本文選題：類胰島素樣生長(zhǎng)因子1 + 明膠微球��； 參考：《山西醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的： 將類胰島素樣生長(zhǎng)因子1（Insulin-like growth factors-1, IGF-1）以明膠微球（Gelatinmicrosphere， GMs）為載體緩釋劑，形成IGF-1明膠微球復(fù)合物，局部應(yīng)用于兔下頜骨骨缺損處，通過(guò)對(duì)術(shù)后全身血清學(xué)及局部形態(tài)學(xué)和病理學(xué)變化的觀察，研究IGF-1明膠微球復(fù)合物對(duì)下頜骨缺損愈合的影響。 方法： 將27只日本成年大耳白兔根據(jù)數(shù)字隨機(jī)表法分成3組，各組均在下頜骨體部制作一大小為13mm×6mm×5mm的單側(cè)皮質(zhì)骨缺損模型，實(shí)驗(yàn)組于缺損區(qū)植入IGF-1明膠微球復(fù)合物，對(duì)照組植入吸附生理鹽水的空白明膠微球，，空白對(duì)照組不做特殊處理。建模前后采耳緣靜脈血，通過(guò)生化檢查觀察各組血液中鈣、磷和堿性磷酸酶（Alkaline phosphatase,ALP）含量的動(dòng)態(tài)變化；分別于術(shù)后4、8、12周每組各處死3只進(jìn)行大體解剖觀察、Ｘ線攝片、HE染色和新生骨小梁百分比測(cè)定。 結(jié)果： 建模成功，術(shù)后各組動(dòng)物均未見明顯的免疫排斥反應(yīng)。 大體標(biāo)本觀察顯示：4周時(shí)各組都有新生組織生成，但都尚未充滿缺損區(qū)，且與周圍正常骨組織界限清楚，其中實(shí)驗(yàn)組探診時(shí)質(zhì)地稍硬，空白組及對(duì)照組探診時(shí)質(zhì)軟。8周時(shí)，實(shí)驗(yàn)組新骨基本充滿缺損區(qū)，色澤與周圍骨組織基本一致，空白組與對(duì)照組可見暗紅色骨質(zhì)充滿缺損內(nèi)，與正常骨組織顏色略有差異。但各組仍可辨別缺損區(qū)與周圍正常組織界限。12周時(shí)，各組骨缺損區(qū)基本被新生骨組織修復(fù)，顏色、質(zhì)地與周圍骨相近，邊界不清。 X線片顯示：4周時(shí)實(shí)驗(yàn)組缺損區(qū)邊緣不均勻的高密度骨痂影呈云霧狀分布，而對(duì)照組及空白組骨缺損區(qū)邊緣密度及范圍均明顯低于實(shí)驗(yàn)組，8周時(shí)：各組骨缺損區(qū)密度均較4周時(shí)明顯增高，其中實(shí)驗(yàn)組又高于對(duì)照組和空白組。12周：實(shí)驗(yàn)組骨密度與周圍骨組織相近，對(duì)照組和空白組稍差，中間可見小范圍低密度影。 血清學(xué)顯示：術(shù)后各組堿性磷酸酶值均升高，實(shí)驗(yàn)組峰值較對(duì)照組和空白組高（p0.05）且其出現(xiàn)時(shí)間較早，維持一段時(shí)間后逐漸降低，且隨著缺損區(qū)骨修復(fù)的完成逐漸恢復(fù)到術(shù)前水平；術(shù)后2周時(shí)各組鈣值均呈現(xiàn)升高趨勢(shì)，實(shí)驗(yàn)組高于對(duì)照組（p0.05）,4周開始鈣值逐漸降低，實(shí)驗(yàn)組下降較對(duì)照組顯著（p0.05），到10周時(shí)趨于平穩(wěn)，各組無(wú)明顯差異，而與鈣值相比，磷值呈現(xiàn)相反的趨勢(shì)。 病理染色顯示：實(shí)驗(yàn)組骨缺損早期（4周）可見少量不成熟骨小梁和膠原成分形成；缺損8周時(shí)，各組均有大量新骨及類骨質(zhì)形成，實(shí)驗(yàn)組不僅可見板層狀成熟骨小梁均勻排列，且數(shù)量多于對(duì)照組；缺損12周時(shí)，實(shí)驗(yàn)組形成的新骨基本接近成熟，與正常骨質(zhì)分界不明顯。同時(shí)不論是4周、8周還是12周時(shí)，實(shí)驗(yàn)組骨密度及新生骨面積百分比都明顯高于對(duì)照組和空白組，且差異有統(tǒng)計(jì)學(xué)意義，而對(duì)照組與空白組差異不明顯。 結(jié)論： 1、實(shí)驗(yàn)成功建立了兔下頜骨骨缺損模型。 2、血清ALP、鈣值和磷值在不同時(shí)間段的差異性變化，可以反應(yīng)各組不同時(shí)期缺損處的成骨情況，提示IGF-1/GMs復(fù)合物可能會(huì)促進(jìn)頜骨缺損早期修復(fù)。 3、病理學(xué)及影像學(xué)結(jié)果也表明IGF-1/GMs復(fù)合物可能促進(jìn)頜骨缺損早期修復(fù)，具有良好的生物相容性，為指導(dǎo)相關(guān)的臨床研究提供了實(shí)驗(yàn)基礎(chǔ)。
[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.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R782.4

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