發(fā)布時(shí)間：2018-03-17 10:19

  本文選題：糖耐量受損　切入點(diǎn)：炎癥反應(yīng)　出處：《天津醫(yī)科大學(xué)》2014年碩士論文　論文類(lèi)型：學(xué)位論文

【摘要】：目的 本研究通過(guò)建立糖耐量受損大鼠模型,檢測(cè)不同時(shí)間點(diǎn)大鼠認(rèn)知功能情況,并檢測(cè)不同時(shí)間點(diǎn)大鼠腦組織炎性通路中關(guān)鍵因子的表達(dá)情況,分析大鼠認(rèn)知功能與炎性因子表達(dá)的關(guān)系,以求進(jìn)一步探討糖耐量受損對(duì)大鼠認(rèn)知功能的影響,及其相關(guān)機(jī)制,為指導(dǎo)臨床工作提供理論依據(jù)。 方法 選取新生Wistar大鼠80只(體重180-220g)。隨機(jī)分為實(shí)驗(yàn)組和對(duì)照組,每組大鼠40只,實(shí)驗(yàn)組為糖耐量受損模型組,用高脂高糖飼料喂養(yǎng),實(shí)驗(yàn)動(dòng)物及飼料由天津醫(yī)科大學(xué)動(dòng)物實(shí)驗(yàn)中心提供。5周后測(cè)定大鼠血糖情況,并分別于第5周,10周,15周,20周采用水迷宮方法評(píng)定大鼠認(rèn)知情況,采用免疫組化和原位雜交技術(shù)測(cè)定大鼠腦組織核轉(zhuǎn)錄因子(factor-kappa B, NF-κB),白細(xì)胞介素-1β (interleukin-1β, IL-1β)水平。對(duì)照組,普通飼料喂養(yǎng),分別于第5周,10周,15周,20周,進(jìn)行認(rèn)知功能評(píng)定和測(cè)定炎性因子表達(dá)水平。 結(jié)果 水迷宮實(shí)驗(yàn)：實(shí)驗(yàn)組大鼠在實(shí)驗(yàn)初期學(xué)習(xí)及記憶能力較對(duì)照組無(wú)顯著差異,隨著飼養(yǎng)時(shí)間的延長(zhǎng),實(shí)驗(yàn)組大鼠逐漸成模,于飼養(yǎng)第15周全部成模,之后反復(fù)監(jiān)測(cè)大鼠認(rèn)知功能提示實(shí)驗(yàn)組大鼠與對(duì)照組相比學(xué)習(xí)及記憶能力減退,于第15周后有顯著差異(P0.05)。 HE染色：與對(duì)照組相比,實(shí)驗(yàn)組光鏡下偶可見(jiàn)凋亡細(xì)胞,胞漿紅染,細(xì)胞核染色質(zhì)聚集成團(tuán)塊狀,由于凋亡細(xì)胞迅速被吞噬,又無(wú)炎癥反應(yīng),因此在常規(guī)切片檢查時(shí)一般不易發(fā)現(xiàn)。 NF-κB的免疫組化和原位雜交測(cè)定：與對(duì)照組比較,糖耐量受損大鼠造模成功后NF-κB的陽(yáng)性表達(dá)增多,于15周后差異有統(tǒng)計(jì)學(xué)意義(P0.05),于20周后有顯著差異(P0.01)。 IL-1β的免疫組化和原位雜交測(cè)定：與對(duì)照組比較,糖耐量受損大鼠造模成功后IL-1β的陽(yáng)性表達(dá)增多,于15周后差異有統(tǒng)計(jì)學(xué)意義(P0.05),于20周后有顯著差異(P0.01)。 相關(guān)性分析：通過(guò)Pearson直線相關(guān)回歸分析發(fā)現(xiàn),實(shí)驗(yàn)組大鼠學(xué)習(xí)記憶成績(jī)與NF-κB、IL-1β陽(yáng)性表達(dá)水平呈負(fù)相關(guān),結(jié)果有統(tǒng)計(jì)學(xué)意義(P0.05)。說(shuō)明NF-κB、IL-1β表達(dá)水平變化與認(rèn)知障礙有相關(guān)性。 結(jié)論 通過(guò)水迷宮實(shí)驗(yàn)、免疫組化、原位雜交實(shí)驗(yàn)等研究,顯示糖耐量受損對(duì)大鼠認(rèn)知障礙的發(fā)生有顯著影響,其發(fā)病機(jī)制可能與大鼠腦組織中神經(jīng)細(xì)胞炎性因子NF-κB、IL-1β的表達(dá)增強(qiáng)有關(guān)。
[Abstract]:Purpose. In this study, the rat model of impaired glucose tolerance was established to detect the cognitive function of rats at different time points and the expression of key factors in inflammatory pathway of rat brain at different time points. The relationship between cognitive function and the expression of inflammatory factors in rats was analyzed in order to further explore the effects of impaired glucose tolerance on cognitive function and its related mechanisms in order to provide theoretical basis for guiding clinical work. Method. Eighty newborn Wistar rats (body weight 180-220 g) were randomly divided into experimental group and control group with 40 rats in each group. The experimental group was treated with high fat and high sugar diet. Experimental animals and feed were provided by the Animal experiment Center of Tianjin Medical University for blood glucose determination after 5 weeks. The cognition of rats was assessed by water maze method at 5 weeks, 10 weeks, 15 weeks, and 20 weeks, respectively. The levels of factor-kappa B, NF- 魏 B, interleukin-1 尾 -interleukin-1 尾, IL-1 尾 in rat brain were determined by immunohistochemistry and in situ hybridization. The cognitive function was assessed and the expression of inflammatory factors was measured. Results. Water maze test: there was no significant difference in learning and memory ability between the experimental group and the control group at the beginning of the experiment. With the prolongation of the feeding time, the rats of the experimental group gradually became models, and all of the rats in the experimental group became models at the 15th week of feeding. After repeated monitoring of the cognitive function of the experimental group compared with the control group, the learning and memory abilities of the experimental group were decreased, and there was a significant difference after 15 weeks (P 0.05). HE staining: compared with the control group, apoptosis cells were occasionally seen in the experimental group under light microscope, cytoplasmic red staining, nuclear chromatin aggregation into a mass, because the apoptotic cells were quickly swallowed up, and there was no inflammatory reaction. Therefore, it is not easy to find in the routine section examination. Immunohistochemistry and in situ hybridization of NF- 魏 B: compared with the control group, the positive expression of NF- 魏 B was increased in the model of impaired glucose tolerance rats, which was significantly different after 15 weeks and 20 weeks later. Immunohistochemical and in situ hybridization of IL-1 尾: compared with the control group, the positive expression of IL-1 尾 increased after successful modeling in impaired glucose tolerance rats. The difference was statistically significant after 15 weeks, and significantly different after 20 weeks. Correlation analysis: by Pearson linear correlation regression analysis, it was found that there was a negative correlation between the learning and memory achievement and the positive expression of NF- 魏 B, IL-1 尾 in the experimental group, the results showed that there was a significant correlation between the expression of IL-1 尾 and cognitive impairment in the experimental group (P 0.05). Conclusion. The results of water maze test, immunohistochemistry and in situ hybridization showed that impaired glucose tolerance had a significant effect on the occurrence of cognitive impairment in rats. The pathogenesis may be related to the increased expression of neuroinflammatory factor NF- 魏 B and IL-1 尾 in rat brain.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R749.24

