瑞舒伐他汀钙对家兔腹主动脉球囊损伤后内膜增生及转化生长因子β1表达的影响

摘要

Objective To evaluate the effect of rosuvastatin on intimal hyperplasia in abdominal aorta and expression of TGF-β1 after balloon injury of aorta in rabbits. Methods Twenty male New Zealand rabbits were used to reproduce the model of injured abdominal aorta with balloon, and then they were divided randomly into two groups (10 each): rosuvastatin group and control group. Rabbits in control group were given aspirin 25rng/d and clopidogrel 25mg/d, while in rosuvastatin group the rabbits received additional rosuvastatin at a dose of 1mg/(kg· d). Abdominal aorta angiography and blood biochemical examination were done 6 weeks after administration of the durgs,and the vascular wall specimens were obtained from the injured aorta. They were studied under microscope with HE staining, and the proliferation of aortic intima and the expression of TGF-β1 were then analyzed. Results The abdominal aorta angiography showed that the diameters of aorta at the narrowest part was 32％ larger in rosuvastatin group (1. 74±0. 25mm) than in control group (1.32±0. 33mm),and the extent of stenosis was decreased by 43％ in rosuvastatin group (31.41％±7. 08％) than in control group (55. 25％±10. 23％).HE staining showed the thickness of intima decreased by 50％ in rosuvastatin group (0. 04±0. 02mm) than in control group (0. 08±0. 03mm), and the lumen area in rosuvastatin group (3. 9±0. 03mm2 ) was 1. 63 times larger than that in control group (2. 4±0. 02mm2 ).The average absororence rate and the area of positive TGF-β1 were significantly lower in rosuvastatin group than in control group (0. 413±0.13 vs 0. 568± 0.17; 22. 37％ ± 4. 42％ vs 40.58％±7.45％, respectively, P＜0.05). Conclusion Rosuvastatin may inhibit the ncointimal hyperplasia after balloon injury of the abdominal aorta in rabbits through down regulating the expression of TGF-β1.%目的 观察瑞舒伐他汀钙对家兔腹主动脉球囊损伤内膜增生及转化生长因子β1(TGF-β1)表达的影响,并探讨其在防治支架术后再狭窄中的可能性及机制.方法 雄性新西兰兔20只,制作腹主动脉球囊损伤模型后随机分成他汀组与对照组(n=10).两组均予阿司匹林25mg/d、氯吡格雷25mg/d,他汀组加用瑞舒伐他汀钙1mg/(kg·d),连续灌胃给药6周后,进行血生化检测及腹主动脉造影,截取球囊损伤处血管组织行HE染色,光镜下观察内膜增生情况,免疫组化检测TGF-β1表达情况.结果 腹主动脉造影显示,他汀组血管狭窄段最小内径(1.74±0.25mm)较对照组(1.32±0.33mm)增加32%,狭窄程度(31.41%±7.08%)较对照组(55.2%±10.23%)减轻43%.HE染色显示,他汀组内膜厚度(0.04±0.02mm)较对照组(0.08±0.03mm)减少50%,管腔面积(3.9±0.03mm2)较对照组(2.4±0.02mm2)增加62.5%.免疫组化结果显示,他汀组TGF-β1平均吸光度、阳性面积率(分别为0.41±0.13、22.37%±4.42%)明显低于对照组(分别为0.57±0.17、40.58%±7.45%),差异有统计学意义(P<0.05).结论 瑞舒伐他汀钙可抑制腹主动脉球囊损伤后家兔的内膜增殖,其机制可能与降低TGF-β1表达有关.