显示两亚组及ES亚组斑块直径、斑块厚度和动脉内/中膜厚度经单因素方差分析，差异有统计学意义（P＜0.05）。免疫组化检测结果示ES亚组血管壁中巨噬细胞的表达量较模型亚组显著减少（P＜0.05），而平滑肌细胞的表达量较模型亚组显著增多（P＜0.01）。结论 ES可能通过减少细胞外脂质的沉积，减少内膜和中膜巨噬细胞的数量和胆固醇的含量，增加胶原和平滑肌细胞面积，从而起到逆转斑块的作用。
목적：관찰복주동맥죽양반괴내염성거서세포화평활기세포적표체정황，이탐색의절맥포연합타정류약물재역전동맥반괴중적작용급궤제。방법선취24지건강웅성신서란대이백토，수궤분위대조조（n＝8）화고담고순혈증조（n＝16）。대조조급여보통사료，위양12주。고담고순혈증조위사치동맥죽양경화사료（유보통과립사료＋15g/L담고순＋100g/L저유＋150g/L단황분조성）2주후행복주동맥내막구낭랍상술，술후재수궤분위모형아조화의절맥포신벌타정（ES）아조（급여5/10mg/（kg·d）매조8지，량아조균계속위사치동맥죽양경화사료10주。위양제12주시활살동물，취복주동맥진행석사절편。검측불동시간점지질화지단백，응용광학현미경관찰동맥죽양경화진정，채용면역조화방법분석거서세포화평활기세포재반괴처적표체。결과 ES아조적혈청총담고순（TC）、감유삼지（TG）、저밀도지단백담고순（LDL-C）농도명현저우모형아조（P＜0.01）。병리검측현시량아조급ES아조반괴직경、반괴후도화동맥내/중막후도경단인소방차분석，차이유통계학의의（P＜0.05）。면역조화검측결과시ES아조혈관벽중거서세포적표체량교모형아조현저감소（P＜0.05），이평활기세포적표체량교모형아조현저증다（P＜0.01）。결론 ES가능통과감소세포외지질적침적，감소내막화중막거서세포적수량화담고순적함량，증가효원화평활기세포면적，종이기도역전반괴적작용。
ObjectiveTo observe the efficiency of ezetimibe/simvastatin (ES) tablets on the regression of atherosclerotic plaque of abdominal arteries in rabbits.Methods Twenty-four healthy male New Zealand rabbits were randomly divided into 2 groups: control group (n=8) and hypercholesterolemia group (n=16). Control group was fed with normal diet for 12 weeks. The other group animals were given a cholesterol-supplemented diet (normal diet+15g/L cholesterol+100g/L lard+150g/L egg yolk powder) for 2 weeks, and underwent catheter-induced arterial wall injury. These rabbits were then randomized to model subgroup (n=8, for another 10 weeks of hypercholesterol diet) and ES treatment subgroup [n=8, 5/10mg/(kg·d) for another 10 weeks]. Chinese russell’sviper venom was intra-peritoneally injected to trigger plaque rupture. Abdominal aortagraphy was carried out to measure the aorta stenosis. After 12 weeks’ feeding, all rabbits were sacrificed, and their abdominal arteries were isolated, paraffin-embedded and then sectioned. Blood lipid and lipoproteins were detected. The development of the atherosclerotic plaques was evaluated through the light microscopy. Finally, the expression of macrophage and smooth muscle actin in the abdominal arteries was measured by immunohistochemical analysis.Results The serum levels of total cholesterol (TC), triglycerides (TG) and low density lipoprotein-cholesterol (LDL-C) were significantly lower in the ES treatment subgroup than in the hypercholesterolemia model group (P<0.01). One-way analysis of variance indicated that significant differences were found in the plaque diameter, plaque thickness and the intimal-medial thickness between the ES subgroup and hypercholesterolemia model subgroup by morphological observation (P<0.05). Immunohistochemical analysis showed that lesser macrophages (P<0.05) but more smooth muscle cells (P<0.01) were found in the ES treatment subgroup than in the model group.Conclusion It may be through reducing the deposition of extracellular lipids that ES treatment decreases macrophage number and cholesterol level, increases the collagen and smooth muscle cells in the arterial intima and media, and thus exerts effect on plaque reversing.