本文選題：類胰島素樣生長因子I + 高原慢性低氧��； 參考：《蘇州大學(xué)》2015年碩士論文

【摘要】：類胰島素樣生長因子I(insulin-like growth factorⅠ,IGF-Ⅰ)是與胰島素高度同源的多肽類物質(zhì),主要由肝細(xì)胞合成和分泌。正常生理狀況下,機(jī)體組織器官在生長激素的調(diào)節(jié)下多能合成和分泌IGF-1,形成生長激素(Growth Hormone,GH)-類胰島素樣生長因子I軸(GH-IGF-I),作用于細(xì)胞表面IGF-1受體,參與組織的增殖或分化。同樣,GH-IGF-I影響骨骼的生長發(fā)育。GH濃度增高,促使循環(huán)系統(tǒng)及局部骨組織的IGF-1濃度增加,誘導(dǎo)維生素D活化,膠原及硫酸黏多糖合成,進(jìn)而介導(dǎo)GH促骨縱向生長的作用,然而缺乏IGF-1可以導(dǎo)致Laron綜合征(原發(fā)性生長激素不敏感綜合征),表現(xiàn)為人血清生長激素(Human Growth Hormone,HGH)水平正�；蚋摺GF-1等水平低下的家族性侏儒癥�？梢�,IFG-1在骨骼生長方面有著重要的影響。顱腦損傷合并骨折時(shí),機(jī)體為修復(fù)中樞神經(jīng)細(xì)胞的損傷,引發(fā)循環(huán)系統(tǒng)及局部組織區(qū)域的IGF-1應(yīng)激性增加,刺激骨膜下骨形成進(jìn)而促進(jìn)骨折加快愈合。缺氧作為一個(gè)獨(dú)立因素可調(diào)節(jié)機(jī)體IGF-I的表達(dá)。有研究表明慢性缺氧會(huì)抑制GH-IGF-I軸,提示環(huán)境低氧可能不利于骨折愈合。在臨床工作中,我們卻發(fā)現(xiàn)高原地區(qū)顱腦損傷后骨折愈合加速。因此在高原缺氧環(huán)境下,IGF-I水平受缺氧因素的影響,是否會(huì)引起骨折愈合速度加快?這成為我們思考的問題。據(jù)此,我們建立顱腦損傷合并骨折及單純性骨折的SD大鼠動(dòng)物模型,觀察在慢性低氧環(huán)境下SD大鼠顱腦損傷對(duì)血清、局部骨痂胰島素樣生長因子Ⅰ的表達(dá)及骨折愈合的影響。我們使用影像學(xué)診斷方法評(píng)估骨折愈合情況,采用Elisa法和免疫組化法檢測(cè)血清與骨痂局部胰島素樣生長因子Ⅰ的表達(dá)狀況,初步探討高原慢性缺氧環(huán)境下,顱腦損傷促進(jìn)骨折愈合的基本機(jī)制。實(shí)驗(yàn)結(jié)果如下:1.影像學(xué)檢測(cè)結(jié)果發(fā)現(xiàn)合并腦損傷的骨折愈合明顯好于單純骨折組,腦損傷合并組骨痂形成及改造提前,骨痂形成量明顯增多,骨折愈合加速。2.Elisa檢測(cè)結(jié)果表明血清不同組間比較,腦損合并骨折組血清IGF-I含量顯著高于其它組;單純腦損組血清IGF-I含量次之,高于單純骨折組;對(duì)照組、單純假腦損組、假腦損合并骨折組血清IGF-I含量之間無顯著差異。各組3,7,15,30天不同時(shí)間點(diǎn)之間血清IGF-I含量比較,發(fā)現(xiàn)單純腦損組、單純骨折組和腦損合并骨折組7天血清IGF-I含量升高,15天血清IGF-I含量達(dá)到高峰值,30天時(shí)有所下降。各時(shí)間點(diǎn)血清IGF-I含量存在顯著差異,對(duì)照組、單純假腦損組、假腦損合并骨折組不同時(shí)間點(diǎn)血清IGF-I含量之間無顯著差異。3.免疫組化檢測(cè)局部骨痂IGF-I含量,結(jié)果說明腦損合并骨折組骨痂局部IGF-I的表達(dá)明顯增加,15天腦損合并骨折組IGF-I陽性細(xì)胞數(shù)呈現(xiàn)高峰值,30天有所下降。結(jié)論:1.比較分析單純骨折組和顱腦損傷合并骨折組骨折愈合速度的差異性,發(fā)現(xiàn)顱腦損傷對(duì)合并骨折的愈合有促進(jìn)作用,其骨折愈合速度明顯快于單純骨折組。2.對(duì)照組、單純腦損假手術(shù)組、腦損合并骨折假手術(shù)組、單純腦損組、單純骨折組、腦損合并骨折組的血清IGF-I及骨折斷端IGF-I的表達(dá)存在差異性,提示腦損合并骨折組的IGF-I表達(dá)增高對(duì)骨修復(fù)愈合有十分重要的積極作用。綜上所述,高原慢性缺氧雖可抑制GH-IGF-I軸,但顱腦損傷合并骨折引發(fā)的IGF-I濃度增高,遠(yuǎn)遠(yuǎn)高于慢性缺氧對(duì)GH-IGF-I軸的抑制。故高原慢性缺氧條件下,借助于骨痂局部和血清中胰島素樣生長因子Ⅰ高表達(dá),顱腦損傷依然促進(jìn)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.

【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R651.15;R683

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本文編號(hào)：1731097