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目的观察一种新型人甲状旁腺素相关肽(8L-hPTH)对去卵巢大鼠骨质疏松的治疗作用。方法88只3月龄SD健康雌性大鼠其中64只行双侧卵巢摘除术16只做假手术。3个月后各取8只测定腰椎及股骨骨密度。将余下的56只卵巢摘除大鼠随机分为7组每组8只,分别为8L-hPTH高、中、低剂量治疗组(剂量分别为20,10,5μg·kg-1·d-1);hPTH(1-34)高、中、低剂量对照组(剂量分别为20,10,5μg·kg-1·d-1);生理盐水组(0.5mL·d-1),各组均为皮下注射。假手术组余下的8只以及剩余8只未做任何手术的大鼠,给药方式及剂量均同生理盐水组。连续给药3个月后,比较各组大鼠股骨、腰椎骨密度并用扫描电镜观察股骨情况。结果双侧卵巢摘除3个月后,大鼠腰椎及股骨骨密度均明显低于假手术组(P<0.01),说明造模成功。给药3月后,8L-hPTH各治疗组大鼠与生理盐水组相比较,股骨、腰椎骨密度均显著升高(P<0.05),骨小梁宽度有极显著增加(P<0.001),效果呈剂量依赖性。结论皮下注射8L-hPTH(5～20μg·kg-1·d-1)对去卵巢骨质疏松大鼠有明显的治疗作用。
Objective To observe the therapeutic effect of a novel human parathyroid hormone related peptide (8L-hPTH) on osteoporosis in ovariectomized rats. Methods Totally 64 females aged 3 months and 3 healthy SD rats underwent bilateral ovariectomy for sham operation. Three months later, eight lumbar and femur BMD were measured. The remaining 56 ovariectomized rats were randomly divided into 7 groups of 8 rats each, which were 8L-hPTH high, medium and low dose treatment groups (doses of 20, 10, 5μg · kg-1 · d-1) ; high, middle and low doses of hPTH (1-34) (20, 10, 5μg · kg-1 · d-1, respectively); saline group (0.5mL · d-1) Subcutaneous injection. The remaining 8 sham-operation group and the remaining 8 rats without any surgery, administration and dosage were the same as the saline group. After 3 months of continuous administration, the femur and lumbar spine BMD of rats in each group were compared and the femur condition was observed with SEM. Results Three months after ovariectomy, the lumbar vertebral and femur BMD of rats were significantly lower than that of the sham-operated group (P <0.01), indicating successful modeling. Compared with the saline group, the bone mineral density of the femur and lumbar spine increased significantly (P <0.05) and the trabecular width increased significantly (P <0.001) The effect was dose-dependent. Conclusion Subcutaneous injection of 8L-hPTH (5 ~ 20μg · kg-1 · d-1) has obvious therapeutic effect on ovariectomized rats.