类胰岛素样生长因子1与明胶微球复合物对兔下颌骨缺损愈合影响的实验研究

发布时间：2018-06-26 02:22

本文选题：类胰岛素样生长因子1 + 明胶微球　；参考：《山西医科大学》2014年硕士论文

【摘要】：目的：将类胰岛素样生长因子1（Insulin-like growth factors-1, IGF-1）以明胶微球（Gelatinmicrosphere， GMs）为载体缓释剂，形成IGF-1明胶微球复合物，局部应用于兔下颌骨骨缺损处，通过对术后全身血清学及局部形态学和病理学变化的观察，研究IGF-1明胶微球复合物对下颌骨缺损愈合的影响。方法：将27只日本成年大耳白兔根据数字随机表法分成3组，各组均在下颌骨体部制作一大小为13mm×6mm×5mm的单侧皮质骨缺损模型，实验组于缺损区植入IGF-1明胶微球复合物，对照组植入吸附生理盐水的空白明胶微球，，空白对照组不做特殊处理。建模前后采耳缘静脉血，通过生化检查观察各组血液中钙、磷和碱性磷酸酶（Alkaline phosphatase,ALP）含量的动态变化；分别于术后4、8、12周每组各处死3只进行大体解剖观察、Ｘ线摄片、HE染色和新生骨小梁百分比测定。结果：建模成功，术后各组动物均未见明显的免疫排斥反应。大体标本观察显示：4周时各组都有新生组织生成，但都尚未充满缺损区，且与周围正常骨组织界限清楚，其中实验组探诊时质地稍硬，空白组及对照组探诊时质软。8周时，实验组新骨基本充满缺损区，色泽与周围骨组织基本一致，空白组与对照组可见暗红色骨质充满缺损内，与正常骨组织颜色略有差异。但各组仍可辨别缺损区与周围正常组织界限。12周时，各组骨缺损区基本被新生骨组织修复，颜色、质地与周围骨相近，边界不清。 X线片显示：4周时实验组缺损区边缘不均匀的高密度骨痂影呈云雾状分布，而对照组及空白组骨缺损区边缘密度及范围均明显低于实验组，8周时：各组骨缺损区密度均较4周时明显增高，其中实验组又高于对照组和空白组。12周：实验组骨密度与周围骨组织相近，对照组和空白组稍差，中间可见小范围低密度影。血清学显示：术后各组碱性磷酸酶值均升高，实验组峰值较对照组和空白组高（p0.05）且其出现时间较早，维持一段时间后逐渐降低，且随着缺损区骨修复的完成逐渐恢复到术前水平；术后2周时各组钙值均呈现升高趋势，实验组高于对照组（p0.05）,4周开始钙值逐渐降低，实验组下降较对照组显著（p0.05），到10周时趋于平稳，各组无明显差异，而与钙值相比，磷值呈现相反的趋势。病理染色显示：实验组骨缺损早期（4周）可见少量不成熟骨小梁和胶原成分形成；缺损8周时，各组均有大量新骨及类骨质形成，实验组不仅可见板层状成熟骨小梁均匀排列，且数量多于对照组；缺损12周时，实验组形成的新骨基本接近成熟，与正常骨质分界不明显。同时不论是4周、8周还是12周时，实验组骨密度及新生骨面积百分比都明显高于对照组和空白组，且差异有统计学意义，而对照组与空白组差异不明显。结论： 1、实验成功建立了兔下颌骨骨缺损模型。 2、血清ALP、钙值和磷值在不同时间段的差异性变化，可以反应各组不同时期缺损处的成骨情况，提示IGF-1/GMs复合物可能会促进颌骨缺损早期修复。 3、病理学及影像学结果也表明IGF-1/GMs复合物可能促进颌骨缺损早期修复，具有良好的生物相容性，为指导相关的临床研究提供了实验基础。
[Abstract]:Objective:
The insulin like growth factor 1 (Insulin-like growth factors-1, IGF-1) was used as the carrier release agent of Gelatinmicrosphere (Gelatinmicrosphere, GMs) as the carrier release agent to form the IGF-1 gelatin microsphere complex. It was applied locally to the rabbit mandible bone defect. By observing the changes of the whole body serology and the pathological changes of the local department after the operation, the microsphere of IGF-1 gelatin microsphere was studied. The effect of ball complex on the healing of mandibular defect.
Method:
27 adult Japanese white rabbits were divided into 3 groups according to the digital random table method. Each group made a unilateral cortical bone defect model of 13mm x 6mm x 5mm in the mandible body part. The experimental group implanted IGF-1 gelatin microsphere complex in the defect area, and the control group implanted blank gelatin microspheres adsorbed by the saline. The blank control group did not do special treatment. The dynamic changes of calcium, phosphorus and alkaline phosphatase (Alkaline phosphatase, ALP) content in the blood were observed by biochemical examination before and after the modeling, and 3 rats in each group were killed at 4,8,12 weeks after the operation for gross anatomical observation, X-ray photography, HE staining and the percentage of new bone trabecula.
Result:
After successful modeling, no obvious immunological rejection was observed in all animals after operation.
The gross specimen observation showed that there were new tissues in each group at 4 weeks, but all were not full of the defect area, and the boundary of normal bone tissue was clear. In the experimental group, the texture of the experimental group was slightly hard, the blank group and the control group were soft.8 weeks, the new bone in the experimental group was basically full of the loss area, the color and the color and the surrounding bone tissue were basically the same, blank group. In the control group, there was a slight difference between the dark red bone fill defect and the normal bone tissue color. However, the bone defect areas were basically repaired by the new bone tissue at.12 weeks, and the color and texture were close to the surrounding bone, and the boundary was not clear.
