本文選題：大鼠 + 腦出血��； 參考：《鄭州大學》2014年碩士論文

【摘要】：研究背景 腦出血是臨床上常見的腦血管疾病，具有高致死率和高致殘率的特點，腦出血后出血損傷中心區(qū)域的神經(jīng)細胞死亡，進而導致相應(yīng)的神經(jīng)功能缺失，至今尚無真正有效的治療措施，目前移植具有自我更新和定向分化能力的外源性的多潛能干細胞是腦出血最具潛能的治療措施，骨髓單個核細胞因其具有提取容易、無需培養(yǎng)及可自體移植等諸多優(yōu)點，使之成為治療急性期腦出血的最佳種子細胞之一，最新研究證明靜脈移植BMMNCs安全有效，且能夠在特定的微環(huán)境的誘導下定向分化為多種細胞。 目的 探討骨髓單個核細胞（BMMNCs）移植治療對腦出血大鼠的膠質(zhì)源性神經(jīng)營養(yǎng)因子（GDNF）的表達、其腦內(nèi)神經(jīng)元樣細胞和星形膠質(zhì)樣細胞分化情況及神經(jīng)功能恢復的影響。 方法 紋狀體區(qū)立體定向注射膠原酶建立腦出血模型，篩選成功模型后隨機分為模型組（ICH組）和BMMNCs移植組（BMMNCs組），BMMNCs組于造模后24h后經(jīng)尾靜脈注入1mL含3×107個BMMNCs細胞懸液，分別于術(shù)后1d、7d、14d、28d采用改良的大鼠神經(jīng)功能評分（mNSS）觀察大鼠神經(jīng)行為學表現(xiàn)；于1d、7d、14d采用Western blotting方法檢測腦內(nèi)GDNF的表達情況；28d后采用免疫組織熒光雙標法示蹤BMMNCs腦內(nèi)分化情況。 結(jié)果 術(shù)后7d、14d、28d，BMMNCs組mNSS評分均明顯低于ICH組，差異有統(tǒng)計學意義（P0.05）；兩組的GDNF表達均于1d開始出現(xiàn)，7d達高峰，14d逐漸下降，ICH組各時間點GDNF的表達量均明顯低于BMMNCs組，差異有統(tǒng)計學意義（P0.05）；術(shù)后28d，，BMMNCs組紋狀體區(qū)可檢測到Brdu和NeuN雙標陽性細胞及Brdu和GFAP雙標陽性細胞。 結(jié)論 BMMNCs移植能顯著改善大鼠神經(jīng)行為學功能，顯著增加GDNF的分泌量，并能夠在腦出血大鼠體內(nèi)分化為神經(jīng)元樣細胞和星形膠質(zhì)樣細胞。
[Abstract]:Research background Intracerebral hemorrhage (ICH) is a common cerebrovascular disease with high mortality and high disability rate. So far, there is no effective treatment. Transplantation of exogenous pluripotent stem cells with self-renewal and directional differentiation is the most potential treatment for intracerebral hemorrhage, and bone marrow mononuclear cells are easy to extract because of their ability of self-renewal and directional differentiation. It is one of the best seed cells for the treatment of acute intracerebral hemorrhage without the advantages of culture and autologous transplantation. The latest research has proved that vein transplantation BMMNCs is safe and effective. And can be induced by specific microenvironment to differentiate into a variety of cells. Purpose To investigate the effects of bone marrow mononuclear cell transplantation (BMMNCs) on the expression of glial derived neurotrophic factor (GDNF) in rats with intracerebral hemorrhage (ICH), the differentiation of neuron-like cells and astrocytes in the brain and the recovery of neural function. Method The model of intracerebral hemorrhage was established by stereotactic injection of collagenase in the striatum. After screening, the model group was randomly divided into two groups: the model group (ICH group) and the BMMNCs transplantation group (BMMNCs group). After 24 hours, 1mL was injected into the caudal vein with 3 脳 107 BMMNCs cell suspensions. The neurobehavioral manifestations of rats were observed by modified rat neural function score (mNSSs) at 1 day, 7 days and 14 days after operation, and the expression of GDNF in brain was detected by Western blotting method on day 1 and day 7, respectively. After 28 days, the differentiation of BMMNCs in brain was traced by immunofluorescence double labeling method. Result The mNSS scores in the BMMNCs group were significantly lower than those in the ICH group (P 0.05), the GDNF expression in both groups began to appear on the 1st day and reached the peak on the 1st day and gradually decreased on the 14th day after operation. The expression of GDNF at all time points in the ICH group was significantly lower than that in the BMMNCs group. Brdu and NeuN double labeled positive cells and Brdu and GFAP double labeled positive cells could be detected in striatum of BMMNCs group 28 days after operation. Conclusion BMMNCs transplantation could significantly improve the neurobehavioral function of rats, increase the secretion of GDNF, and differentiate into neuron-like cells and astrocyte-like cells in rats with intracerebral hemorrhage.
【學位授予單位】：鄭州大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R743.34

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