洛伐他汀联合胰岛素干预双侧卵巢切除2型糖尿病SD模型大鼠骨折的愈合  

Lovastatin combined with insulin effects on fracture healing in rat models of bilateral ovariectomized type 2 diabetic mellitus

作　　者：曹国龙 田发明 刘家寅[3] Cao Guolong;Tian Faming;Liu Jiayin(Department of Orthopedics,Worker’s Hospital of Tangshan,Tangshan 063000,Hebei Province,China;Medical Experimental Research Center of North China University of Science and Technology,Tangshan 063000,Hebei Province,China;Department of Orthopedics,the Second Hospital of Tangshan,Tangshan 063000,Hebei Province,China)

机构地区：[1]唐山市工人医院骨外科,河北省唐山市063000 [2]华北理工大学医学实验研究中心,河北省唐山市063000 [3]唐山市第二医院骨外科,河北省唐山市063000

出　　处：《中国组织工程研究》2020年第5期673-681,共9页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金(81874029)，项目负责人：田发明;河北省自然科学基金(H2013209255)，项目负责人：田发明;唐山市科技计划项目(12130236b)，项目负责人：曹国龙~~

摘　　要：背景:2型糖尿病骨质疏松女性骨折患者,往往伴随血脂异常,在给予胰岛素控制血糖的同时,还常需应用他汀类药物联合治疗,但是这2种药物联合应用对于此类患者骨折愈合有何影响还未见报道。目的:探讨洛伐他汀联合胰岛素对于去卵巢2型糖尿病大鼠骨折愈合过程的影响。方法:实验方案经华北理工大学实验伦理委员会批准。雌性SD大鼠32只随机分为正常对照组、2型糖尿病并发骨质疏松骨折组、胰岛素治疗组和胰岛素联合洛伐他汀组。除正常组外,所有大鼠建立2型糖尿病并骨质疏松骨折大鼠模型,胰岛素治疗组和胰岛素联合洛伐他汀组大鼠在注射链脲佐菌素7d建立2型糖尿病模型成功后,行皮下注射胰岛素直至实验结束,胰岛素剂量为早2-4U、晚4-6U;其余2组不做处理;胰岛素联合洛伐他汀组大鼠每日给予20 mg/kg洛伐他汀灌胃。在骨折后第3周时麻醉后处死大鼠,通过对各组骨痂进行影像学、临床检测及组织形态学分析,并检测其内骨形态发生蛋白2、血管内皮生长因子和Ⅱ型胶原蛋白的表达,来分析各组大鼠骨折愈合情况。结果与结论:(1)2型糖尿病并发骨质疏松骨折组大鼠骨折愈合X射线评分、Micro-CT各项指标、组织形态学评分及血管内皮生长因子、Ⅱ型胶原蛋白的表达均较正常骨折对照组出现显著受损(P<0.05);(2)经胰岛素治疗后,胰岛素治疗组以上指标均较2型糖尿病并发骨质疏松骨折组显著改善(P <0.05),促进了模型大鼠骨折愈合;(3)但在胰岛素治疗基础上联合洛伐他汀治疗后,虽然进一步促进骨痂内血管内皮生长因子和骨形态发生蛋白2的表达(P <0.05),但是对于骨折的影像学表现和骨痂组织的微结构并无显著改善。BACKGROUND:Osteoporotic fracture combined with type 2 diabetic mellitus in female patients is often accompanied by dyslipidemia and hyperglycemia.In addition to insulin treatment,statins are often prescribed for combination therapy,but the combined effect of these two drugs on fracture healing has not been reported in such patients.OBJECTIVE:To investigate the effect of lovastatin combined with insulin on the fracture healing of bilateral ovariectomized rats suffering from type 2 diabetic mellitus.METHODS:The study was approved by the Ethical Committee of North China University of Science and Technology.Thirty-two female Sprague-Dawley rats were divided into control,diabetic ovariectomized,insulin and combined groups.A model of type 2 diabetes and osteoporosis fracture was established in all rats except for the control group.At 7 days after the type 2 diabetic model was successfully established by injection of streptozotocin,the rats in the insulin and combined groups received the subcutaneous injection of insulin(2-4 U in the morning,and 4-6 U in the evening) until the end of the experiment.The rats in the combined group were given 20 mg/kg lovastatin via gavage daily,and those in the other two groups were not treated.All rats were sacrificed at 3 weeks after fracture.Radiographic,clinical and histomorphometric detections of the callus were performed.The expression levels of bone morphogenetic protein 2,vascular endothelial growth factor and collagen type II were detected.All above results were used to analyze the fracture healing in each group.RESULTS AND CONCLUSION:(1) The radiographic score,micro-CT index,histologic score and the expression levels of vascular endothelial growth factor and collagen type II in the diabetic ovariectomized group were significantly poorer than those in the control group(P<0.05).(2) All above indexes in the insulin group were significantly improved compared with the diabetic ovariectomized group(P<0.05),which promoted the fracture healing of model rats.(3) After combined with lovas

关 键 词：2型糖尿病 骨质疏松症 雌激素缺乏 骨折 胰岛素 洛伐他汀 骨形态发生蛋白2 血管内皮生长因子 Ⅱ型胶原蛋白 

分 类 号：R446[医药卫生—诊断学] R496[医药卫生—临床医学]