漆黄素对去卵巢大鼠骨质疏松症的影响  

Effects of Fisetin on Osteoporosis in Rats Undergoing Ovariectomy

作　　者：杨鑫[1] 李源力 蒋萍[1] 王冶 敬雪明[2] YANG Xin;LI Yuanli;JIANG Ping;WANG Ye;JING Xuemingb(Department of Orthopedics,the Affiliated Hospital of North Sichuan Medical College,Nanchong,Sichuan 637000,China;Department of Nephrology,the Affiliated Hospital of North Sichuan Medical College,Nanchong,Sichuan 637000,China)

机构地区：[1]川北医学院附属医院骨外科,四川南充637000 [2]川北医学院附属医院肾内科,四川南充637000

出　　处：《临床误诊误治》2023年第7期38-43,共6页Clinical Misdiagnosis & Mistherapy

基　　金：四川省教育厅课题(17ZB0174)。

摘　　要：目的 探讨漆黄素对去卵巢大鼠骨质疏松症的影响。方法 将50只雌性SD大鼠采取双侧卵巢切除法构建骨质疏松症模型,分为模型组、漆黄素10、20、40 mg/kg组及阳性对照组,每组10只。漆黄素组给予不同浓度漆黄素干预,阳性对照组给予雌二醇(E_(2))干预,连续8周。另选10只大鼠作为假手术组。检测各组大鼠血清碱性磷酸酶(ALP)、骨钙素(OCN)、E_(2)、Ⅰ型胶原羧基C端交联肽(CTX-Ⅰ)、骨γ-羧基谷氨酸蛋白(BGP)以及骨密度(BMD),HE染色观察骨组织形态学,采用Micro-CT测定骨指标[骨体积分数(BV/TV)、骨小梁厚度(Tb.Th)、骨小梁分离度(Tb.Sp)、骨小梁数目(Tb.N)],采用生物力学材料实验机检测骨生物力学参数(股骨颈加载力、胫骨轴强度、腰椎压缩力),Western-blot检测Runt相关转录因子2(Runx2)、低密度脂蛋白受体相关蛋白-5(Lrp-5)、β-联蛋白(β-catenin)和成骨细胞特异性转录因子Osterix(Osx)表达水平。结果 与假手术组比较,模型组ALP、OCN、Tb.Sp、CTX-Ⅰ显著升高,E_(2)、BMD、BV/TV、Tb.Th、Tb.N、BGP、股骨颈加载力、胫骨轴强度、腰椎压缩力、Runx2、Lrp-5、β-catenin、Osx水平显著降低(P<0.05);HE染色显示股骨骨小梁排列疏松、网状结构破坏、小梁数减少且断裂点增多。与模型组比较,漆黄素40 mg/kg组及阳性对照组ALP、OCN、Tb.Sp、CTX-Ⅰ显著降低,E_(2)、BMD、BV/TV、Tb.Th、Tb.N、BGP、股骨颈加载力、胫骨轴强度、腰椎压缩力、Runx2、Lrp-5、β-catenin、Osx水平显著升高(P<0.05);HE染色显示股骨骨小梁排列及网状结构明显恢复,有较高的骨连接。结论 漆黄素可提高去势骨质疏松大鼠骨应力,其作用机制可能与促进Wnt/β-catenin蛋白通路、降低大鼠体内高骨转换速率有关。Objective To investigate the effects of Fisetin on osteoporosis in rats undergoing ovariectomy.Methods A total of 50 female SD rats were treated with bilateral ovariectomy to construct a model of osteoporosis,and divided into model group,Fisetin 10 mg/kg group,Fisetin 20 mg/kg group,Fisetin 40 mg/kg group and positive control group,with 10 rats in each group.Fisetin group was given different concentrations of Fisetin intervention,and the positive control group was given estradiol(E_(2)) for 8 consecutive weeks.Another 10 rats were selected as sham operation group.Serum alkaline phosphatase(ALP),osteocalcin(OCN),E_(2),carboxyl C-terminal cross-linked peptide of type Ⅰ collagen(CTX-Ⅰ),bone γ-carboxyl glutamate protein(BGP) and bone mineral density(BMD) were detected in each group.Bone morphology was observed by HE staining.Bone indexes [bone volume fraction(BV/TV),trabecular thickness(Tb.Th),trabecular separation(Tb.Sp),trabecular number(Tb.N)] were detected by micro-CT,and bone biomechanical parameters(femoral neck loading force,strength of tibial axis,lumbar compression force) were detected by Micro-CT.The expression levels of Runt-associated transcription factor 2(Runx2),low-density lipoprotein receptor-associated protein-5(Lrp-5),β-catenin and osteoblast-specific transcription factor Osterix(Osx) were detected by Western blot.Results Compared with sham operation group,ALP,OCN,Tb.Sp and CTX-Ⅰ in model group were significantly increased.The levels of E_(2),BMD,BV/TV,Tb.Th,Tb.N,BGP,femoral neck loading force,strength of tibial axis,lumbar compression force,Runx2,Lrp-5,β-catenin and Osx were significantly decreased(P<0.05).HE staining showed loose arrangement of trabeculae,destruction of reticular structure,reduction of trabecular number and increase of fracture points.Compared with model group,ALP,OCN,Tb.Sp and CTX-Ⅰ in Fisetin 40 mg/kg group and positive control group were significantly decreased.The levels of E_(2),BMD,BV/TV,Tb.Th,Tb.N,BGP,femoral neck loading force,strength of tibial axis,lumbar comp

关 键 词：骨质疏松 绝经后 漆黄素 骨钙素 骨密度 骨体积分数 股骨颈加载力 成骨细胞特异性转录因子 大鼠 Sprague-Dawley 

分 类 号：R965.2[医药卫生—药理学]