骨硬化蛋白单克隆抗体单用与联合黄芪对去卵巢诱导的骨质疏松疗效比较
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摘要
目的:探讨骨硬化蛋白单克隆抗体(Scl-Ab)单用与联合黄芪对去卵巢诱导的骨质疏松治疗效果的比较。方法:随机将30只雌性健康SD大鼠行切除双侧卵巢手术(OVX组,n=25)和假手术(Sham组,n=5),手术12周后各取5只大鼠处死并取股骨行Micro-CT检测骨质疏松动物模型是否建立。建模成功后将OVX组大鼠随机分成2组:Scl-Ab组和Scl-Ab+黄芪组。术后第1天Scl-Ab+黄芪组给予药物治疗:Scl-Ab皮下注射(12.5 mg/kg,每周2次);同时每天给于200 mg/kg黄芪液灌胃,直至12周。Scl-Ab组则给予Scl-Ab皮下注射(25 mg/kg,每周2次),并且每天给予200 mg/kg 0.9%氯化钠溶液灌胃,直至12周。用药12周时处死所有大鼠并取股骨行Micro-CT、硬组织切片检测。结果:与Scl-Ab组比,Scl-Ab+黄芪组大鼠股骨远端有较高的股骨BMD、BV/TV、Tb.Th、Tb.N、Conn.D、MAR和较低的Tb.Sp,差异有统计学意义(P<0.05)。结论:Scl-Ab联合黄芪对去卵巢诱导的大鼠骨质疏松治疗效果要优于单用Scl-Ab。
Objective: To compare the therapeutic effect of Sclerostin-antibody and Sclerostin-antibody with Astragalus membranaceus on osteoporosis in OVX rats. Methods: Bilateral ovariectomy(OVX, n=25) and sham(Sham, n=5) operation were performed in 30 healthy female SD rats at random. After 12 weeks, 5 rats in each group were executed and their femurs were taken for micro-CT to detect whether the osteoporosis animal model was established. When the model of osteoporosis is established successfully, all animals from OVX(n=20) group randomly divided into two groups:group Scl-Ab+Astragalus membranaceus and group Scl-Ab. Then group Scl-Ab+Astragalus membranaceus was given Scl-Ab(12.5 mg/kg, two times a week) by hypodermic injection and Astragalus membranaceus extract [200 mg/(kg·d), once a day] by gavage, Scl-Ab group was given Scl-Ab(25 mg/kg, two times a week) by hypodermic injection and saline [200 mg/(kg·d), once a day] by gavage. The femurs of rats were harvested for evaluation. The results of treatment for osteoporosis were evaluated by microcomputerized tomography and undecalcified sliced. Results: Compared with group Scl-Ab, the distal femurs from group Scl-Ab+astragalus membranaceus have a higher BMD, BV/TV, Tb.Th, Tb.N, Conn. D bone mineral apposition rates and a lower Tb.Sp. Conclusion: The results of this study indicates that Sclerostin-antibody with Astragalus membranaceus is superior to Sclerostin-antibody only in the treatment of ovariectomized osteoporosis in rats.
Objective: To compare the therapeutic effect of Sclerostin-antibody and Sclerostin-antibody with Astragalus membranaceus on osteoporosis in OVX rats. Methods: Bilateral ovariectomy(OVX, n=25) and sham(Sham, n=5) operation were performed in 30 healthy female SD rats at random. After 12 weeks, 5 rats in each group were executed and their femurs were taken for micro-CT to detect whether the osteoporosis animal model was established. When the model of osteoporosis is established successfully, all animals from OVX(n=20) group randomly divided into two groups:group Scl-Ab+Astragalus membranaceus and group Scl-Ab. Then group Scl-Ab+Astragalus membranaceus was given Scl-Ab(12.5 mg/kg, two times a week) by hypodermic injection and Astragalus membranaceus extract [200 mg/(kg·d), once a day] by gavage, Scl-Ab group was given Scl-Ab(25 mg/kg, two times a week) by hypodermic injection and saline [200 mg/(kg·d), once a day] by gavage. The femurs of rats were harvested for evaluation. The results of treatment for osteoporosis were evaluated by microcomputerized tomography and undecalcified sliced. Results: Compared with group Scl-Ab, the distal femurs from group Scl-Ab+astragalus membranaceus have a higher BMD, BV/TV, Tb.Th, Tb.N, Conn. D bone mineral apposition rates and a lower Tb.Sp. Conclusion: The results of this study indicates that Sclerostin-antibody with Astragalus membranaceus is superior to Sclerostin-antibody only in the treatment of ovariectomized osteoporosis in rats.
