低分子肝素与普通肝素对慢性肾脏病大鼠肾性骨病及血管钙化影响的比较研究
Effects of low molecular weight heparin on renal osteodystrophy and vascular calcification in chronic kidney disease rats: comparing with unfractionated heparin
  
DOI:10.3969/j.issn.1006-7108.2018.02.009
中文关键词:  慢性肾脏病  肾性骨病  血管钙化  低分子肝素  继发性甲状旁腺功能亢进症  生物力学  骨质疏松  动物实验
英文关键词:Chronic kidney disease  Renal osteodystrophy  Vascular calcification  Low molecular weight heparin  Secondary hyperparathyroidism  Biomechanics  Osteoporosis  Animal experimentation
基金项目:内蒙古自然科学基金博士基金项目(2014BS0807);内蒙古医科大学附属医院博士科研启动基金(NYFYBS2015013);北京市自然科学基金项目(7162193);第五批内蒙古“草原英才”基金项目内蒙古医科大学附属医院肾内科创新人才团队基金
作者单位
孟彦1* 张豪2 贺宁1 石东英1 赵建荣1 李青南3,4 左力5* 1.内蒙古医科大学附属医院肾内科内蒙古 呼和浩特 010050 2.湖北医药学院口腔医学部湖北 十堰 442000 3.广东药科大学生命科学与生物制药学院广东 广州 510006 4.广东实验动物监测所/广东省实验动物重点实验室广东 广州 510663 5.北京大学人民医院肾内科北京 100044 
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中文摘要:
      目的 用腺嘌呤诱导的慢性肾脏病(chronic kidney disease,CKD)大鼠模型观察低分子肝素(low molecular weight heparin,LMWH)对CKD时肾性骨病和血管钙化的影响,与普通肝素(unfractionated heparin,UFH)进行比较。方法 50只雄性SD大鼠随机分为正常对照组、CKD组、CKD普通肝素组(CKD Heparin)、慢性肾脏病低剂量LMWH组(CKD L-LMWH)、慢性肾脏病高剂量LMWH组(CKD H-LMWH)5组。第6周末处死大鼠,行主动脉血管钙磷含量测定,取股骨和第5腰椎做骨密度(bone mineral density,BMD)检查、腰椎压缩试验、三点弯曲试验。结果 与CKD组比较,CKD Heparin组、CKD L-LMWH组、CKD H-LMWH组血管钙磷水平没有统计学差异。与CKD组比较,CKD Heparin组的股骨总BMD、股骨松质骨BMD和腰椎BMD均明显降低,而CKD L-LMWH组和CKD H-LMWH组与CKD组比较上述参数无明显差异。与CKD组比较,CKD Heparin组、CKD L-LMWH组和CKD H-LMWH组的股骨皮质骨BMD无明显差异。腰椎压缩试验,与CKD组比较,CKD Heparin组的结构力学和材料力学参数明显降低,CKD L-LMWH组和CKD H-LMWH组分别与CKD组比较上述力学参数无差异。三点弯曲试验,与CKD组比较,CKD Heparin、CKD L-LMWH组或CKD H-LMWH组力学参数均无差异。结论 LMWH对有继发性甲旁亢的CKD大鼠的松质骨BMD和骨力学参数无影响,而UFH可以降低松质骨的BMD和骨力学性能;LMWH和UFH对有继发性甲旁亢的CKD大鼠的皮质骨BMD和骨力学性能无影响。LMWH和UFH对有继发性甲旁亢的CKD大鼠的血管钙化无影响。
英文摘要:
      Objective To study the effects of low molecular weight heparin (LMWH) on renal osteodystrophy and vascular calcification in chronic kidney disease (CKD) rats, compared with unfractionated heparin (UFH). Methods CKD model with secondary hyperparathyroidism was established by feeding adenine diet to rats. 50 male SD rats were divided into five groups randomly for six weeks’ raising: (1) Normal group; (2) CKD group; (3) CKD unfractionated heparin (UFH) group(CKD heparin); (4) CKD low-dose LMWH group(CKD L-LWH); (5) CKD high-dose LMWH group(CKD H-LWH). The normal control group was feed with diet without adenine and the other 4 groups were raised by adenine-contained diet for the first 4 weeks and diet without adenine for the following 2 weeks. Six weeks later, calcium and phosphorus contents of the abdominal aorta were tested using spectrum analysis and bone mineral density (BMD) and biomechanical parameters were determined in femurs and lumbar 5. Results Compared with CKD group, there was no statistical difference about vascular calcium or phosphorus content in CKD heparin group, CKD L-LWH group or CKD H-LWH group. Compared with CKD group, femur total BMD and femur trabecular BMD and lumbar BMD were lower significantly in CKD heparin group and there was no difference between CKD group, CKD L-LWH group and CKD H-LWH group in femur total BMD and femur trabecular BMD and lumbar BMD. No difference was found in femur cortical BMD between CKD group, CKD heparin group, CKD L-LWH group and CKD H-LWH group. In lumbar compression test, the structural and material biomechanical parameters (maximum load, stiffness, maximum stress and elastic modulus) were reduced significantly in CKD heparin group, compared with CKD group and there was no difference between CKD group, CKD L-LWH group and CKD H-LWH group about these lumbar biomechanical parameters. In three-point bending test, no difference was found between CKD group, CKD heparin group, CKD L-LWH group and CKD H-LWH group about the structural and material biomechanical parameters (maximum load, stiffness, maximum stress and elastic modulus). Conclusion LMWH had no effect on BMD and biomechanical parameters of trabecular bone in CKD rats with secondary hyperparathyroidism and UFH could reduce the BMD and biomechanical properties of trabecular bone in CKD rats with secondary hyperparathyroidism; both LMWH and UFH had no effect on BMD and biomechanical parameters of cortical bone in CKD rats with secondary hyperparathyroidism. Both LMWH and UFH had no effect on vascular calcification in CKD rats with secondary hyperparathyroidism.
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