基于VEGF/VEGFR-2信号通路探讨穿山龙总皂苷促进去势大鼠骨折血管形成和骨折愈合的效果  

Effect of Total Saponins of Dioscorea Paniculata on Fracture Angiogenesis and Fracture Healing in Ovariectomized Rats Based on VEGF/VEGFR-2 Signaling Pathway

作　　者：安晓晖[1] 刘恩[1] 吕飞[1] 冯志伟[1] An Xiaohui;Liu En;LV Fei;Feng Zhiwei(Jizhong Energy Fengfeng Group Hospital,Hebei,Handan 056200,China)

机构地区：[1]冀中能源峰峰集团总医院,河北邯郸056200

出　　处：《中国中医急症》2020年第5期846-849,869,共5页Journal of Emergency in Traditional Chinese Medicine

基　　金：河北省医学科学研究重点课题计划项目(20181713)。

摘　　要：目的基于血管内皮生长因子(VEGF)/血管内皮生长因子受体-2(VEGFR-2)信号通路观察穿山龙总皂苷促进去势大鼠骨折血管形成和骨折愈合的效果。方法 SD雌性大鼠50只,根据体质量随机分为骨折对照组、模型组、地塞米松组(10 mg/kg)、穿山龙总皂苷低剂量组(20 mg/kg)和穿山龙总皂苷高剂量组(40 mg/kg)。模型组、地塞米松组、穿山龙总皂苷低剂量组、穿山龙总皂苷高剂量组经戊巴比妥钠(0.3 m L/100 g)腹腔注射麻醉,切除双侧卵巢,建立去势骨折模型,骨折对照组只建立股骨的简单横向闭合性骨折。建模成功后,地塞米松组、穿山龙总皂苷低剂量组、穿山龙总皂苷高剂量组给予相应药物灌胃,模型组、骨折对照组给予等体积的0.9%氯化钠注射液。实验结束后,制作股骨折后骨痂处骨结构病理切片,对股骨折后骨痂处行骨密度、血管数量测定,RT-PCR、Western blotting法对股骨折后骨痂处VEGF、VEGFR-2基因和蛋白水平测定。结果与骨折对照组比较,模型组骨痂处骨密度、血管数量、VEGF、VEGFR-2 mRNA和蛋白表达水平明显降低(P <0.05);与模型组比较,地塞米松组、穿山龙总皂苷低剂量组、穿山龙总皂苷高剂量组骨痂处骨密度、血管数量、VEGF、VEGFR-2 mRNA和蛋白表达水平明显升高(P <0.05),且穿山龙总皂苷高剂量组骨痂处骨密度、血管数量、VEGF、VEGFR-2 mRNA和蛋白表达水平高于穿山龙总皂苷低剂量组(P <0.05);与地塞米松组比较,穿山龙总皂苷低剂量组骨痂处骨密度、血管数量、VEGF、VEGFR-2 mRNA和蛋白表达水平明显降低(P <0.05),穿山龙总皂苷高剂量组骨痂处骨密度、血管数量、VEGF、VEGFR-2 mRNA和蛋白表达水平无明显变化(P>0.05)。结论穿山龙总皂苷可促进去势大鼠骨折血管形成和骨折愈合;其机制与穿山龙总皂苷可促进去势大鼠骨折骨痂处VEGF、VEGFR-2 mRNA和蛋白表达水平,进而激活VEGF/VEGFR-2信号通路有关Objective:To investigate the effect of total saponins of Dioscorea paniculata on fracture angiogenesis and fracture healing in ovariectomized rats based on VEGF/VEGFR-2 signaling pathway. Methods:50 female SD rats were randomly divided into the control group,the model group,Dexamethasone group(10 mg/kg),low-dose total saponins of Dioscorea paniculata group(10 mg/kg)and high-dose group(40 mg/kg). The model group,Dexamethasone group,total saponins of Dioscorea paniculata low-dose group and high-dose group were anesthetized by intraperitoneal injection of pentobarbital sodium(0.3 m L/100 g);bilateral ovaries were removed and ovariectomized fracture model was established. After successful modeling,the 3 treatment groups were given corresponding drugs by gavage. The model group and the control group were given the same volume of normal saline. At the end of the experiment,histopathological sections of the callus were made;bone mineral density and blood vessel quantity were measured,and the levels of VEGF,VEGF-2 mRNA and protein were determined by RT-PCR and Western blotting. Results:Compared with the control group,the bone mineral density,vascular number,VEGF,VEGFR-2 mRNA and protein expression levels in the model group were significantly lower(P < 0.05).Compared with the model group,those in the treatment groups increased,and those in the high-dose group were significantly higher than those in the low-dose group(P < 0.05). Compared with Dexamethasone group,those indi-cators were significantly decreased(P < 0.05). There was no significant change in the high-dose group(P > 0.05).Conclusion:Total saponins of Dioscorea paniculata can promote fracture angiogenesis and fracture healing inovariectomized rats. The mechanism is related to its promoting the expression of VEGF and VEGFR-2 mRNA infracture callus of ovariectomized rats,and then activating the signal pathway of VEGF/VEGFR-2.

关 键 词：骨折 VEGF VEGFR-2 穿山龙总皂苷 去势大鼠 

分 类 号：R285.5[医药卫生—中药学]