本文關(guān)鍵詞：IGF-1對全腦缺血大鼠認(rèn)知功能及p-Akt、p-mTOR蛋白的影響　出處：《川北醫(yī)學(xué)院》2015年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 全腦缺血 認(rèn)知障礙 IGF-1 p-Akt p-mTOR IGF-1受體阻斷劑

【摘要】：目的:探討外源性IGF-1對全腦缺血大鼠空間學(xué)習(xí)記憶能力及對p-Akt、p-m TOR蛋白的影響,進(jìn)而揭示IGF-1改善全腦缺血大鼠認(rèn)知障礙的可能機制。方法:將成年雄性Wistar大鼠隨機分成正常對照組、假手術(shù)組、模型組、IGF-1組、IGF-1+PPP組。對各手術(shù)組大鼠行側(cè)腦室置管術(shù),術(shù)后第6天,采用改良Pulsinelli四血管阻斷法(4-VO)復(fù)制全腦缺血模型,假手術(shù)組腹腔注射1ml DSMO(PPP溶媒),側(cè)腦室注射NS10ul;模型組腹腔注射1ml DSMO,側(cè)腦室注射NS10ul;IGF-1組腹腔注射1ml DSMO,側(cè)腦室注射IGF-1 10ul(0.2ug/ul);IGF-1+PPP組腹腔注射1ml PPP(20mg/kg,溶于1ml DSMO),側(cè)腦室注射IGF-1 10ul(0.2ug/ul),側(cè)腦室注射晚于腹腔注射30分鐘,連續(xù)注射7天。于分組前、藥物處理7天后分別對各組大鼠行Morris水迷宮實驗,水迷宮實驗包括定位航行試驗和空間探索實驗;HE染色觀察各組大鼠海馬CA1區(qū)椎體細(xì)胞形態(tài)變化;免疫組化法檢測各組大鼠海馬CA1區(qū)p-Akt、p-m TOR蛋白的表達(dá)情況,采用Image Pro Plus 6.0軟件處理免疫組化圖片,統(tǒng)計IOD值,結(jié)果用SPSS17.0統(tǒng)計軟件進(jìn)行統(tǒng)計學(xué)處理。結(jié)果:1)Morris水迷宮實驗結(jié)果:藥物處理7天后,模型組大鼠全時程平均逃避潛伏期較正常組及假手術(shù)組延長(p0.05),IGF-1組大鼠全時程平均逃避潛伏期較模型組縮短(p0.05),IGF-1+PPP組大鼠全時程平均逃避潛伏期較IGF-1組延長(p0.05);模型組大鼠跨越原平臺次數(shù)較正常組及假手術(shù)組減少(p0.05),IGF-1組大鼠跨越原平臺次數(shù)較模型組增多(p0.05),IGF-1+PPP組大鼠跨越原平臺次數(shù)較IGF-1組減少(p0.05);模型組大鼠在原平臺象限游泳時間較正常組及假手術(shù)組減少(p0.05),IGF-1組大鼠在原平臺象限游泳時間較模型組增多(p0.05),IGF-1+PPP組大鼠在原平臺象限游泳時間較IGF-1組減少(p0.05)。2)HE染色結(jié)果:模型組海馬CA1區(qū)細(xì)胞較正常組及假手術(shù)組排列紊亂,細(xì)胞稀疏,細(xì)胞核不規(guī)則;IGF-1組海馬CA1區(qū)細(xì)胞較模型組排列整齊,結(jié)構(gòu)較清晰,不規(guī)則細(xì)胞減少。IGF-1+PPP組海馬CA1區(qū)細(xì)胞較IGF-1組排列紊亂,細(xì)胞稀疏,細(xì)胞核不規(guī)則,可見核固縮。3)免疫組化結(jié)果:各組均可見p-Akt、p-m TOR陽性表達(dá)。模型組海馬CA1區(qū)陽性表達(dá)較正常組及假手術(shù)組增多(p0.05);IGF-1組海馬CA1區(qū)陽性表達(dá)較模型組增多(p0.05);IGF-1+PPP組海馬CA1區(qū)陽性表達(dá)較IGF-1組減少(p0.05);模型組及IGF-1+PPP組p-Akt、p-m TOR蛋白陽性表達(dá)差異沒有統(tǒng)計學(xué)意義。結(jié)論:1)外源性IGF-1能夠改善全腦缺血大鼠空間學(xué)習(xí)記憶能力。2)外源性IGF-1能夠增加全腦缺血大鼠海馬CA1區(qū)p-Akt、p-m TOR蛋白的表達(dá)水平;加用IGF-1受體阻斷劑PPP后全腦缺血大鼠海馬CA1區(qū)p-Akt、p-m TOR蛋白的表達(dá)水平較IGF-1組減少。提示IGF-1可能通過促進(jìn)p-Akt及p-m TOR蛋白的表達(dá),從而改善全腦缺血大鼠空間學(xué)習(xí)記憶能力。
[Abstract]:Objective: To investigate the effects of exogenous IGF-1 on rat spatial learning and memory ability and cerebral ischemia on p-Akt, P-M TOR protein, and reveal the possible mechanism of IGF-1 in ameliorating cognitive impairment in rats with cerebral ischemia. Methods: adult male Wistar rats were randomly divided into normal control group, sham operation group, model group, IGF-1 group, IGF-1+PPP group. The operation group rats underwent lateral ventricle catheterization, sixth days after operation, by using modified Pulsinelli method four vessels (4-VO) copy the model of whole brain ischemia in sham operation group, intraperitoneal injection of 1ml DSMO (PPP solvent), intracerebroventricular injection of NS10ul; model by intraperitoneal injection of 1ml DSMO, lateral ventricle NS10ul injection; group IGF-1 intraperitoneal injection of 1ml DSMO, intracerebroventricular injection of IGF-1 (0.2ug/ul 10ul); IGF-1+PPP group received intraperitoneal injection of 1ml PPP (20mg/kg, dissolved in 1ml DSMO), intracerebroventricular injection of IGF-1 10ul (0.2ug/ul), 30 minutes after intracerebroventricular injection of intraperitoneal injection, continuous injection of 7 days. Before the group, after treatment for 7 days respectively group of rats by Morris water maze test, positioning navigation test and spatial probe test including water maze test; morphological observation of hippocampal CA1 pyramidal