伊班膦酸钠对卵巢切除大鼠骨质疏松的干预效应(英文)

Interventional effect of ibandronate on osteoporosis in ovariectomized rats

背景:双膦酸盐在临床绝经后妇女骨质疏松症防治中疗效显著,而伊班膦酸钠作为新型双膦酸盐制剂正逐渐成为研究热点。目的:通过观察卵巢切除大鼠骨量丢失的相关指标,探讨伊班膦酸钠干预卵巢切除大鼠骨质疏松的有效性,并与尼尔雌醇比较。设计:完全随机分组,对照动物实验。单位:复旦大学医学院骨代谢研究室。材料:选用SD雌性大鼠40只,鼠龄10～12个月。伊班膦酸钠由江苏原子医学研究所国家重点实验室提供。尼尔雌醇由上海第十二制药厂生产。方法:实验于1996-08/1998-06在上海医科大学放射医学研究所骨代谢研究室完成。采用随机抽签法分为4组,每组10只。假手术组:仅切除卵巢周围小块脂肪组织,手术3个月后每天灌胃生理盐水1mL/只;卵巢切除组、卵巢切除+伊班膦酸钠组、卵巢切除+尼尔雌醇组:均行双侧卵巢切除,3个月后分别开始灌服生理盐水、伊班膦酸钠0.5mg/(kg·d)水溶物、尼尔雌醇混悬液1mg/(kg·次)。给药组均于给药第1周灌药2次,以后每周1次,均给药90d。主要观察指标:取左侧股骨,测其干重、灰重,采用PE23110型原子吸收分光光度计测定骨钙含量。采用DPX-L型骨密度测定全身骨密度;采用SPA型单光子大鼠骨密度仪测右侧股骨全长1/2交界处的骨密度。采用AG22020KNA型万能材料试验机测定股骨抗弯力。采用动力学法由ENCORⅡ型自动生化分析仪测定血碱性磷酸酶活性,采用EDTA滴定法测定尿钙,采用苦味酸法测定尿肌酐;采用改良血尿羟脯氨酸测定法测定尿羟脯氨酸。计算骨小梁面积。结果:大鼠40只均进入结果分析。①骨干重、灰重和钙含量的改变:卵巢切除组大鼠骨干重、灰重和钙含量明显低于其他3组(t=13.58～52.98,P<0.05)。②股骨骨密度、抗弯力和全身骨密度的改变:卵巢切除组大鼠股骨骨密度和全身骨密度明显低于其他3组(t=3.31～5.61,P<0.05),而抗弯力与其他3组相近(P>0.05)。③血碱性磷酸酶及尿羟脯氨酸与肌酐、钙与肌酐比值的改变:卵巢切除+伊班膦酸钠组和卵巢切除+尼尔雌醇组大鼠尿钙与肌酐比值明显低于卵巢切除组(t=4.04,3.30,P<0.05),其他2项指标在各组间比较,差异无显著性意义(P>0.05)。④椎骨、胫骨骨小梁面积的改变:卵巢切除组大鼠椎骨骨小梁面积明显小于其他3组(t=2.22,2.41,3.45,P<0.05),而胫骨骨小梁面积仅卵巢切除+尼尔雌醇组明显大于卵巢切除组(t=2.45,P<0.05)。结论:SD大鼠卵巢切除3个月后出现明显的骨质疏松,伊班膦酸钠对卵巢切除骨质疏松模型大鼠骨量的丢失有显著抑制作用,且与尼尔雌醇作用相当。

BACKGROUND： Diphosphonate has a predominant therapeutic effect in the prevention and treatment of postmenopausal osteoporosis. Ibandronate, as a new-type diphosphonate preparation, is gradually becoming a study hotspot. OBJECTIVE： This study is to investigate the efficiency of ibandronate in interfering postmenopausal osteoposis by observing bone mass loss related indexes in ovariectomized rats, and made a comparison with nilestriol. DESIGN： A completely randomized grouping, and controlled animal experiment SETTING： Study Room for Bone metabolism, Fudan University Medical College MATERIALS： Forty SD female rats, aged 10-12 months, were involved in this study. Ibandronate was provided by the State Key Laboratory of Jiangsu Institute of Atomic Medicine. Nilestriol was produced in the Shanghai 12th Pharmaceutical Factory. METHODS： This experiment was carried out in the Study Room for Bone Metabolism, Institute of Radiation Medicine, Shanghai Medical University between August 1996 and June 1998. The rats were divided into 4 groups by a lot, 10 rats in each： sham-operation group, ovariectomized group, ovariectomized＋ibandronate group and ovariectomized ＋nilestriol group. In the sham-operation group, only small pieces of adipose tissue around the ovary were resected from the rats. Three months after operation, each rat was intragastrically administrated with 1 mL normal saline; In the ovariectomized group, ovariectomized＋ibandronate group and ovariectomized ＋nilestriol group, each rat was subjected to bilateral ovariectomy, and 3 months later, they were intragastrically administrated with normal saline, ibandronate water solution [0.5 mg/（ kg·d）] and nilestriol suspension [1 mg/（kg·time）] respectively. Each rat in the latter three groups was administrated for 90 days, twice in the first week, and then once a week. MAIN OUTCOME MEASURES： Left femur was taken out, and its dry weight and ash weight were measured. Calcium content of bone was determined with an atomic absorption spectrophotometer, bone density of the whole body with a bone density apparatus, the bone density at the juncture of 1/2 right femoral bone length with a single photon bone density apparatus, and femoral anti-bending force was determined with a universal testing machine. Alkaline phosphatase were determined by dynamical method with an automatic biochemistry analyzer, urine calcium by EDTA titration method, urine creatinine by picric kinetic method, and urinary hydroxyproline by modified proline assay. Trabecular area was calculated. RESULTS ： Forty rats were involved in the final analysis. ①Bone dry weight, bone ash weight and bone calcium content in the ovariectomized group were significantly lower than those in the other 3 groups, respectively （t =13.58-52.98, P 〈 0.055）. ② Femoral bone density and bone density of the whole body of rats in the ovariectomized group were significantly lower than those in the other 3 groups （t =3.31-5.61, P 〈 0.05）, while anti-bending force was close between ovariectomized group and the other 3 groups （P 〉 0.05）. ③The ratio of urine calcium to urine creatinine was significantly lower in the ovariectomized＋ibandronate group and ovariectomized ＋nilestriol group than in the ovariectomized group （t =4.04, 3.30, P 〈 0.055. No significant difference in the alkaline phosphatase and ratio of urinary hydroxyproline to urinary creatinine existed among the groups （P 〉 0.055. ④Trabecular area of vertebrae in the ovariectomized group was significantly smaller than that in the other 3 groups （t =2.22,2.41,3.45,P 〈 0.05）, while the trabecular area of tibia in the ovariectomized group was only smaller than that in the ovariectomized ＋nilestriol group （t =2.45, P〈 0.055. CONCLUSION： Osteoporosis appears obviously in the SD rats 3 months after ovariectomy. Ibandronate has obviously inhibitory effects on the bone mass loss of rats with postmenopausal osteoposis, and it is equivalent to nilestriol in inhibitory effect.