论文部分内容阅读
目的:观察携带人骨保护素基因的重组腺病毒(recombinantadenovirusvectorcarryinghumanosteoprotegeringene,Ad-hOPG)在大鼠体内表达及对去势骨质疏松大鼠的治疗作用。方法:首先将不同滴度的Ad-hOPG(1×1011~1×1013pfu/L)注入SD大鼠体内,观察其表达特点。然后选用10月龄雌性SD大鼠15只,随机分为假手术对照组、卵巢切除+生理盐水注射组、卵巢切除+Ad-hOPG治疗组,每组5只,分别在去势8周后开始给药,给药后在不同时像点测定人骨保护素(humanosteoprotegerin,hOPG)血清浓度;在给药后第48d时用双能X射线骨密度仪(dualenergyXrayabsorptiometry,DEXA)测定各组大鼠骨密度值,并取大鼠胫骨干骺端做组织切片。结果:1×107~1×109pfu的Ad-hOPG表达时限较短,1×1010pfu则表达了长达46d,选择1×1010pfu做进一步实验;假手术对照组、卵巢切除+生理盐水注射组没能检测到hOPG的血清浓度,而卵巢切除+Ad-hOPG治疗组hOPG的血清浓度第2天就达到25mg/L,6d达到高峰,46d时仍有0.0042mg/L;卵巢切除+Ad-hOPG治疗组的骨密度值明显高于卵巢切除+生理盐水注射组(P<0.01),甚至比假手术对照组还高;卵巢切除+Ad-hOPG治疗组大鼠骨形态学也较假手术对照组明显改善。结论:Ad-hOPG在大鼠体内成功的较长时间表达,对去势大鼠骨质疏松治疗取得
OBJECTIVE: To observe the expression of recombinant adenovirus vector carrying human osteoprotegerin (Ad-hOPG) in rats and the therapeutic effect on osteoporosis rats. Methods: Ad-hOPG (1 × 10 11 ~ 1 × 10 13 pfu / L) with different titer was injected into SD rats firstly to observe its expression characteristics. Then, 15 female 10-month-old female SD rats were randomly divided into sham-operated control group, ovariectomized + saline injection group and ovariectomized + Ad-hOPG treatment group, with 5 rats in each group. After 8 weeks of castration, The serum concentrations of humanosteoprotegerin (hOPG) were measured at different time points after administration. The bone mineral density (BMD) of each group was measured by dualenergy Xray absorption spectrometry (DEXA) Value, and take the tibial metaphyseal tissue slices. Results: The expression of Ad-hOPG from 1 × 107 to 1 × 109 pfu was shorter than that from 1 × 1010 pfu for up to 46 days, and 1 × 1010 pfu was selected for further experiments. In the sham operation group and ovariectomized + saline injection group, The serum concentration of hOPG was detected in ovariectomized + Ad-hOPG group, the serum concentration of hOPG in ovariectomized + Ad-hOPG group reached 25mg / L on the second day, peaked on the 6th day and 0.0042mg / L on the 46th day. (P <0.01), even higher than sham-operated control group. The bone morphological changes in ovariectomized + Ad-hOPG-treated group were also significantly improved compared with sham operation control group . Conclusion: Ad-hOPG was successfully expressed in rats for a long time and was obtained in the treatment of osteoporosis in ovariectomized rats