腺病毒介导人骨形态蛋白-7基因抑制去势大鼠骨质疏松的实验研究

Experimental study on osteoporosis of ovariectomized rats inhibited by adenovirus-BMP-7

[目的]探讨腺病毒介导骨形态蛋白-7基因转染对去势大鼠骨质疏松的抑制作用。[方法]用外科去势的方法造成大鼠骨质疏松动物模型,用腺病毒介导的骨形态蛋白-7基因通过椎体髓腔注射的方法转移至大鼠椎体内,骨干重测量来检测全身骨丢失的情况;骨组织形态学观察椎体骨小梁骨质疏松的情况;骨形态定量方法评价椎体骨小梁的动静态指标的变化情况。[结果]术后1个月的骨干重的测量显示注入AdBMP-7组的动物骨量明显大于其余各组;骨形态学检测结果显示注入AdBMP-7的椎体骨小梁结构较完整,而其余各组的骨小梁变细、断裂。5周后用骨形态定量进行检测显示AdBMP-7基因注入的椎体的各项动静态指标都明显优于其余各组椎体。[结论]腺病毒介导BMP-7基因植入去势大鼠椎体髓腔可以分泌BMP-7,并可以在早期阻止去势大鼠的骨质疏松。

[Objective] To evaluate the inhibiting affection of Ad-BMP-7 to osteoporosis of ovariectomized rats. [ Method] Mice model of osteoporosis was made by surgical ovariectomy, and divided into 4 groups： A. group of vertebral body intramedullary injection of normal saline; B. injection of Adovirus （Ad） -GFp; C. injection of Ad; D. injection of Ad ＋ BMP （ bone morphogenetie protein） , the bone losing of whole body were monitored by measuring dry bone weight after 1 month, the osteoporosic condition of bone trabeeular were observed by histology, and bone histomorphometry of vertebral bodies were carried to quatitatively measure the dynamic and static indexes of osteoporosie bone. [ Result] The dry bone weight of AdBMP-7 rats werehigher than that of other groups. Under the microscope, the bone trabeeula form of the Ad BMP-7 groups were more integrity, however, the bone trabecular of the other groups showed sharpen and ruptured. In the bone histomorphomitry, the numbers of the osteoblasts, the thickness of osteoid of group D were obviously higher than other groups. [ Conclusion] Ad BMP-7 injected into the vertebral bodies of ovarieetomized rats may secrete BMP-7, and inhibits the osteoporosis of ovarieetomized rats in the early stage. The protective effect of this gene was not restricted to bones receiving intramedullary injection of the vector, but occurred in all bones that were evaluated. This proof of concept encourages further development of gene therapy approaches to the treatment of osteoporosis.