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目的 探讨阿司匹林对大鼠绝经后骨质疏松的治疗作用及其相关机制.方法 将40只3月龄SD雌性大鼠随机分为5组:对照组(Sham)、去势组(OVX)及3个阿司匹林治疗组(Aspirin),每组8只.OVX及Aspirin组采用卵巢切除法去势,饲养3个月建立骨质疏松模型.确认模型建立成功后予灌胃治疗,阿司匹林治疗组剂量分别为8.93、26.79、80.36 mg/kg(A1、A2及A3),每天灌胃1次.OVX及Sham组每天予等量生理盐水灌胃.术前、术后3个月及灌胃3个月时用双能X线吸收骨密度测量仪(DXA)测量腰椎骨密度;灌胃3个月时测量外围血碱性磷酸酶及骨钙素,采用Micro-CT对骨小梁微观三维形态结构进行分析,组织病理学对骨小梁微观结构进行观察,用生物力学实验评估椎体及股骨干的力学强度.结果 DXA分析显示:去势3个月后,大鼠骨密度较术前及对照组明显降低,骨质疏松模型成功建立.灌胃治疗3个月后,阿司匹林治疗组椎体的BMD明显高于OVX组.外围血检测显示:阿司匹林治疗组的碱性磷酸酶明显低于OVX组,而骨钙素与OVX组无明显差别.组织形态学结果显示,阿司匹林治疗组骨小梁的连接、粗细较OVX组好.Micro-CT分析表明:阿司匹林治疗组腰椎椎体骨小梁厚度、骨小梁数量及骨密度率均显著高于OVX组,并且A3组与Sham组相近.生物力学结果示,阿司匹林治疗组腰椎压缩载荷及股骨干三点弯曲载荷均明显高于OVX组.结论 阿司匹林能促进大鼠绝经后骨质疏松骨小梁的改建,改善骨小梁的三维结构,增加骨质的骨密度和力学强度,有可能成为治疗骨质疏松的新型药物之一.

Objective To explore the therapeutic effects of aspirin on postmenopausal osteoporosis and understand its action mechanism. Methods Forty three-month-old female SD rats were randomly divided into 5 groups ( n = 8 each): sham group, OVX group and aspirin groups ( A1, A2 & A3 ). The OVX and aspirin groups were ovariectomized (OVX). All rats underwent BMD (bone mineral density) scan at the time of OVX and 3 months after OVX. After the animal model of osteoporosis was established, aspirin groups were intragastrically administered at a dose of 8.93 mg· kg-1 · d-1 (A1), 26. 79 mg · kg-1 · d-1(A2) and 80.36 mg · kg-1 · d-1 (A3) daily in OVX rats. Three months later, the BMD and microarchitecture of vertebrae were measured by dual-energy X-ray absorptiometry and microtomograph. Alkaline phosphatase and osteocalcin were measured in peripheral blood. The trabecular architecture changes were observed by histomorphology. Axial compression tests were used to evaluate the mechanical properties of vertebral specimens and three-point bending tests used for femur shaft. Results Three months after ovariectomy, BMD was significantly lower than preoperative. BMD in aspirin treated groups was significantly higher than that in OVX group. Alkaline phosphatase in peripheral blood decreased significantly in aspirin groups than those in OVX, but osteocalcin had no significant difference between aspirin and OVX groups.The microtomograph reconstruction analysis also showed that the trabecular thickness, trabecular number and BMD increased significantly in aspirin groups than those in OVX. And there was no significant difference between A3 and sham groups. The results of biomechanical test showed that the maximum compression load of lumbar spine and three-point bending load of femur shaft were significantly higher in aspirin groups than those in OVX group. Conclusion Aspirin can promote trabecular bone remodeling, improve threedimensional structure of trabecular bone and increase bone density of cancellous in osteoporotic rats by stimulating bone formation. It may become a new drug for the treatment of osteoporosis.