本文選題：腦缺血再灌注損傷　切入點(diǎn)：Bcl-2　出處：《青島大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的通過(guò)建立大鼠腦缺血再灌注損傷模型,觀察醒腦靜、丁苯酞及二者聯(lián)合應(yīng)用分別對(duì)實(shí)驗(yàn)性大鼠腦缺血再灌注損傷后神經(jīng)細(xì)胞凋亡及Bcl-2和Bax表達(dá)的影響,明確醒腦靜、丁苯酞對(duì)大鼠腦缺血再灌注損傷后的腦保護(hù)作用。并通過(guò)Bcl-2和Bax表達(dá)的變化,探討其可能的作用機(jī)制。方法(1)60只成年雄性wistar大鼠(250±20g)隨機(jī)分為4組,模型組(n=15)、醒腦靜組(n=15)、丁苯酞組(n=15)、醒腦靜聯(lián)合丁苯酞組即聯(lián)合用藥組(n=15)。每組又分為6h、24h、72h三個(gè)亞組。(2)大鼠實(shí)驗(yàn)性腦缺血再灌注模型(大腦中動(dòng)脈閉塞(Middle cerebral artery occlusion,MCAO)模型)的制備采用改良線栓法。(3)細(xì)胞凋亡的檢測(cè)采用原位末端轉(zhuǎn)移酶標(biāo)記技術(shù)(TUNEL);腦缺血再灌注損傷后腦組織形態(tài)學(xué)檢測(cè)采用HE染色,光鏡下觀察的方法;大鼠腦缺血再灌注各個(gè)時(shí)間點(diǎn)Bcl-2、Bax的表達(dá)的檢測(cè)采用免疫組化法。結(jié)果1.HE染色顯示:模型組造模側(cè)腦組織結(jié)構(gòu)變得疏松,細(xì)胞間質(zhì)水腫,部分形成空腔,著色變淺。神經(jīng)細(xì)胞個(gè)數(shù)顯著減少,細(xì)胞胞體縮小,部分細(xì)胞輪廓不清,有不同程度的神經(jīng)細(xì)胞變性、壞死。其中模型組破壞為著,醒腦靜組、丁苯酞組神經(jīng)細(xì)胞破壞較輕,聯(lián)合用藥組神經(jīng)細(xì)胞破壞最少。2.TUNEL染色顯示:TUNEL陽(yáng)性細(xì)胞數(shù)總體趨勢(shì)是模型組最高,醒腦靜組及丁苯酞組不同程度降低,醒腦靜聯(lián)合丁苯酞組最低。丁苯酞組與模型組,聯(lián)合用藥組與模型組及丁苯酞組與聯(lián)合用藥組之間在6h、24h、72h時(shí)間點(diǎn)的差異均有統(tǒng)計(jì)學(xué)意義(P0.05),而醒腦靜組與模型組的比較僅24h時(shí)間點(diǎn)上差距有統(tǒng)計(jì)學(xué)意義(P0.05)。3.免疫組化顯示:丁苯酞組及聯(lián)合用藥組在6h、24h、72h時(shí)間點(diǎn)Bcl-2陽(yáng)性表達(dá)較模型組均有提高。聯(lián)合用藥組Bcl-2陽(yáng)性表達(dá)在各時(shí)間點(diǎn)均最高,醒腦靜組在各時(shí)間點(diǎn)與模型組比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。丁苯酞組及聯(lián)合用藥組在6h、24h、72h時(shí)間點(diǎn)Bax陽(yáng)性表達(dá)較模型組均有降低(P0.05)。聯(lián)合用藥組Bax陽(yáng)性表達(dá)在各時(shí)間點(diǎn)均最低,與丁苯酞組在各時(shí)間點(diǎn)比較差異有統(tǒng)計(jì)學(xué)意義(P0.05)。醒腦靜組在各時(shí)間點(diǎn)與模型組比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。Bcl-2于6h明顯開(kāi)始升高,24h達(dá)高峰,同時(shí)Bax于6h表達(dá)較少,24h表達(dá)最低;醒腦靜聯(lián)合丁苯酞的聯(lián)合給藥組Bcl-2陽(yáng)性表達(dá)在各時(shí)問(wèn)點(diǎn)均最高。同時(shí)Bax陽(yáng)性表達(dá)在各時(shí)間點(diǎn)均最低(P0.05)。結(jié)論1.醒腦靜、丁苯酞及二者聯(lián)合均可通過(guò)抑制腦缺血再灌注損傷后神經(jīng)細(xì)胞凋亡來(lái)實(shí)現(xiàn)神經(jīng)細(xì)胞保護(hù)作用,其中二者聯(lián)合效果最佳。2.丁苯酞可通過(guò)增加腦缺血再灌注損傷大鼠Bcl-2表達(dá),減少Bax表達(dá)的方式來(lái)減少神經(jīng)細(xì)胞凋亡,從而減輕腦缺血再灌注損傷。3.醒腦靜本身不能對(duì)Bcl-2、Bax的表達(dá)產(chǎn)生影響,但其可通過(guò)增強(qiáng)丁苯酞作用的方式影響B(tài)cl-2、Bax的表達(dá),從而減輕腦缺血再灌注損傷。
[Abstract]:Objective to observe the effects of Xingnaojing, butyphthalide and their combination on neuronal apoptosis and the expression of Bcl-2 and Bax after cerebral ischemia-reperfusion injury in rats, and to observe the effects of Xingnaojing, butyphthalide and their combination on neuronal apoptosis and expression of Bcl-2 and Bax in rats with cerebral ischemia-reperfusion injury. The protective effect of butyphthalide on brain after cerebral ischemia-reperfusion injury in rats was studied. The possible mechanism of butyphthalide was investigated by the changes of Bcl-2 and Bax expressions. Methods 60 adult male wistar rats were randomly divided into 4 groups. Model group, Xingnaojing group, butyrophthalide group and butyrophthalide group respectively. Each group was divided into three subgroups (6 h, 24 h, 72 h), and the experimental cerebral ischemia reperfusion model (middle cerebral artery occlusion MCAO) was established in each group. In situ terminal transferase labeling technique was used to detect apoptosis, and cerebral histomorphology was detected by HE staining after cerebral ischemia-reperfusion injury. Immunohistochemical method was used to detect the expression of Bcl-2P Bax at different time points after cerebral ischemia-reperfusion in rats. Results 1. He staining showed that the brain structure of the model group became loose, the interstitial edema, and some cavities were formed. The number of nerve cells decreased significantly, the cell body shrank, the outline of some cells was unclear, and there were varying degrees of degeneration and necrosis of nerve cells, among which the model group was damaged, the Xingnaojing group and butyphthalide group were less damaged. The neuronal damage in combination group was the least. 2. Tunel staining showed that the total number of positive cells in the model group was the highest, Xingnaojing group and butyphthalide group were lower, Xingnaojing combined with butyphthalide group was the lowest, butyrophthalide group and model group were the lowest. The differences between the combined group and the model group and the butyphthalide group and the combined treatment group were statistically significant at the time points of 6h and 24h and 72h, but the difference between the Xingnaojing group and the model group was only significant at 24 hours. The results showed that the positive expression of Bcl-2 in butyphthalide group and combined treatment group was higher than that in model group at 6h and 24h / 72h, and the positive expression of Bcl-2 was the highest in combination group at each time point. There was no significant difference between Xingnaojing group and model group at each time point (P 0.05). The positive expression of Bax in butadiphthalide group and combined treatment group was significantly lower than that in model group at 24 h and 72 h. The positive expression of Bax in combination group was the lowest at all time points. There was no significant difference between Xingnaojing group and model group at each time point (P 0.05). The expression of Bax began to increase at 6 h and reached the peak at 24 h, while the expression of Bax was lower at 6 h than that in the model group (P 0. 05%, P 0. 05, P 0. 05, P 0. 05, P 0. 05, P 0. 05, P 0. 05, P 0. 05, P 0. 05, P 0. 05). The positive expression of Bcl-2 was the highest at each time point, and the expression of Bax was the lowest in each time point. Conclusion 1.Xingnaojing, xingnaojing, and butyphthalide combined with butyphthalide have the highest positive expression of Bcl-2 at each time point. The protective effect of butyphthalide and its combination can be achieved by inhibiting neuronal apoptosis after cerebral ischemia-reperfusion injury, and the best combination of them is .2.Butylphthalide can increase the expression of Bcl-2 in rats with cerebral ischemia-reperfusion injury. Xingnaojing itself can not affect the expression of Bcl-2P Bax, but it can affect the expression of Bcl-2O Bax by enhancing the effect of butyphthalide. So as to reduce cerebral ischemia reperfusion injury.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R743.3

