硼替佐米诱导间充质干细胞治疗大鼠骨质疏松实验研究

Experimental Study of Mesenchymal Stem Cells Induced by Bortezomib in the Treatment of Osteoporosis in Rats

目的探讨硼替佐米诱导间充质干细胞分化治疗大鼠骨质疏松的疗效。方法选取75只健康雌性大鼠,建立大鼠去卵巢骨质疏松模型,并随机分为5组,测定5组大鼠的骨钙素水平。再选取75只健康大鼠,获取骨髓间充质干细胞,并按分组进行体外干细胞培养至形成集落。将形成的骨髓间质干细胞分别注入1~5组大鼠的骨髓腔中,并分别给予1~5组大鼠0,0.1,0.3,0.5,1.5 mg/kg硼替佐米4周,每日抽取大鼠的外周血测定骨钙素水平。4周后处死大鼠,取其长骨做切片,检测大鼠的骨密度、骨髓间充质干细胞增殖指数和凋亡指数。结果治疗前,5组大鼠骨钙素水平比较无明显差异(P>0.05),治疗后,5组大鼠骨钙素水平由高至低为1组、2组、3组、4组、5组;第5组大鼠的长骨骨密度和骨髓间充质干细胞增殖指数均高于其他4组大鼠(P<0.05),凋亡指数低于其他4组大鼠(P<0.05)。结论硼替佐米诱导间充质干细胞治疗大鼠去卵巢骨质疏松效果确切,在绝经后骨质疏松患者的临床治疗中应用可行。

Objective To investigate the clinical effect of mesenchymal stem cells induced by bortezomib in the treatment of osteoporosis in rats. Methods Totally 75 healthy female rats were selected to establish the ovariectomized osteoporosis model of rats and randomly divided into 5 groups. The osteocalcin levels of the 5 groups were measured. Another 75 healthy experimental rats were selected to obtain bone marrow mesenchymal stem cells, which were cultured in vitro until form a colony. The bone marrow mesenchymal stem cells were injected into the bone marrow cavity of the rats in the 5 groups, rats in group 1-5 were given 0, 0. 1, 0. 3, 0. 5, 1. 5 mg/kg bortezomib for 4 weeks, the peripheral blood of rats was extracted daily and osteocalcin levels were measured. After 4 weeks, the rats were killed, and the long bones of the rats were taken for sections, the bone mineral density, proliferation index and apoptosis index of bone marrow mesenchymal stem cells were measured. Results There was no significant difference in osteocalcin levels between the 5 groups before treatment （ P 〉 0. 05 ） , after treatment, the osteocalcin levels of the 5 groups were from high to low as follows：group 1, group 2, group 3, group 4, group 5. The bone density of the long bone and the proliferation indexes of bone and marrow mesenchymal stem cells in group 5 were significantly higher than those in the other 4 groups （ P 〈 0. 05 ） , and the apoptotic index in group 5 was lower than those in the other 4 groups （ P 〈 0. 05 ） . Conclusion Mesenchymal stem cells induced by bortezomib is effective in the treatment of ovariectomized osteoporosis in rats, and it is feasible in the clinical treatment of postmenopausal osteoporosis.