【參考文獻(xiàn)】

相關(guān)期刊論文 前9條

1 張定榮;張海鴻;車(chē)芬芳;徐書(shū)珍;;新生鼠腦組織缺氧缺血再灌注損傷NF-κB的表達(dá)及意義[J];濱州醫(yī)學(xué)院學(xué)報(bào);2009年04期

2 蔡志友;晏勇;吳芳;李潔穎;;小膠質(zhì)細(xì)胞與阿爾茨海默病神經(jīng)炎癥[J];重慶醫(yī)學(xué);2008年07期

3 梁慶成,梁松嵐,陳立杰;NF-κB在腦缺血再灌注損傷中的雙重作用[J];哈爾濱醫(yī)科大學(xué)學(xué)報(bào);2005年01期

4 肖醉萱;鄧德明;孫愛(ài)萍;;NF-κB、PKC與糖尿病及胰島素的抗炎作用[J];長(zhǎng)江大學(xué)學(xué)報(bào)(自然科學(xué)版)醫(yī)學(xué)卷;2010年01期

5 張勁松,王興宇,單佑安,張宗梁;轉(zhuǎn)錄因子NF-κB的研究進(jìn)展[J];科學(xué)通報(bào);2002年05期

6 向靜;王寧;阿布力克木·吐?tīng)柕?;核因子-κB信號(hào)通路的研究進(jìn)展[J];新疆醫(yī)科大學(xué)學(xué)報(bào);2011年01期

7 邢飛躍,趙克森,姜勇;NF-κB的信號(hào)通路與阻斷策略[J];中國(guó)病理生理雜志;2003年06期

8 冷錦紅;于世家;;糖尿病與NF-κB信號(hào)轉(zhuǎn)導(dǎo)通路[J];中華中醫(yī)藥學(xué)刊;2008年06期

9 鮑麗彥;余劍;;首發(fā)腦梗死患者發(fā)生認(rèn)知功能障礙的影響因素研究[J];中國(guó)現(xiàn)代醫(yī)生;2013年18期

，

本文編號(hào)：1624304