cells in rats with HE staining; immunohistochemistry p-Akt in hippocampal CA1 region of rats, the expression of P-M TOR protein. Using Image Pro Plus 6 software with immunohistochemical images, the statistical value of IOD results with SPSS17.0 statistical software. Results: 1) Morris water maze test results: after treatment for 7 days, the rats in the model group were all Cheng Ping latency than the normal group and sham operation group (P0.05 group), IGF-1 extension rat time average escape latency shortened than that in the model group (P0.05), IGF-1+PPP group rats all duration the average escape latency longer than that of group IGF-1 (P0.05); the rats in the model group compared with the number of times of crossing platform in normal group and sham operation group Reduce (P0.05), IGF-1 group of rats crossing platform times more than model group (P0.05), IGF-1+PPP group of rats crossing platform times lower than that of the IGF-1 group (P0.05); the rats in the model group decreased in the original platform quadrant swimming time than the normal group and sham operation group (P0.05), the rats of group IGF-1 increased in the original platform quadrant swimming time compared to the model group (P0.05), the rats of group IGF-1+PPP decreased in the original platform quadrant swimming time than group IGF-1 (P0.05).2) HE staining: model group hippocampus CA1 cells than in normal group and sham operation group were disordered, sparse, irregular nuclei; IGF-1 group in hippocampus CA1 area compared with the model group, cells arranged orderly, clear structure, irregular cells decreased hippocampal CA1 neurons in.IGF-1+PPP group than in IGF-1 group cells arranged in disorder, sparse, irregular nuclei karyopyknosis.3) immunohistochemical results: each group can see p-Akt, P-M positive expression of TOR in model group sea. The positive expression of horse CA1 area than in normal group and sham operation group (P0.05); the positive expression of IGF-1 group in hippocampus CA1 region increased in comparison with the model group (P0.05 group); the positive expression of IGF-1+PPP in hippocampal CA1 region was lower than IGF-1 group (P0.05); model group and IGF-1+PPP group p-Akt, P-M TOR protein positive expression difference was not statistically significant conclusion: 1) exogenous IGF-1 can improve the ability of learning and memory of.2 space in rats with global cerebral ischemia) exogenous IGF-1 could increase the cerebral ischemia in rats hippocampus CA1 p-Akt, expression of P-M TOR protein; with IGF-1 receptor antagonist PPP after cerebral ischemia p-Akt CA1 of rat hippocampus, the expression level of P-M TOR protein was lower than IGF-1 group. IGF-1 can promote the expression of p-Akt and P-M TOR protein, so as to improve the spatial learning and memory abilities in rats with global cerebral ischemia.

【學(xué)位授予單位】：川北醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R749.13

【參考文獻(xiàn)】

相關(guān)期刊論文 前4條

1 高東;周中和;;實驗性血管性癡呆的模型制作問題[J];國外醫(yī)學(xué)(老年醫(yī)學(xué)分冊);2002年02期

2 王立峻;劉建勛;張繼紅;鐘志強;鄧丹;宮旭海;李雪松;;血管性認(rèn)知障礙研究現(xiàn)狀[J];中國傷殘醫(yī)學(xué);2012年04期

3 陳翔;高風(fēng)超;田新英;;血管性癡呆動物模型的研究現(xiàn)狀[J];醫(yī)學(xué)綜述;2013年13期

4 宮秀群;馬敏敏;徐格林;;IGF-1在血管性癡呆中的作用[J];中風(fēng)與神經(jīng)疾病雜志;2011年06期

相關(guān)博士學(xué)位論文 前1條

1 石廣濱;胰島素樣生長因子-1對癡呆模型大鼠保護(hù)作用及其機制的實驗研究[D];吉林大學(xué);2006年

，

本文編號：1415026