三种联合用药方案对大鼠动脉粥样硬化及脂肪的影响

Effects of three different treatments on atherosclerosis and adipose in rats

目的研究普罗布考联合阿司匹林（PS）、洛伐他汀联合阿司匹林（AS）以及普罗布考、洛伐他汀联合阿司匹林（PAS）3种不同联合用药方案对动脉粥样硬化大鼠斑块稳定及脂肪的影响。方法将完成动脉粥样硬化造模的SD大鼠按随机数字表法分为对照组（n=7）、高脂组（n=4）、PS组（n=8）、AS组（n=5）、PAS组（n=7）5组。PS组采用普罗布考（104．4mg／kg）联合阿司匹林（10．4mg·kg^-1·d^-1）灌胃、AS组采用阿司匹林（10．4mg·kg^-1·d^-1）联合洛伐他汀（2．1mg·kg^-1·d^-1）、PAS组给予普罗布考（104．4mg·kg^-1·d^-1）、阿司匹林（10．4mg·kg^-1·d^-1）和洛伐他汀（2．1mg·kg^-1·d^-1）灌胃8周治疗。同时对照组给予等体积生理盐水灌胃。通过体质量及不同部位脂肪称重、血清生化指标、病理变化综合评价联合用药对动脉粥样硬化斑块稳定及脂肪的影响。结果灌胃治疗2周后，PS组（251g±5g）、PAS组（247g±7g）体质量明显高于高脂组（220g±6g，P〈0．01）。AS组（440g±9g）灌胃3周体质量明显高于高脂组（197g±6g）（P〈0．05）；治疗8周后，PS组、AS组、PAS组心脏、肾脏、肾脏周围脂肪、胃肠道周围脂肪的绝对质量和相对质量明显高于高脂组（P〈0．01）；血清总胆固醇，PS组（1．67mmol／L±0．12mmol／L）、PAS组（1．77mmol／L±0．15mmol／L）、AS组（1．80mmol／L±0．16mmol／L）明显低于高脂组（28．45mmol／L±3．07mmol／L，P〈0．01）；炎症因子PAS组血清炎症因子TNF—α（27pg／ml±21pg／m1）明显低于高脂组（100pg／ml±34pg／ml，P〈0．05）；病理切片（主动脉血管条油红染色、不同脏器冰冻切片油红染色及不同部位主动脉HE染色）动脉粥样硬化斑块稳定方面明显优于AS组。结论PS组、AS组、PAS组均有不同程度改善大鼠动脉粥样硬化的作用，其中以PS组、PAS组疗效最佳。由脂肪相关指标变化推测，脂肪因子可能在其中发挥了重要作用。

Objective To explore the effects of three different treatments, including probucol plus aspirin （PS）, lovastatin plus aspirin （AS） and probucol, lovastatin plus aspirin （PAS） on atherosclerotic plaque and adipose. Methods A total of 31 SD rats with established atherosclerosis were randomly divided into control group （ n = 7）, high-fat group （ n = 4）, PS group （ n = 8 ）, AS group （ n = 5 ） and PAS group （n =7）. The PS group rats were lavaged with probucol （104.4 mg·kg^-1·d^-1） and aspirin 10. 4 mg·kg^-1·d^-1） , AS group ones aspirin （10.4 mg·kg^-1·d^-1 ） and lovastatin （2. 1 mg·kg^-1·d^-1 ） and PAS group ones probucol （ 104. 4 mg·kg^-1·d^-1 ）, aspirin （ 10.4mg·kg^-1·d^-1 ） and lovastatin （2. 1mg·kg^-1·d^-1 ） for 8 weeks. At the same time, the control group received an equal volume of saline. Finally the plaque stability and adipose function of treatment groups were evaluated by the changes of body weight, serum parameters, adipose weights and pathological specimens. Results Body weights in PS and PAS groups significantly increased than those in AS group （251 g ± 5 g and 247 g ± 7 g vs 220 g ± 6 g, P 〈0. 01 ）. The serum levels of low density lipoprotein cholesterol （LDL）, glucose （Glu）, total cholesterol （TC） and high density lipoprotein cholesterol （HDL） were significantly better in PS and PAS groups than those in AS group （P 〈 0. 01 ）. The level of tumor necrosis factor-alpha （TNF-a） was lower in PAS groupthan that in high-fat group （27 ±21 vs 100 ± 34 pg/ml, P 〈 0. 05）. The stability level of atherosclerotic plaque was more in PAS group than those in PS and AS groups by oil red staining in aorta, oil red staining in different organs and hematoxylin and eosin staining in different aortal parts. Conclusion Atherosclerosis improves more pronouncedly in PS and PAS groups than that in AS group. Through an analysis of the changes of fat-related indicators, adipose factor may play an important role in atherosclerotic treatment.