The X-ray showed that the density of high density callus in the edge of the defect area in the experimental group was cloudy and foggy at 4 weeks, while the margin density and range of the bone defect area in the control group and the blank group were significantly lower than that of the experimental group. At the 8 week, the density of the bone defects in each group was significantly higher than that of the 4 weeks, and the test group was higher than the control group and the blank group.12 weeks: the experiment was the experiment. The bone mineral density of the group was similar to that of the surrounding bone tissue, while the control group and the blank group were slightly worse.
Serology showed that the alkaline phosphatase of all groups increased after the operation, and the peak value of the experimental group was higher than that of the control group and the blank group (P0.05). It appeared earlier, and gradually decreased after a period of time, and gradually recovered to the preoperative level with the completion of bone repair in the defect area. The calcium values in each group were increased at 2 weeks after the operation, and the experimental group was higher than that in the experimental group. In group (P0.05), the value of calcium decreased gradually at the beginning of the 4 week, the decrease of the experimental group was significantly higher than that of the control group (P0.05), and it tended to be stable at the end of the 10 week, and there was no significant difference in each group, but the phosphorus value showed the opposite trend compared with the calcium value.
Pathological staining showed that a small amount of immature bone trabecula and collagen were formed in the early (4 weeks) bone defect of the experimental group, and a large number of new bone and osteoid were formed at 8 weeks of defect. The experimental group not only showed the lamellar matured trabecula in the experimental group, but also more than the control group. The new bone formed in the experimental group was almost close at 12 weeks, and the new bone formed basically close to the experimental group. At the same time, the percentage of bone mineral density and new bone area in the experimental group was significantly higher than that of the control group and the blank group at the same time of 4 weeks, 8 weeks or 12 weeks, and the difference was statistically significant, but the difference between the control group and the blank group was not obvious.
Conclusion:
1, a rabbit mandibular bone defect model was successfully established.
2, the difference of serum ALP, calcium and phosphorus in different time periods can reflect the osteogenesis of the defects at different stages, suggesting that the IGF-1/GMs complex may promote the early repair of the mandible defect.
3, the results of pathology and imaging also show that IGF-1/GMs complex may promote the early repair of jaw defect and have good biocompatibility, which provides an experimental basis for guiding the related clinical research.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R782.4

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