摘要目的 探讨替米沙坦对小鼠股骨干骨折愈合的影响. 方法 取64只3个月龄雄性BALB/c小鼠,随机分为2组(n=32):实验组小鼠每天饮水中按30 mg/kg加入替米沙坦,对照组给予正常饮水.采用股骨截骨方法建立右股骨干骨折模型,于术后2、5、10周通过X线片、生物力学测试、组织形态学分析比较两组小鼠的骨折愈合情况,通过免疫组织化学方法比较两组小鼠增殖细胞核抗原及血管内皮细胞生长因子阳性表达的差异. 结果 术后2周X线片示实验组小鼠骨痂直径与股骨直径比值(243.7％±38.1％)显著大于对照组(178.2％±24.5％),差异有统计学意义(P＜0.05);术后5、10周,两组小鼠骨痂直径与股骨直径比值比较差异均无统计学意义(P＞0.05).组织形态学结果进一步支持影像学结果,与对照组比较,实验组小鼠骨形成更加显著.术后2周,实验组小鼠股骨的最大抗扭转力(31.4％±5.1％)和扭转刚度(37.7％±8.6％)均显著大于对照组(16.7％±4.2％、19.5％±7.3％),差异有统计学意义(P＜0.05).术后2周,实验组小鼠增殖细胞核抗原阳性表达(53.8％±7.5％)、血管内皮细胞生长因子阳性表达(39.2％±6.8％)均显著高于对照组(36.1％±5.4％、21.3％±4.9％),差异有统计学意义(P＜0.05). 结论 替米沙坦可能通过诱导细胞增殖和新生血管形成来促进小鼠股骨干骨折愈合.

abstractsObjective To study the effect of telmisartan on healing of femoral shaft fracture in mice.Methods Models of fracture of right femoral shaft were created by femoral osteotomy in 64 mature male BALB/c mice which were randomized into 2 equal groups (n =32).The experimental group was treated with telmisartan (30 mg/kg in drinking water) while the control group only with normal drinking water.Fracture healing was analyzed after 2,5 and 10 weeks postoperatively using X-ray,biomechanical testing,and histomorphometry.Immunohistochemistry was applied to compare the expression of proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF) in the callus between the 2 groups.Results Radiological analysis at 2 weeks postoperation showed the callus diameter in the telmisartan treated animals (243.7 ± 38.1％) was significantly larger than in the vehicle treated controls (178.2 ± 24.5％) (P ＜ 0.05).There were no significant differences in the callus diameter between the 2 groups at 5 or 10 weeks postoperation (P ＞ 0.05).Histomorphometric analyses revealed a significantly increased amount of bone formation in the experimental group compared with the control group.Biomechanical testing further showed significantly greater peak torque at failure (31.4 ± 5.1％) and significantly higher torsional stiffness (37.7 ± 8.6％) in the telmisartan-treated group than those (16.7 ±4.2％ and 19.5 ±7.3％,respectively) in the vehicle-treated group after 2 weeks of fracture healing (P ＞ 0.05).There was an increased fraction of PCNA-positive cells (53.8 ±7.5％) and VEGF-positive cells (39.2 ±6.8％) in the telmisartan-treated group compared with the vehicle-treated group (36.1 ± 5.4％ and 21.3 ± 4.9％,respectively) after 2weeks of fracture healing (P ＞0.05).Conclusions Telmisartan can promote healing of femoral shaft fracture,probably by increasing cell proliferation and neovascularization associated with decreased VEGF expression in hypertrophic chondrocytes.