五味子甲素对去卵巢骨质疏松大鼠SDF-1/CXCR4信号通路的影响  

The Effects of Schisandra chinensis A on SDF-1/CXCR4 signaling pathway in ovariectomized osteoporosis rats

作　　者：朴海旺 金宝城[1] 赵胜军[1] PU Haiwang;JIN Baocheng;ZHAO Shengjun(Department of the Second Orthopedics,Chengde Central Hospital,Chengde 067000,China)

机构地区：[1]承德市中心医院骨二科,河北承德067000

出　　处：《中国骨质疏松杂志》2023年第9期1292-1297,共6页Chinese Journal of Osteoporosis

基　　金：河北省医学科学研究课题计划项目(编号20211635)。

摘　　要：目的探究五味子甲素对去卵巢骨质疏松症大鼠的治疗作用以及对基质细胞衍生因子-1(SDF-1)/CXC趋化因子受体4(CXCR4)信号通路的影响。方法采用去卵巢法构建骨质疏松症大鼠模型,将建模成功的60只大鼠随机分为模型组、五味子甲素低(20 mg/kg)、高(40 mg/kg)剂量组、阿仑膦酸钠(1 mg/kg)组、五味子甲素高剂量+SDF-1/CXCR4通路抑制剂(AMD3100)(40 mg/kg+5 mg/kg)组,每组12只。另取12只大鼠作为假手术组(手术过程中仅暴露卵巢不切除)。建模结束后,各组给予对应药物干预,每天1次,连续12周。采用双能X射线骨密度仪检测大鼠左、右股骨骨密度(BMD);酶联免疫吸附法检测大鼠血清中Ⅰ型胶原交联羧基末端肽(CTX-Ⅰ)、骨钙素(OC)水平;HE染色观察大鼠股骨组织病理学变化;荧光定量PCR法检测大鼠股骨组织中SDF-1、CXCR4信使RNA(mRNA)水平;蛋白印迹法检测大鼠股骨组织中SDF-1、CXCR4蛋白水平。结果假手术组大鼠股骨组织骨小梁结构正常,排列规则;与假手术组相比,模型组大鼠股骨组织骨小梁稀疏断裂,数量减少,排列紊乱,左、右股骨BMD、血清中OC、CTX-Ⅰ水平、股骨组织中SDF-1、CXCR4 mRNA和蛋白水平显著降低(P<0.05);与模型组相比,五味子甲素低、高剂量组大鼠股骨组织病变程度依次减轻,左、右股骨BMD、血清中OC、CTX-Ⅰ水平、股骨组织中SDF-1、CXCR4 mRNA和蛋白水平依次升高(P<0.05);阿仑膦酸钠组和五味子甲素高剂量组大鼠股骨组织病理学变化及各项指标差异比较均无统计学意义(P>0.05);AMD3100可逆转高剂量五味子甲素对骨质疏松症大鼠上述指标的改善效果(P<0.05)。结论五味子甲素可抑制骨质疏松症大鼠BMD的下降,减轻大鼠股骨组织病变,改善大鼠骨质疏松,其机制可能与激活SDF-1/CXCR4信号通路有关。Objective To investigate the therapeutic effect of deoxyschizandrin on ovariectomized osteoporosis rats and its effect on stromal cell derived factor-1(SDF-1)/CXC chemokine receptor 4(CXCR4)signaling pathway.Methods A rat model of osteoporosis was established by ovariectomy.Sixty rats were randomly divided into model group,deoxyschizandrin low dose(20 mg/kg)and high dose(40 mg/kg)group,alendronate sodium(1 mg/kg)group,and deoxyschizandrin high dose+SDF-1/CXCR4 pathway inhibitor(AMD3100,40 mg/kg+5 mg/kg)group,with 12 rats in each group.Another 12 rats were selected as sham operation group(only exposed the ovaries without removal during the operation).After modeling,rats in each group received corresponding drug intervention,once a day for 12 weeks.Bone mineral density(BMD)of the left and right femur was detected with dual energy X-ray absorptiometry.Serum levels of C-telopeptide of type I collagen(CTX-Ⅰ)and osteocalcin(OC)were detected with enzyme linked immunosorbent assay.HE staining was used to observe the pathological changes of the rat femur.mRNA levels of SDF-1 and CXCR4 in the rat femoral tissue were detected with fluorescence quantitative PCR.Protein levels of SDF-1 and CXCR4 in the rat femoral tissue were detected with Western blotting.Results In the sham operation group,the structure of bone trabeculae in the femoral tissue was normal and arranged regularly.Compared with those in sham operation group,the bone trabeculae in the femoral tissue of the model group rats were sparsely broken,the number was reduced,and the arrangement was disordered.BMD of the left and right femur,serum OC and CTX-Ⅰlevels,and SDF-1 and CXCR4 mRNA and protein levels in the femoral tissue decreased significantly(P<0.05).Compared with those in the model group,the degree of femoral tissue lesions in the deoxyschizandrin low and high dose groups reduced gradually,BMD of the left and right femur,the levels of OC and CTX-Ⅰin serum,and the levels of SDF-1 and CXCR4 mRNA and protein in the femoral tissue increased gradually(P<0.05

关 键 词：五味子甲素 骨质疏松症大鼠 基质细胞衍生因子-1 CXC趋化因子受体4 

分 类 号：R285.5[医药卫生—中药学]