摘要
目的 探讨重组人成纤维细胞生长因子 -2 (recombinanthumanFibroblasticGrowthFactor -2 ,rhFGF -2 )和可溶性肿瘤坏死因子I型受体蛋白 (solubleTumorNecrosisFactorReceptor -1,sTNF -R1)联合治疗Ⅱ型糖尿病引起的骨再生与修复障碍的作用。 方法 雄性Zucker糖尿病大鼠 (ZuckerDiabeticfattyrat ,ZDF/Gmi-fa/fa) 2 0只 ,随机分为对照组 (n =10 )和治疗组 (n =10 )。检测体重 ,血糖、尿糖和尿酮。一周后 ,所有大鼠接受左胫骨中上段低能截骨 ,安置外延长固定架。第二天起开始每天胫骨延长 ,速率为 0 .2mmB .i .d .,共 14d。期间 ,治疗组大鼠接受截骨处血肿内rhFGF-2 ( 2 5 μg/2 5 μl)注射一次 ,sTNF -R1( 8mg/kg)皮下注射每二日一次 ,共 14d。对照组仅接受载体和生理盐水注射。然后 ,采集标本 ,分别测定血液生化指标 ,胫骨延长间隙中新生骨量及增殖细胞数量。 结果 两组大鼠血糖浓度无明显差异。治疗组大鼠的胫骨延长间隙中新生骨密度和面积均显著高于对照组大鼠。免疫组化分析显示间隙中增殖细胞数量明显增高。两组大鼠血清胰岛素及骨钙素浓度无明显差异。 结论 Ⅱ型糖尿病可引起骨再生与修复障碍 ,rhFGF -2和sTNF -R1联合治疗可促进成骨细胞增殖 ,加快牵引成骨速率 ,实验结果提示这两种药物的?
Objective This work was conducted to investigate the effect of recombinant human Fibroblastic Growth Factor-2 (rhFGF-2) combined with soluble Tumor Necrosis Factor Receptor-1 (sTNF-R1) on impaired bone regeneration and repair using Zucker Diabetic fatty (ZDF) rat, a model of type II diabetes mellitus. Methods Twenty male ZDF rats (ZDF/Gmi-fa/fa) were designed into treated (n=10) and control (n=10) groups. All rats were examined for body weight, glycosuria, and glycosemia to confirm the diabetic condition during the study. The rats received placement of the external fixators and osteotomies on the left tibia. Distraction was initiated the following day at 0.2 mm b.i.d. and continued for 14 days. Treated rats received an injection of rhFGF-2 (25 μg/25 μl) into the hematoma of the osteotomic gap, while control rats received an injection of vehicle (25 μl/gap). sTNF-R1 (8 mg/kg) or the same amount of saline was subcutaneously injected into treated and control rats, respectively every two days for 14 days. The lengthened tibiae and blood sample were harvested. The serum and distraction gaps were biochemically and histologically analyzed. Results There was no significant difference in blood glycose between two groups. The results showed a significant increase in the density and area of newly formed bone in the distraction gaps of treated rats compared to control rats. An increased cell proliferation was also found in the distraction gaps of treated rats versus control rats. There was no significant difference in serum levels of insulin and osteocalcin between two groups. Conclusion The results suggest that local application of rhFGF-2 combined with systemic sTNF-R1 can enhance bone formation by increasing proliferation during distraction osteogenesis in ZDF rats. The combination of rhFGF-2 and sTNF-R1 may be an effective treatment for type II diabetic patients with fracture healing problem.
出处
《实用预防医学》
CAS
2004年第3期464-467,共4页
Practical Preventive Medicine
