骨髓间充质干细胞促进糖尿病大鼠骨折愈合的研究

Effect of bone marrow mesenchymal stem cells on fracture healing in diabetic rats

目的检测促炎因子TNF-α、IL-6及抗炎因子IL-4、IL-10以及Toll样受体4在骨髓间充质干细胞促进糖尿病大鼠骨折愈合过程中的动态变化,探讨炎症失衡在此过程中的作用及可能机制。方法 7~8周龄SPF级雄性自发性2型糖尿病GK大鼠56只,喂养高脂饲料造模。造模成功后(随机血糖≥11.1 mmol/L)暴露大鼠左侧股骨,人为造成开放性骨折并给与克氏针复位内固定,将培养收集浓缩的骨髓间充质干细胞注射于骨折周围肌肉软组织,于实验后第1周、3周、6周、8周分别行X线摄片、下腔静脉取血测定炎症因子、骨折局部软组织检测TLR4表达。结果术后第1周、3周、6周、8周对照组TNF-a、IL-6、TLR-4表达均高于实验组(P<0.05),而IL-4、IL-10则低于实验组(P<0.05);两组动物在手术后第三周均可见骨折处骨痂生长,实验组更加明显,但对照组骨痂不均匀,骨密度较低。结论骨髓间充质干细胞局部移植可以降低GK糖尿病大鼠骨折后机体的炎症反应,促进骨折愈合。

Objective To study the role of inflammation imbalance on mesenchymal stem cells promoting fracture healing in a model of GK diabetic rats by detecting the dynamic changes of the level ofinflammation factors TNF?α,IL?6,IL?4,IL?10and the expression of Toll?like receptor?4(TLR?4).Methods The diabetic model on GK rats was induced by feeding high?fat diet(random blood sugar≥11.1mmol/L).The fracture was fixed with kirschner wire after the left thigh?bone of rats were exploded and sawed off,and then the concentrated stem cells were injected into the local area of the fracture.We collected the blood and tissue specimen to detect the concentrations of TNF?α,IL?6,IL?4,IL?10and the expression of TLR?4in one week,three week,six week and eight week after fracture fixation.The fracture healing was evaluated by X?ray.Results The levels of TNF?α,IL?6and the expression of TLR?4were higher in the control group than those in the experimental group(all P values<0.05),however,the levels of IL?4and IL?10were lower in the control group(all P values<0.05).The osteotylus formation was more obvious and the bone mineral density was more homogeneous in the experimental group.Conclusion In the present study,our findings demonstrated that the local transplantation of bone marrow mesenchymal stem cells reduced the inflammatory response and promote fracture healing fracture in diabetic GK rats.