本文關(guān)鍵詞： TLR2 腦白質(zhì)脫髓鞘 慢性腦缺血 少突膠質(zhì)前體細(xì)胞 少突膠質(zhì)細(xì)胞　出處：《西南醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:研究TLR2蛋白在慢性缺血性腦白質(zhì)脫髓鞘病變中的表達(dá)情況及探討TLR2蛋白是否參與缺血性腦白質(zhì)脫髓鞘病變及可能的參與機(jī)制。方法:將16只成年比格犬按照隨機(jī)化原則分為假手術(shù)組(A組)和實(shí)驗(yàn)組,其中實(shí)驗(yàn)組使用血管結(jié)扎法制作成比格犬腦缺血?jiǎng)用}模型,依據(jù)腦缺血輕中重不同程度分為B組、C組、D組。選取實(shí)驗(yàn)動物雙側(cè)側(cè)腦室邊緣部位腦白質(zhì)作為檢測標(biāo)本,采用HE染色和LFB染色法分別觀察各組腦白質(zhì)的病理變化和標(biāo)準(zhǔn)化評分后比較各組腦白質(zhì)脫髓鞘病變程度。使用免疫組化方法檢測標(biāo)本中TLR2、NG2、CNPase表達(dá)水平情況。采用Spearman秩相關(guān)分析法分析TLR2與CNPase之間的相關(guān)性。結(jié)果:(1)HE染色中假手術(shù)組腦白質(zhì)染色均勻,細(xì)胞形態(tài)正常,無脫髓鞘改變;實(shí)驗(yàn)B、C、D組可見不同程度的神經(jīng)纖維排列紊亂,細(xì)胞腫脹、核固縮。LFB染色后可見假手術(shù)組髓鞘形態(tài)正常,染色均勻;實(shí)驗(yàn)組見明顯脫髓鞘改變:B組腦白質(zhì)脫髓鞘病變相對較輕,表現(xiàn)髓鞘形態(tài)紊亂,染色不均;C組可見髓鞘腫脹、斷裂,有明顯的液泡形成;D組腦白質(zhì)脫髓鞘病變最為嚴(yán)重,可見有髓纖維消失,脂質(zhì)空泡形成,不顯色。(2)采用Hideaki標(biāo)準(zhǔn)化評分評估脫髓鞘病變程度。其中假手術(shù)組為0.63±0.52分值最低,其次實(shí)驗(yàn)B組的分值為1.25±0.46和實(shí)驗(yàn)C組的分值為1.63±0.52,實(shí)驗(yàn)組D為1.88±0.64分值最高。假手術(shù)組與實(shí)驗(yàn)B組、C組和D組比較差異均具有統(tǒng)計(jì)學(xué)意義(P0.05)。(3)免疫組化檢測顯示:1)TLR2蛋白表達(dá)水平情況:在假手術(shù)組為0.148±0.058表達(dá)水平最低,而實(shí)驗(yàn)B組為0.185±0.023、實(shí)驗(yàn)C組為0.185±0.025和實(shí)驗(yàn)D組為0.191±0.016表達(dá)水平最高。與假手術(shù)組相比,實(shí)驗(yàn)B、C、D組TLR2蛋白表達(dá)水平明顯增高且兩者比較差異具有統(tǒng)計(jì)學(xué)意義(P0.05)。2)NG2表達(dá)情況:在假手術(shù)組為0.147±0.021表達(dá)水平最低,在實(shí)驗(yàn)B組為0.169±0.017,實(shí)驗(yàn)C組為0.170±0.016、實(shí)驗(yàn)D組為0.177±0.018表達(dá)水平最高。實(shí)驗(yàn)B、C、D組與假手術(shù)組相比,NG2表達(dá)水平增高,兩者比較具有統(tǒng)計(jì)學(xué)差異P0.05)。3)CNPase表達(dá)水平情況:在假手術(shù)組中CNPase的表達(dá)水平為0.287±0.032最高,而在實(shí)驗(yàn)D組為0.213±0.015表達(dá)水平最低,其他在實(shí)驗(yàn)B、C組中CNPase的表達(dá)水平分別為0.225±0.025和0.222±0.026。與假手術(shù)組相比,實(shí)驗(yàn)B、C、D組CNPase表達(dá)水平有所降低,兩者比較差異具有統(tǒng)計(jì)學(xué)意義(P0.05)。(4)通過對TLR2與CNPase的表達(dá)情況進(jìn)行Spearman秩相關(guān)性分析結(jié)果顯示:TLR2與CNPase的表達(dá)水平成負(fù)相關(guān)(r=-0.382,P0.01)。結(jié)論TLR2蛋白參與了慢性缺血性腦白質(zhì)脫髓鞘病變,推測機(jī)制可能是TLR2蛋白的表達(dá)水平上調(diào)一方面引起CNPase蛋白表達(dá)水平下調(diào),少突膠質(zhì)細(xì)胞的減少;另一方面阻礙少突膠質(zhì)前體細(xì)胞分化成熟從而影響髓鞘再生引起脫髓鞘病變。
[Abstract]:Objective: to study the expression of TLR2 protein in chronic ischemic white matter demyelinating lesions and to explore whether TLR2 protein is involved in ischemic white matter demyelinating lesions and its possible mechanism. Sixteen adult Beagle dogs were randomly divided into sham-operated group (. Group A) and experimental group. The experimental group was made into the model of cerebral ischemia artery by vascular ligation. According to the light, moderate and heavy cerebral ischemia, the experimental group was divided into group B and C. Group D: the white matter of bilateral ventricular margin was selected as the test specimen. The pathological changes and standardized scores of white matter in each group were observed by HE staining and LFB staining respectively. The degree of demyelinating lesions in white matter of each group was compared. The TLR2 in the samples was detected by immunohistochemical method. NG2. CNPase expression level. Spearman rank correlation analysis was used to analyze the correlation between TLR2 and CNPase. In HE staining, white matter staining was uniform in sham-operation group. The morphology of the cells was normal and no demyelinating changes were observed. The nerve fibers were disordered, the cells were swollen, and the myelin sheath in the sham operation group was normal and even after the pyknosis. LFB staining. In the experimental group, obvious demyelinating changes were observed in the white matter of brain in group B, the lesions were relatively light, and the morphology of myelin was disordered and the staining was uneven. In group C, myelin swelling, rupture and vacuole formation were observed. In group D, the lesions of white matter demyelination were the most serious, myelinated fibers disappeared and lipid vacuoles were formed. The degree of demyelinating lesions was evaluated by Hideaki standard score, and the lowest score was 0.63 鹵0.52 in the sham operation group. Secondly, the score of group B was 1.25 鹵0.46 and that of group C was 1.63 鹵0.52, and that of group D was 1.88 鹵0.64. The difference between group C and group D was statistically significant (P0.05, P < 0.05). The expression of TLR2 protein was the lowest in sham-operated group (0.148 鹵0.058). The highest expression level was found in group B (0.185 鹵0.023), group C (0.185 鹵0.025) and group D (0.191 鹵0.016). C. The expression of TLR2 protein in group D was significantly increased and the difference was statistically significant (P 0.05. 2). The expression of NG2 was the lowest in sham-operated group (0.147 鹵0.021). The highest expression level was found in group B (0.169 鹵0.017), group C (0.170 鹵0.016) and group D (0.177 鹵0.018). Compared with sham operation group, the expression of NG2 in group D was higher than that in group D. There was statistical difference between the two groups in the expression of CNPase: the expression level of CNPase was the highest in sham-operated group (0.287 鹵0.032). The lowest level of expression was 0.213 鹵0.015 in group D, and the other was in experiment B. The expression levels of CNPase in group C were 0.225 鹵0.025 and 0.222 鹵0.026, respectively. The expression of CNPase in group D was decreased. The difference between the two is statistically significant (P0.05. 4). The results of Spearman rank correlation analysis on the expression of TLR2 and CNPase showed that there was a negative correlation between the expression level of CNPase and the expression level of CNPase. Conclusion TLR2 protein is involved in chronic ischemic white matter demyelination. It is suggested that the up-regulation of TLR2 protein may cause down-regulation of CNPase protein expression and decrease of oligodendrocyte on the one hand. On the other hand, it hinders the differentiation and maturation of oligodendrocyte precursor cells, thus affecting myelin regeneration and demyelinating lesions.
【學(xué)位授予單位】：西南醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R744.5

