雌性去势大鼠骨质疏松症与胰淀素的治疗效应

Osteoporosis and the therapeutic effect of amylin in female ovariomotized rats

目的:探讨胰淀素对去势雌性大鼠骨质疏松症的干预作用。方法:实验于2003-02/2004-05在解放军第三军医大学大坪医院野战外科研究所妇产科实验室完成。选用3月龄Wistar大鼠40只,随机分为3组:正常组(n=8)、去势组(n=8)、胰淀素治疗组(n=24)。胰淀素治疗组按治疗剂量分为3组:10μg/kg组(n=8),50μg/kg组(n=8)和250μg/kg组(n=8)。正常组不作任何处理,不造成骨质疏松模型;去势组予以同量生理盐水注射;胰淀素治疗组给予胰淀素相应剂量皮下注射,1次/d。16周后行骨密度、骨生物力学及血、尿生化检查。结果:40只大鼠均完成实验。①大鼠腰椎和股骨骨密度:去势组均明显低于正常组(t=3.125,3.367,P<0.01),胰淀素治疗组明显高于去势组(t=2.895～4.589,P<0.01)。其中以50和250μg/kg胰淀素干预治疗后骨密度接近于正常组。②尿钙、尿磷、尿羟脯氨酸值:胰淀素治疗组明显低于去势组(t=2.578～4.487,P<0.01)。③血骨钙素:正常组明显高于去势组犤(1.33±0.25),(0.88±0.18)μg/L,P<0.01犦;胰淀素治疗组明显高于去势组犤(0.97±0.17),(1.18±0.21),(1.24±0.22)μg/L;(0.88±0.18)μg/L,t=2.698,3.358,4.438,P<0.01犦。④股骨最大负荷、最大应变、最大应力变化:胰淀素治疗组明显高于去势组(t=2.958～4.258,P<0.01),250μg/kg胰淀素治疗组大鼠股骨力学指标接近正常组。⑤血清及尿生化指标变化:以250μg/kg胰淀素治疗后最接近正常组。结论:胰淀素治疗可以增加去势大鼠骨密度,提高大鼠股骨生物力学性能。生化检查提示胰淀素不仅可以促进骨形成,同时还具有抑制骨吸收的作用,其改善血尿生化指标及骨生物力学性能以250μg/kg胰淀素干预效果最好。

AIM:To investigate the interventional effect of amylin on osteoporosis in female ovariotomized rats.METHODS:The experiment was carried out in the laboratory of Department of Obstetrics and Gynecology,Research Institute of Surgery,Daping Hospital,Third Military Medical University of Chinese PLA between February 2003 and May 2004.Forty 3 month old Wistar rats were randomly divided into 3 groups:normal group(n=8),ovariotomized group(n=8) and amylin treated group(n=24),and the amylin group was subdivided into 10 μ g/kg group(n=8),50 μ g/kg group(n=8) and 250 μ g/kg group(n=8).Rats in the normal group received no treatment,and were not made into models of osteoporosis;Rats in the ovariomotized group were injected with saline of the same volume;Rats in the amylin treated groups received subcutaneous injection of amylin of corresponding dosages, once a day.After 16 weeks,bone mineral density,bone biomechanics, and blood and uric biochemical examinations were detected.RESULTS:All the 40 rats finished the experiment.① The bone mineral densities at lumbar spine and femur were obviously lower in the ovariotomized group than in the normal group(t=3.125,3.367,P< 0.01),markedly higher in the amylin treated group than in the ovariotomized group(t=2.895 to 4.589,P< 0.01);After treatment,the bone mineral densities in the 50 and 250 μ g/kg amylin groups were close to those in the normal group.② The values of calcium, phosphorus and hydroxyproline in urine were obviously lower in the amylin treated groups than in the ovariotomized group(t=2.578 to 4.487,P< 0.01).③ Blood osteocalcin level was obviously higher in the normal group than in the ovariotomized group[(1.33± 0.25),(0.88± 0.18) μ g /L,P< 0.01],markedly lower in the amylin treated groups than in the ovariotomized group[(0.97± 0.17),(1.18± 0.21),(1.24± 0.22) μ g /L,(0.88± 0.18) μ g /L,t=2.698,3.358,4.438,P< 0.01].④ The maximal load, the maximal strain and the change of the maximal strain were obviously higher in the amylin treated groups than in the ovariotomized group(t=2.958 to 4.258, P< 0.01),the mechanic indexes of femur in the 250 μ g/kg amylin treated group were close to those in the normal group.⑤ After treatment,the changes of biochemical indexes in serum and urine in the 250 μ g/kg amylin treated group were the closest to those in the normal group.CONCLUSION:Amylin treatment can increase the bone mineral density of ovariotomized rats,and improve their biomechanic functions of femur.Biochemical examination indicates that amylin can not only promote bone formation, but also inhabit bone resorption,and the interventional effects of 250 μ g/kg amylin are the best in ameliorating biochemical indexes in blood and urine and biomechanic functions.