【摘要】 目的:探究山奈酚通过调节Notch信号通路促进大鼠骨折愈合和血管生成。方法:随机选择18只大鼠作为假手术组，其余大鼠构建骨折大鼠模型，将造模成功的骨折大鼠随机平分为模型组、山奈酚组(腹腔注射100 mg/(kg·d)山奈酚)、抑制剂组(腹腔注射5 mg/(kg·d) Notch信号通路抑制剂DAPT)、山奈酚+抑制剂组(腹腔注射100 mg/(kg·d)山奈酚和5 mg/(kg·d) DAPT),连续治疗8周，每组均18只。微型计算机断层扫描分析骨折愈合情况；ELISA法检测骨代谢指标；免疫荧光染色检测CD31表达；Western Blot法检测骨形成标志物(BMP2、SOX9)、血管生成标志物(VEGF和MMP9)以及Notch信号通路蛋白表达。结果:X射线图像表明，模型组骨折部位的桥连接较弱。显微CT重建图像进一步说明，模型组缝隙相对较宽，愈伤组织较小。模型组较假手术组骨体积/组织体积(BV/TV)、愈伤组织面积、BALP、BGP含量、CD31阳性表达率、VEGF、MMP9、Notch1、HES1、HEY1蛋白水平均显著下降，CTX-Ⅰ含量显著升高，差异有统计学意义(P<0.05);山奈酚组较模型组骨折部位的桥连接改善，缝隙相对变窄，BV/TV、愈伤组织面积、BALP、BGP、CD31阳性表达率、VEGF、MMP9、Notch1、HES1、HEY1蛋白水平显著升高，CTX-Ⅰ含量显著下降，差异有统计学意义(P<0.05),而抑制剂组与山奈酚组以上指标结果相反；DAPT恢复了山奈酚对骨折大鼠血管生成和骨折愈合的影响。结论:山奈酚可促进骨折大鼠血管生成和骨折愈合，其机制与Notch信号通路的激活相关。更多还原

【Abstract】 Objective:To explore the effects of kaempferol on fracture healing and angiogenesis in rats by regulating Notch signal pathway.Methods:Eighteen rats were randomly selected and recorded as sham operation group, and the rest rats were used to construct fracture rat model.The fracture rats that were successfully modeled were randomly divided into model group, kaempferol group(intraperitoneal injection of 100 mg/(kg·d) kaempferol),inhibitor group(intraperitoneal injection of 5 mg/(kg·d) Notch signal pathway inhibitor DAPT),and kaempferol+inhibitor group(intraperitoneal injection of 100 mg/(kg·d) kaempferol and 5 mg/(kg·d) DAPT) for 8 consecutive weeks, 18 rats in each group.The fracture healing was analyzed by computerized tomography; bone metabolism was detected by ELISA;the expression of CD31 was detected by immunofluorescence staining; and Western Blot was applied to detect the expression of bone formation markers(BMP2,SOX9),angiogenesis markers(VEGF and MMP9) and Notch signal pathway proteins.Results:X-ray images showed that the bridge connection of fracture site in model group was weak.The micro CT reconstruction images further showed that the gap in model group was relatively wide and the callus was smaller.Compared with Sham operation group, the bone volume/tissue volume(BV/TV),callus area, BALP,BGP contents, CD31 positive expression rate, VEGF,MMP9,Notch1,HES1,and HEY1 protein levels in model group decreased obviously, the CTX-Ⅰ content increased obviously(P<0.05);compared with model group, the bridge connection of fracture site in kaempferol group was improved, and the gap was relatively narrow, the BV/TV,callus area, BALP,BGP,CD31 positive expression rate, VEGF,MMP9,Notch1,HES1,HEY1 protein levels increased obviously, the CTX-Ⅰ content decreased obviously(P<0.05),the results of the above indexes in DAPT group and kaempferol group were opposite; DAPT restored the effects of kaempferol on angiogenesis and fracture healing in fracture rats.Conclusion:kaempferol can promote angiogenesis and fracture healing and angiogenesis in fracture rats, and its mechanism is related to the activation of Notch signal pathway.更多还原