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冬凌草甲素对骨质疏松大鼠骨折愈合的影响及其机制

Effect and its mechanism of oridonin on fracture healing in osteoporotic rats
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摘要 目的探讨冬凌草甲素对骨质疏松大鼠骨折愈合的影响及其机制。方法将SD大鼠随机分为对照组、模型组、冬凌草甲素低剂量组、冬凌草甲素高剂量组、戊酸雌二醇组、冬凌草甲素高剂量+环巴胺组,每组12只。X射线检测评估大鼠骨折愈合情况;ELISA法检测血清中肿瘤坏死因子-α(TNF-α)、白细胞介素6(IL-6)水平;三点弯曲实验检测股骨最大载荷和最大位移;双能X线骨密度扫描仪检测股骨骨密度;HE-阿尔新蓝染色检测骨痂组织病理变化;Western blot检测碱性磷酸酶(ALP)、Runt相关转录因子2(Runx2)、Shh、Gli1蛋白表达。结果与对照组比较,模型组骨小梁结构紊乱,骨折线清晰,血清中TNF-α和IL-6水平升高(P<0.05),股骨最大载荷、最大位移、骨密度及ALP、Runx2、Shh和Gli1蛋白表达降低(P<0.05);与模型组比较,冬凌草甲素低剂量组、冬凌草甲素高剂量组和戊酸雌二醇组骨小梁排列较密集,骨折线模糊不清,血清中TNF-α、IL-6水平降低(P<0.05),股骨最大载荷、最大位移、骨密度及ALP、Runx2、Shh、Gli1蛋白表达升高(P<0.05);与冬凌草甲素高剂量组比较,冬凌草甲素高剂量+环巴胺组骨小梁结构疏松,骨折线较清晰,血清中TNF-α和IL-6水平升高(P<0.05),股骨最大载荷、最大位移、骨密度及ALP、Runx2、Shh和Gli1蛋白表达降低(P<0.05)。结论冬凌草甲素可能通过激活声波刺猬(Shh)/Gli家族锌指蛋白1(Gli1)信号通路促进骨质疏松大鼠骨折愈合。 Objective To investigate the effect of oridonin on fracture healing in osteoporotic rats and its mechanism.Methods SD rats were randomly divided into control group,model group,low-dose oridonin group,high-dose oridonin group,estradiol valerate group,and high-dose oridonin+cyclophosphamide group,with 12 rats in each group.The fracture healing of rats was evaluated by X-ray.ELISA method was applied to detect the levels of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in serum.Three-point bending experiment was applied to detect the maximum load and the maximum displacement of the femur.Bone mineral density of femur was measured by dual-energy X-ray bone density scanner.HE-Alcianblue staining was applied to detect pathological changes of callus tissue.Western blot was applied to detect the expressions of alkaline phosphatase(ALP),Runt-related transcription factor 2(Runx2),Shh,and Gli1 proteins in callus tissue.Results Compared with control group,the bone trabecular structure of rats was disordered and the fracture line was clearly visible in model group,the levels of TNF-αand IL-6 in serum increased(P<0.05),and the maximum load,the maximum displacement,the bone density,and the expressions of ALP,Runx2,Shh,and Gli1 proteins in the femur decreased in model group(P<0.05).Compared with model group,the bone trabeculae of rats were densely arranged and the fracture line was blurred,the levels of TNF-αand IL-6 in serum decreased(P<0.05),and the maximum load,the maximum displacement,the bone density,and the expressions of ALP,Runx2,Shh,and Gli1 proteins in the femur increased in low-dose oridonin group,high-dose oridonin group,and estradiol valerate group(P<0.05).Compared with high-dose oridonin group,the bone trabeculae of rats became thinner and the fracture line was clearer,the levels of TNF-αand IL-6 in serum increased(P<0.05),and the maximum load,the maximum displacement,the bone density,and the expressions of ALP,Runx2,Shh,and Gli1 proteins in the femur decreased in high-dose oridonin A+cyclophosphamide group(P<0.05).Conclusion Oridonin may promote fracture healing in osteoporotic rats by activating the Shh/Gli1 signaling pathway.
作者 成翕悦 李丹丹 崔如 靖博雅 曹岩 赵晶 刘俊川 CHENG Xiyue;LI Dandan;CUI Ru;JING Boya;CAO Yan;ZHAO Jing;LIU Junchuan(Department of General Practice,Third Hospital of Hebei Medical University,Shijiazhuang 050051,China;First Department of Orthopedics,Friendship Branch of Third Hospital of Hebei Medical University)
出处 《山西医科大学学报》 CAS 2023年第12期1625-1631,共7页 Journal of Shanxi Medical University
基金 河北省自然科学基金资助项目(编号:H2022206383) 河北省医学科学研究课题计划项目(编号:20211107)。
关键词 冬凌草甲素 声波刺猬/Gli家族锌指蛋白1通路 骨质疏松 骨折愈合 炎症 oridonin sonic hedgehog/Gli family zinc finger protein 1 pathway osteoporosis fracture healing inflammation
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