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不同时间点基因转染对下颌骨牵张成骨的影响。

Effect of gene transfecting at different times on mandibular distraction osteogenesis.

作者信息

Wu Guoping, Hu Chunbing, He Xiaochuan, Yin Kang, Lan Yongshu, Zhou Bin, Li Shaolan, Guo Li

机构信息

Department of Plastic Surgery, The Affiliated Friendship Plastic Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, 210029, China.

出版信息

J Craniofac Surg. 2013 Jan;24(1):232-6. doi: 10.1097/SCS.0b013e31826cff2a.

Abstract

BACKGROUND

Recently, numerous research of gene therapy for mandibular distraction has been published. Based on previous study, the authors used New Zealand rabbits bilateral mandibular distraction model and used electroporation mediate gene therapy at different time, to explore the optimal time for gene therapy and obtain a better effect.

METHODS

Forty-eight New-Zealand rabbits were used; after accomplished osteotomy and implant distraction devices on mandible bilaterly, the rabbits were randomly divided into 4 groups: groups A, B, and C were transfected recombinant plasmids pIRES-hBMP2-hVEGF165 via electroporation-mediated approach at latency period, distraction period, and consolidation period, respectively. Group D is a control group, only distracted without gene transfection. After 3 days of latency period, the device was activated at the rate of 1 mm per day for 10 days. Three rabbits of each group were sacrificed at 1, 2, 4, and 8 weeks of consolidation, respectively. The mandibles were harvested; the left was subject to radiograph examination for bone healing, and quantitative computed tomography detect for the bone mineral density (BMD) of newly formed bone in the distraction gap. The biomechanical properties of the new generation bone at the fourth and eighth weeks of consolidation of each group were detected using 3-point bending test.

RESULTS

The BMD and the stiffness of newly formed bone increased with the pass of the consolidation time in each group. After 1 week of consolidation, there is no significant difference of BMD among groups A, B, and C. However, the BMD of groups A, B, and C is higher than that of group D. After 2, 4, and 8 weeks of consolidation, the BMD of group B is significantly higher than those of groups A, C, and D. The biomechanical parameters are also higher in group B than those of groups A, C, and D after 4 and 8 weeks of consolidation.

CONCLUSIONS

It is better to transfect gene at distraction period than at other stages of DO; in this way, we can obtain more remarkable effect on new bone formation. It suggests that the distraction stage is the optimal time for gene therapy.

摘要

背景

近年来,已发表了大量关于下颌骨牵张成骨基因治疗的研究。基于先前的研究,作者采用新西兰兔双侧下颌骨牵张模型,并在不同时间采用电穿孔介导基因治疗,以探索基因治疗的最佳时机并获得更好的效果。

方法

使用48只新西兰兔;在双侧下颌骨完成截骨并植入牵张装置后,将兔随机分为4组:A组、B组和C组分别在潜伏期、牵张期和巩固期通过电穿孔介导的方法转染重组质粒pIRES-hBMP2-hVEGF165。D组为对照组,仅进行牵张而不进行基因转染。潜伏期3天后,以每天1毫米的速度激活装置,持续10天。每组分别在巩固期的1、2、4和8周处死3只兔。取下下颌骨;左侧进行X线检查以观察骨愈合情况,并通过定量计算机断层扫描检测牵张间隙中新形成骨的骨密度(BMD)。每组在巩固期第4周和第8周对新生骨进行三点弯曲试验以检测其生物力学性能。

结果

每组新形成骨的骨密度和硬度随巩固时间的推移而增加。巩固1周后,A组、B组和C组之间的骨密度无显著差异。然而,A组、B组和C组的骨密度高于D组。巩固2、4和8周后,B组的骨密度显著高于A组、C组和D组。巩固4周和8周后,B组的生物力学参数也高于A组、C组和D组。

结论

在下颌骨牵张成骨过程中,牵张期转染基因比其他阶段效果更好;通过这种方式,我们可以在新骨形成方面获得更显著的效果。这表明牵张期是基因治疗的最佳时机。

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