引文
[1]PENG L,LUO Q,LU H.Efficacy and safety of bazedoxifene in postmenopausal women with osteoporosis:A systematic review and meta-analysis[J].Medicine(Baltimore),2017,96(49):e8659.
[2]赖宪良,苏嘉,陈鸥.CXCL12对RANKL诱导的RAW264.7细胞向破骨细胞分化的影响[J].温州医科大学学报,2018,48(3):216-219,224.
[3]SI L,WINZENBERG T M,JIANG Q,et al.Projection of osteoporosis-related fractures and costs in China:2010-2050[J].Osteoporos Int,2015,26(7):1929-1937.
[4]RUSSEL B,BESS D H,SOLOMON D H,et al.Incidence and economic burden of osteoporosis-related fractures in the United States,2005-2025[J].J Bone Miner Res,2007,22(3):465-475.
[5]LIESBETH V,BEHETS G J,KATHLEEN C,et al.Sclerostin:another bone-related protein related to all-cause mortality in haemodialysis?[J].Nephrol Dial Transplant,2013,28(12):3024-3030.
[6]方淑斌,田京.骨硬化蛋白在骨质疏松治疗中的研究进展[J].实用医学杂志,2014,30(4):659-661.
[7]FUKUMOTO S,MATSUMOTO T.Recent advances in the management of osteoporosis[J].F1000Res,2017,6:625.
[8]杨立宇,付勤.骨硬化蛋白单克隆抗体治疗骨质疏松新进展[J].中华骨质疏松和骨矿盐疾病杂志,2017,10(2):179-185.
[9]潘静华,张海啸,李芳芳,等.黄芪对去卵巢大鼠骨组织的动态影响[J].中国中医基础医学杂志,2010,16(3):251-253.
[10]阳波,杨静.黄芪对绝经后骨质疏松症患者影响的临床研究[J].四川医学,2007,28(3):291-293.
[11]崔红,贾文斌,杨奇,等.黄芪治疗绝经后骨质疏松的抗氧化机制研究[J].国际妇产科学杂志,2015,42(5):504-507.
[12]谢辉.骨硬化蛋白单克隆抗体对于有去卵巢大鼠骨折愈合影响的实验研究[J].中国骨质疏松杂志,2017,23(1):12-15.
[13]YAO W,DAI W,JIANG L,et al.Sclerostin-antibody treatment of glucocorticoid-induced osteoporosis maintained bone mass and strength[J].Osteoporosis Int,2015,27(1):283-294.
[14]吴海洋,索欢,王平.绝经后骨质疏松症的临床中药治疗进展[J].中国骨质疏松杂志,2015,21(2):241-244.
[15]刘学军.骨质疏松症[J].中国矫形外科杂志,2006,14(21):1668-1670.
[16]严红梅,张振海,孙娥,等.中药治疗骨质疏松症的研究进展[J].中草药,2014,45(8):1174-1178.
[17]WARRINER A H,SAAG K G.Osteoporosis diagnosis and medical treatment[J].Ortho Clin North Am,2013,44(2):125-135.
[18]YEE A J,RAJE N S.Denosumab,a RANK ligand inhibitor,for the management of bone loss in cancer patients[J].Clin Interv Aging,2012,7(12):331-338.
[19]LI X,OMINSKY M S,WARMINGTON K S,et al.Sclerostin antibody treatment increases bone formation,bone mass,and bone strength in a rat model of postmenopausal osteoporosis[J].J Bone Miner Res,2009,24(4):578-588.
