低氧大鼠颅脑损伤合并骨折后IGF-I表达变化的生物学意义

发布时间：2018-04-10 11:56

本文选题：类胰岛素样生长因子I + 高原慢性低氧　；参考：《苏州大学》2015年硕士论文

【摘要】：类胰岛素样生长因子I(insulin-like growth factorⅠ,IGF-Ⅰ)是与胰岛素高度同源的多肽类物质,主要由肝细胞合成和分泌。正常生理状况下,机体组织器官在生长激素的调节下多能合成和分泌IGF-1,形成生长激素(Growth Hormone,GH)-类胰岛素样生长因子I轴(GH-IGF-I),作用于细胞表面IGF-1受体,参与组织的增殖或分化。同样,GH-IGF-I影响骨骼的生长发育。GH浓度增高,促使循环系统及局部骨组织的IGF-1浓度增加,诱导维生素D活化,胶原及硫酸黏多糖合成,进而介导GH促骨纵向生长的作用,然而缺乏IGF-1可以导致Laron综合征(原发性生长激素不敏感综合征),表现为人血清生长激素(Human Growth Hormone,HGH)水平正常或高、IGF-1等水平低下的家族性侏儒症。可见,IFG-1在骨骼生长方面有着重要的影响。颅脑损伤合并骨折时,机体为修复中枢神经细胞的损伤,引发循环系统及局部组织区域的IGF-1应激性增加,刺激骨膜下骨形成进而促进骨折加快愈合。缺氧作为一个独立因素可调节机体IGF-I的表达。有研究表明慢性缺氧会抑制GH-IGF-I轴,提示环境低氧可能不利于骨折愈合。在临床工作中,我们却发现高原地区颅脑损伤后骨折愈合加速。因此在高原缺氧环境下,IGF-I水平受缺氧因素的影响,是否会引起骨折愈合速度加快?这成为我们思考的问题。据此,我们建立颅脑损伤合并骨折及单纯性骨折的SD大鼠动物模型,观察在慢性低氧环境下SD大鼠颅脑损伤对血清、局部骨痂胰岛素样生长因子Ⅰ的表达及骨折愈合的影响。我们使用影像学诊断方法评估骨折愈合情况,采用Elisa法和免疫组化法检测血清与骨痂局部胰岛素样生长因子Ⅰ的表达状况,初步探讨高原慢性缺氧环境下,颅脑损伤促进骨折愈合的基本机制。实验结果如下:1.影像学检测结果发现合并脑损伤的骨折愈合明显好于单纯骨折组,脑损伤合并组骨痂形成及改造提前,骨痂形成量明显增多,骨折愈合加速。2.Elisa检测结果表明血清不同组间比较,脑损合并骨折组血清IGF-I含量显著高于其它组;单纯脑损组血清IGF-I含量次之,高于单纯骨折组;对照组、单纯假脑损组、假脑损合并骨折组血清IGF-I含量之间无显著差异。各组3,7,15,30天不同时间点之间血清IGF-I含量比较,发现单纯脑损组、单纯骨折组和脑损合并骨折组7天血清IGF-I含量升高,15天血清IGF-I含量达到高峰值,30天时有所下降。各时间点血清IGF-I含量存在显著差异,对照组、单纯假脑损组、假脑损合并骨折组不同时间点血清IGF-I含量之间无显著差异。3.免疫组化检测局部骨痂IGF-I含量,结果说明脑损合并骨折组骨痂局部IGF-I的表达明显增加,15天脑损合并骨折组IGF-I阳性细胞数呈现高峰值,30天有所下降。结论:1.比较分析单纯骨折组和颅脑损伤合并骨折组骨折愈合速度的差异性,发现颅脑损伤对合并骨折的愈合有促进作用,其骨折愈合速度明显快于单纯骨折组。2.对照组、单纯脑损假手术组、脑损合并骨折假手术组、单纯脑损组、单纯骨折组、脑损合并骨折组的血清IGF-I及骨折断端IGF-I的表达存在差异性,提示脑损合并骨折组的IGF-I表达增高对骨修复愈合有十分重要的积极作用。综上所述,高原慢性缺氧虽可抑制GH-IGF-I轴,但颅脑损伤合并骨折引发的IGF-I浓度增高,远远高于慢性缺氧对GH-IGF-I轴的抑制。故高原慢性缺氧条件下,借助于骨痂局部和血清中胰岛素样生长因子Ⅰ高表达,颅脑损伤依然促进骨折愈合加速。
[Abstract]:Insulin-like growth factor I (insulin-like growth, factor I, IGF- I) is a polypeptide highly homologous with insulin, synthesized mainly by hepatocytes and secreted. Under normal physiological condition, the body tissues and organs in the regulation of growth hormone synthesis and secretion of more than IGF-1, the formation of growth hormone (Growth Hormone, GH) - insulin-like growth factor I (GH-IGF-I), acting on the axis of cell surface IGF-1 receptors, participate in tissue proliferation or differentiation. Similarly, GH-IGF-I influence the growth and development of bone.GH concentration, increase the circulatory system and local bone tissue IGF-1 concentration induced by vitamin D activation, collagen and sulfate proteoglycan synthesis, and GH mediated bone longitudinal growth, but the lack of IGF-1 can cause Laron syndrome (primary growth hormone insensitivity syndrome), expression of human serum growth hormone (Human Growth, Hormone, HGH) level of normal Low or high IGF-1 level of familial dwarfism. Therefore, IFG-1 plays an important role in bone growth. Brain injury associated with fracture, the body for the repair of cells of the central nervous system injury caused by IGF-1 stress, circulatory system and local tissue region increased, stimulation of subperiosteal bone formation and accelerate fracture healing the expression of hypoxia. As an independent factor can regulate the body's IGF-I. Studies have shown that chronic hypoxia could inhibit the GH-IGF-I axis, suggesting that hypoxia environment may not be conducive to fracture healing. In clinical work, we found that the plateau area after craniocerebral injury accelerated fracture healing. So in the environment of the plateau, the IGF-I level is affected by hypoxia factors and whether it will lead to accelerated