【參考文獻(xiàn)】

相關(guān)期刊論文 前9條

1 李鵬飛;沈梅紅;吳錦萍;張春兵;;川芎嗪抑制大鼠腦缺血再灌注損傷的機(jī)制[J];中國(guó)老年學(xué)雜志;2017年07期

2 紀(jì)海茹;孔維;趙淑敏;桑曉一;;丁苯酞對(duì)腦缺血再灌注損傷保護(hù)作用的研究進(jìn)展[J];承德醫(yī)學(xué)院學(xué)報(bào);2014年03期

3 邵小鵬;桂樹(shù)華;胡玲玲;;丁苯酞治療老年血管性癡呆的臨床療效及對(duì)精神心理量表的影響[J];中國(guó)老年學(xué)雜志;2013年22期

4 顏玲;周慶華;;黃芪多糖對(duì)缺血性腦損傷大鼠的神經(jīng)保護(hù)作用及其機(jī)制研究[J];中國(guó)應(yīng)用生理學(xué)雜志;2012年04期

5 劉慶杰;白宏英;劉春嶺;曾志磊;李楠;;烏司他丁對(duì)腦缺血-再灌注大鼠腦組織細(xì)胞色素C、凋亡誘導(dǎo)因子表達(dá)及凋亡細(xì)胞數(shù)的影響[J];臨床神經(jīng)病學(xué)雜志;2012年01期

6 楊杰;周芝文;鄭麗君;曾進(jìn);楊期東;;TrkA和Bcl-2在局灶性腦缺血再灌注大鼠大腦皮質(zhì)中的表達(dá)[J];中風(fēng)與神經(jīng)疾病雜志;2010年07期

7 胡偉東;胡耀祖;黃小平;;中藥有效成分對(duì)腦缺血再灌注損傷保護(hù)作用的研究進(jìn)展[J];實(shí)用心腦肺血管病雜志;2010年01期

8 孫宇;嚴(yán)國(guó)鋒;姜虹;朱也森;;改良線栓法大鼠大腦中動(dòng)脈阻塞模型的建立[J];中國(guó)比較醫(yī)學(xué)雜志;2008年08期

9 王興盛;苗莉;姚小梅;朱學(xué)良;;大鼠腦缺血再灌注后血腦屏障超微結(jié)構(gòu)的改變[J];天津醫(yī)藥;2006年03期

，

本文編號(hào)：1608924