[20]高德富,刘晓蕙,樊剑鸣,等.黄芪提取物对小鼠生长性能、抗氧化及免疫功能的影响[J].航空航天医学杂志,2011,22(2):144-145,147.
[21]陈华庭,王虎,郑菁,等.黄芪总黄酮提取物对维甲酸所致大鼠骨质疏松的影响[J].中国药师,2005,8(11):895-897.
[2]赖宪良,苏嘉,陈鸥.CXCL12对RANKL诱导的RAW264.7细胞向破骨细胞分化的影响[J].温州医科大学学报,2018,48(3):216-219,224.
[3]SI L,WINZENBERG T M,JIANG Q,et al.Projection of osteoporosis-related fractures and costs in China:2010-2050[J].Osteoporos Int,2015,26(7):1929-1937.
[4]RUSSEL B,BESS D H,SOLOMON D H,et al.Incidence and economic burden of osteoporosis-related fractures in the United States,2005-2025[J].J Bone Miner Res,2007,22(3):465-475.
[5]LIESBETH V,BEHETS G J,KATHLEEN C,et al.Sclerostin:another bone-related protein related to all-cause mortality in haemodialysis?[J].Nephrol Dial Transplant,2013,28(12):3024-3030.
[6]方淑斌,田京.骨硬化蛋白在骨质疏松治疗中的研究进展[J].实用医学杂志,2014,30(4):659-661.
[7]FUKUMOTO S,MATSUMOTO T.Recent advances in the management of osteoporosis[J].F1000Res,2017,6:625.
[8]杨立宇,付勤.骨硬化蛋白单克隆抗体治疗骨质疏松新进展[J].中华骨质疏松和骨矿盐疾病杂志,2017,10(2):179-185.
[9]潘静华,张海啸,李芳芳,等.黄芪对去卵巢大鼠骨组织的动态影响[J].中国中医基础医学杂志,2010,16(3):251-253.
[10]阳波,杨静.黄芪对绝经后骨质疏松症患者影响的临床研究[J].四川医学,2007,28(3):291-293.
[11]崔红,贾文斌,杨奇,等.黄芪治疗绝经后骨质疏松的抗氧化机制研究[J].国际妇产科学杂志,2015,42(5):504-507.
[12]谢辉.骨硬化蛋白单克隆抗体对于有去卵巢大鼠骨折愈合影响的实验研究[J].中国骨质疏松杂志,2017,23(1):12-15.
[13]YAO W,DAI W,JIANG L,et al.Sclerostin-antibody treatment of glucocorticoid-induced osteoporosis maintained bone mass and strength[J].Osteoporosis Int,2015,27(1):283-294.
[14]吴海洋,索欢,王平.绝经后骨质疏松症的临床中药治疗进展[J].中国骨质疏松杂志,2015,21(2):241-244.
[15]刘学军.骨质疏松症[J].中国矫形外科杂志,2006,14(21):1668-1670.
[16]严红梅,张振海,孙娥,等.中药治疗骨质疏松症的研究进展[J].中草药,2014,45(8):1174-1178.
[17]WARRINER A H,SAAG K G.Osteoporosis diagnosis and medical treatment[J].Ortho Clin North Am,2013,44(2):125-135.
[18]YEE A J,RAJE N S.Denosumab,a RANK ligand inhibitor,for the management of bone loss in cancer patients[J].Clin Interv Aging,2012,7(12):331-338.
[19]LI X,OMINSKY M S,WARMINGTON K S,et al.Sclerostin antibody treatment increases bone formation,bone mass,and bone strength in a rat model of postmenopausal osteoporosis[J].J Bone Miner Res,2009,24(4):578-588.
[20]高德富,刘晓蕙,樊剑鸣,等.黄芪提取物对小鼠生长性能、抗氧化及免疫功能的影响[J].航空航天医学杂志,2011,22(2):144-145,147.
[21]陈华庭,王虎,郑菁,等.黄芪总黄酮提取物对维甲酸所致大鼠骨质疏松的影响[J].中国药师,2005,8(11):895-897.