fracture healing? This has become our problems. Accordingly, we establish animal model of craniocerebral injury complicated with fracture and simple fracture of SD rats In the observation, under chronic hypoxia environment SD rat brain injury on serum expression of local bone callus, insulin-like growth factor and fracture healing. We used imaging diagnostic methods for assessment of fracture healing by Elisa method and immunohistochemistry were used to detect serum and bone local insulin-like growth factor expression in preliminary study of chronic hypobaric hypoxia environment, the basic mechanism of promoting fracture healing of traumatic brain injury. The experimental results are as follows: 1.. The imaging detection results with brain injury healing was significantly better than simple fracture group, brain injury group the callus formation and transformation in advance, callus formation was significantly increased, healing.2.Elisa detection the results showed that different group comparison between fractures, brain damage and fracture of serum levels of IGF-I were significantly higher than that of other groups; simple brain damage group serum IGF-I content, higher than simple fracture group The control group, only sham; brain damage group, sham brain damage fracture with no significant difference between the serum content of IGF-I group. Comparison between groups 3,7,15,30 days at different time points of the content of IGF-I in serum, found simple brain damage group, fracture group and brain damage associated with fracture group 7 days increased the content of serum IGF-I, serum IGF-I content reached 15 days high peak, 30 days decreased. There was significant difference, the content of IGF-I in serum in the control group, only sham brain damage group, sham brain damage fracture with no significant difference.3. immunohistochemical detection of local bone callus IGF-I content between the serum content of IGF-I group at different time points. The results indicated that expression of brain damage complicated with bone fracture group at the local IGF-I increased significantly in 15 days, brain damage and fracture group the number of IGF-I positive cells showed a high peak, 30 days decreased. Conclusion: 1. compare the fracture group and fracture group of craniocerebral injury combined with fracture healing. , found that brain injury can promote the healing of fracture, the fracture healing rate was faster than the simple fracture group.2. control group, sham operation group, simple brain damage, brain damage, fracture and the sham operation group, cerebral injury group, fracture group, differences in expression of brain damage associated with fracture group serum IGF-I and the broken end of the fracture of IGF-I, suggesting that brain damage associated with fracture group increased expression of IGF-I on bone healing have very important positive role. To sum up, the high altitude hypoxia can inhibit the GH-IGF-I axis, but the fracture with brain injury caused by the concentration of IGF-I is much higher than that of chronic hypoxia increased, the inhibition of GH-IGF-I axis. Therefore, chronic hypobaric hypoxia under the condition, with the help of local bone callus and serum insulin-like growth factor expression, brain injury still promote accelerated fracture healing.

【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R651.15;R683

【参考文献】