新仙灵骨葆胶囊调控成骨细胞G1期调节蛋白抗骨质疏松的实验研究

Study on Anti-Osteoporosis Action of New Xianling Gubao Capsule by Regulating Osteoblast G1 Phase Regulatory Protein

目的：观察新仙灵骨葆胶囊调控成骨细胞G1期调节蛋白抗去卵巢大鼠骨质疏松的作用。方法：去卵巢制备大鼠骨质疏松模型,大鼠随机分为假手术组,模型组,仙灵骨葆胶囊组（350 mg/kg）,新仙灵骨葆胶囊低、中、高剂量组（53、105、210 mg/kg）,各组灌胃相应药物10 m L/kg,连续12周。末次给药后进行骨密度仪分析大鼠的椎骨、股骨、胫骨的骨密度;检测股骨生物力学性能;计算子宫指数;取第3腰椎,免疫组织化学方法检测成骨细胞中细胞周期蛋白D1（Cyclin D1）、细胞周期蛋白依赖激酶（CDK4）、癌基因蛋白p21的表达。结果：与模型组比较,新仙灵骨葆胶囊可显著抑制大鼠体质量,增加子宫指数和椎骨、股骨、胫骨的骨密度,改善大鼠的生物力学性能,降低第3腰椎成骨细胞Cyclin D1、CDK4、p21蛋白水平。结论：新仙灵骨葆胶囊对去卵巢大鼠所致的骨质疏松症有良好的治疗效果,其作用机制可能是通过调控成骨细胞G1期调节蛋白而影响成骨细胞增值。

Objective：To explore the anti-osteoporosis action of New Xianling Gubao Capsule by regulating osteoblast G1 phase regulatory protein. Methods：The rat model of osteoporosis was induced through ovariectomy. The rats were evenly randomized into 6 groups,namely sham operation group,model group,Xianling Gubao Capsule group（350 mg/kg）,and low-dose,middle-dose and high-dose new Xianling Gubao Capsule groups（ in the dose of 53,105,210 mg/kg respectively）. The corresponding drug was given by oral administration with 10 m L/kg for 12 weeks,and then bone mineral densities（ BMD） of the vertebra,femur and tibia were measured. Uterine was removed from each rat and immediately weighed and the femur was taken out for biomechanical measurements. The third lumbar vertebra were removed from rats and immediately soaked with formaldehyde,and then the expressions of cyclin D1,cyclin dependent kinase（ CDK4） and oncogene protein p21（ p21） proteins were detected by immunohistochemical method. Results：According to the results,compared with the model group,New Xianling Gubao Capsule obviously inhibited the body weight and the levels of cyclin D1,CDK4 and p21 proteins of osteoblast,and increaced the BMD of the vertebra,femur and tibia,the uterine index and the biomechanical strength（ P〈0. 05 or P〈0. 01）. Conclusion：New Xianling Gubao Capsule has significant anti-osteoporosis effect. Its mechanism may be through regulation of G1 phase regulatory protein of osteoblasts and inhibiting osteoblast increment.