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 李海龍;畢曉瑩;;小膠質(zhì)細(xì)胞激活介導(dǎo)非特異性炎癥在血管性認(rèn)知障礙白質(zhì)脫髓鞘損傷機(jī)制中的研究進(jìn)展[J];中國卒中雜志;2015年09期

2 張利莎;李珊珊;李斌;呂文明;;缺血性腦白質(zhì)病變的研究進(jìn)展[J];中華腦科疾病與康復(fù)雜志(電子版);2015年02期

3 陳瑩瑩;孫光玲;蘭倩;潘麗麗;呂會娟;蘇志強(qiáng);;Toll樣受體與腦缺血[J];現(xiàn)代生物醫(yī)學(xué)進(jìn)展;2014年12期

4 腦小血管病診治專家共識組;;腦小血管病診治專家共識[J];中國臨床醫(yī)生;2014年01期

5 陳靈麗;任明山;;小膠質(zhì)細(xì)胞Toll樣受體2與腦缺血[J];國際腦血管病雜志;2013年10期

6 赫天一;王澤;陸宇燕;劉宏鑫;;Toll樣受體2的研究進(jìn)展[J];沈陽師范大學(xué)學(xué)報(bào)(自然科學(xué)版);2013年01期

7 高陽;;缺血性腦白質(zhì)病變[J];腦與神經(jīng)疾病雜志;2011年06期

8 李光照;杭春華;;Toll樣受體在腦損傷中的作用機(jī)制和研究進(jìn)展[J];醫(yī)學(xué)研究生學(xué)報(bào);2010年12期

9 高杰;張桂青;王偉;謝敏杰;;NG2膠質(zhì)細(xì)胞在中樞神經(jīng)系統(tǒng)中的表達(dá)與功能[J];神經(jīng)損傷與功能重建;2010年02期

10 王娟;張微微;魏微;;腦白質(zhì)損傷與慢性缺血的相關(guān)性[J];中國卒中雜志;2010年02期

，

本文編號：1444645