柚皮苷对去势大鼠骨折骨痂血管发生的影响及其机制  

The effect and mechanism of naringin on callus angiogenesis of ovariectomized rats＇ fractures

作　　者：赵志虎[1,2] 孟新民[1] 孙晓雷[1] 马剑雄[1] 李风波[1] 李艳军[1] 吕建伟[2] 马信龙[1] 

机构地区：[1]天津医院骨科研究所,300211 [2]天津医科大学研究生院,300052

出　　处：《中华骨科杂志》2016年第3期177-183,共7页Chinese Journal of Orthopaedics

基　　金：天津市中医药管理局重点资助项目（13123）;国家自然科学基金青年基金（81401792,81501061）

摘　　要：目的探讨柚皮苷（naringin）对去势大鼠早期骨折愈合中血管形成（angiogenesis ＆ neovascularization）的影响及其机制。方法建立去势大鼠胫骨中上1/3骨折模型并随机分为柚皮苷组（300mg／kg）和对照组。在骨折后2周，进行Microfil灌注，灌注后行Micro-CT扫描，利用HE染色技术从组织学方面评价组织血管化程度，提取骨痂处总RNA，运用Real—time PCR技术定量分析血管内皮生长因子（vessel endothelial growth factor, VEGF）的表达量。同时对骨痂处组织行血管内皮生长因子受体-2（vessel endothelial growth factor receptor-2, VEGFR-2）免疫组织化学染色，三点弯曲力学试验测量骨痂处最大载荷。结果柚皮苷组较对照组的血管体积更大，血管数量更多，血管更密集。组织学切片HE染色结果显示，柚皮苷组相比对照组骨痂单位高倍视野下的血管数量和血管面积增高，差异有统计学意义；RT—PCR结果显示，柚皮苷组与对照组比较可以明显促进VEGF的表达，差异有统计学意义。柚皮苷组骨痂处VEGFR-2阳性细胞数明显高于对照组，差异有统计学意义。柚皮苷组可以明显提高骨痂最大载荷，差异有统计学意义。结论柚皮苷可以促进去势大鼠骨折早期愈合过程中的血管形成并增强骨折愈合强度，这可能是通过调节VEGF／VEGFR-2信号通路实现。Objective To explore the angiogenesis ＆ neovascularization effects of naringin treatment in ovariectomized rats＇ fracture healing. Methods Upper 1/3 transverse tibial fracture model 4 weeks later after ovariectomized were estimated and randomly divided into the naringin group and control group. Microfil perfusion technique was used to analysis the angiogenesis situation at two weeks after bone fracture. HE staining was used to evaluate the level of angiogenesis ＆ neovascularization of tissue from histological point of view. The relative expression of VEGF in the callus was identified by real-time polymerase chain reaction. Immunohistochemical technique was used to observe the vessel endothelial growth factor-2 in the callus of the two groups. Maximum fracture load was tested by three-point bend test. Results The vascular volume and vascular density were more in naringin group than control group. The HE staining of the 2 week group slices shows that the VA, VN2 of the unit of high magnification vision of the naringin group was significantly larger compared to the control group. Real-time PCR revealed that the comparative expression of VEGF is more in naringin group than in control group; the positive number of VEGFR- 2 is more in naringin group than in control group. Naringin can promote the maximum load of the callus. Condusion Naringin can promote ovariectomized rats＇ angiogenesis ＆ neovascularization in the early process of fracture healing. It may be act on the signaling pathway of VEGF/VEGFR-2.

关 键 词：骨碎补 骨折愈合 新生血管化 生理性 大鼠 卵巢切除术 

分 类 号：R683[医药卫生—骨科学]