本文選題：腦出血 + CORM-2�。� 參考：《南昌大學(xué)》2017年碩士論文

【摘要】：目的與背景:腦出血是一種常見(jiàn)的、致命的卒中亞型,出血后灶周組織小膠質(zhì)細(xì)胞被激活,釋放大量炎癥因子和趨化因子,啟動(dòng)繼發(fā)性腦損傷。因此調(diào)控灶周炎癥反應(yīng)對(duì)減輕腦出血繼發(fā)性損傷具有重要意義。內(nèi)源性CO產(chǎn)生的主要途徑是HO-1催化血紅素降解過(guò)程,目前已有眾多學(xué)者應(yīng)用CORM-2來(lái)研究CO的生物學(xué)效應(yīng),在體和離體研究均發(fā)現(xiàn)低濃度的CO具有抗炎性損傷的作用。本研究采用CORM-2干預(yù),提高體內(nèi)CO含量,通過(guò)建立腦出血?jiǎng)游锬Ｐ?進(jìn)行在體實(shí)驗(yàn)研究,觀察CORM-2對(duì)腦出血后灶周炎性損傷的影響并探討其相關(guān)機(jī)制。方法:采用自體股動(dòng)脈血注入大鼠基底節(jié)區(qū)建立腦出血模型,隨機(jī)將SD大鼠分為以下4個(gè)實(shí)驗(yàn)組:正常對(duì)照組、單純ICH組、CORM-2+ICH組和iCORM-2+ICH組,每組各5只,分別在ICH術(shù)后6h、24h、48h和5d采用Gareia18分測(cè)評(píng)法對(duì)大鼠進(jìn)行神經(jīng)功能評(píng)分,評(píng)分后收集大鼠腦組織標(biāo)本,采用Western Blot檢測(cè)腦組織中HO-1、IKKβ、NF-κB p65以及TNF-α蛋白表達(dá)情況,免疫熒光雙標(biāo)染色方法檢測(cè)灶周小膠質(zhì)細(xì)胞活化情況以及炎癥因子TNF-α與小膠質(zhì)細(xì)胞共表達(dá)情況。結(jié)果:(1)大鼠腦出血術(shù)后神經(jīng)功能評(píng)分在術(shù)后各時(shí)間點(diǎn)均有所下降,且在48h評(píng)分最低(P0.05);CORM-2干預(yù)可改善大鼠神經(jīng)缺損癥狀。(2)與正常對(duì)照組相比,ICH組術(shù)后6h灶周IKKβ及炎性因子NF-κB p65和TNF-α蛋白表達(dá)均開(kāi)始升高(P0.05),48h達(dá)高峰(P0.05),且持續(xù)到第5天表達(dá)量仍高于正常對(duì)照組(P0.05);抗氧化蛋白HO-1表達(dá)趨勢(shì)與TNF-α蛋白基本一致(P0.05)。(3)CORM-2干預(yù)組與ICH組比較,IKKβ、NF-κB p65及TNF-α蛋白表達(dá)水平均有不同程度的減少,且在48h下降最明顯(P0.05);同時(shí)HO-1表達(dá)明顯增加(P0.05)。(4)大鼠腦出血后小膠質(zhì)細(xì)胞活化,表現(xiàn)為術(shù)后6h灶周大量Iba-1標(biāo)記的陽(yáng)性細(xì)胞,且熒光雙標(biāo)染色發(fā)現(xiàn)大多數(shù)為T(mén)NF-α與Iba-1標(biāo)記共表達(dá)陽(yáng)性細(xì)胞,CORM-2干預(yù)組術(shù)后5天TNF-α與Iba-1標(biāo)記共表達(dá)陽(yáng)性細(xì)胞比例較ICH組明顯減少(P0.05)。(5)iCORM-2干預(yù)組較ICH組各蛋白表達(dá)及神經(jīng)功能評(píng)分無(wú)明顯差異(P0.05)。結(jié)論:(1)大鼠腦出血后6h灶周IKK/NF-κB通路開(kāi)始被激活;(2)CORM-2干預(yù)可有效地增加HO-1表達(dá),抑制IKKβ及炎性因子NF-κB p65和TNF-α的表達(dá);(3)大鼠腦出血后CORM-2可能通過(guò)抑制IKK/NF-κB信號(hào)通路,抑制炎癥因子TNF-α的表達(dá),從而減輕腦損傷,改善大鼠神經(jīng)功能損傷。(4)CORM-2的抗炎作用可能與灶周小膠質(zhì)細(xì)胞有關(guān)。
[Abstract]:Objective and background: intracerebral hemorrhage (ICH) is a common and fatal subtype of stroke. After intracerebral hemorrhage microglia are activated release a large number of inflammatory factors and chemokines and initiate secondary brain injury. Therefore, the regulation of perifocal inflammation is of great significance in alleviating secondary injury of intracerebral hemorrhage. The main pathway of endogenous CO production is HO-1 catalyzing heme degradation. At present, many researchers have applied CorM-2 to study the biological effect of CO. In vitro and in vitro, it has been found that low concentration of CO has anti-inflammatory effect. In this study, CorM-2 intervention was used to increase CO content in vivo. By establishing animal model of intracerebral hemorrhage, in vivo experimental study was carried out to observe the effect of CorM-2 on perifocal inflammatory injury after intracerebral hemorrhage and to explore its related mechanism. Methods: intracerebral hemorrhage model was established by injecting autologous femoral arterial blood into the basal ganglia of rats. SD rats were randomly divided into four groups: normal control group, ICH group (ICH group), CorM-2 ICH group and iCorM-2 ICH group (5 rats in each group). The neurological function of rats was evaluated with Gareia 18 score at 6 h, 24 h, 48 h and 5 d after ICH. The brain tissue samples were collected. Western blot was used to detect the expression of HO-1IKK 尾 -NF- 魏 B p65 and TNF- 偽 protein in brain tissue. The activation of microglia and the co-expression of inflammatory factor TNF- 偽 with microglia were detected by double immunofluorescence staining. Results the neurological function score of rats with intracerebral hemorrhage decreased at all time points after ICH. And the lowest P0.05CorM-2 intervention at 48h could improve the symptom of nerve defect in rats.) compared with the normal control group, the expression of IKK 尾 and inflammatory factors NF- 魏 B p65 and TNF- 偽 began to increase in ICH group at 6h after operation, and reached the peak at 48h, and lasted until the 5th day. The expression trend of HO-1 and TNF- 偽 protein was similar to that of TNF- 偽 protein, and the expression levels of Ike 尾 -NF- 魏 B p65 and TNF- 偽 protein in ICH group and ICH group were decreased in different degrees. The expression trend of HO-1 protein was similar to that of TNF- 偽 protein in ICH group and ICH group, and the expression trend of HO-1 protein was similar to that of TNF- 偽 protein in ICH group and ICH group. The expression of HO-1 significantly increased the activation of microglia after intracerebral hemorrhage in rats, which was characterized by a large number of Iba-1 labeled positive cells around the focal area 6 h after operation. Fluorescence double labeling staining showed that the proportion of TNF- 偽 and Iba-1 co-expressed cells in CorM-2 intervention group was significantly lower than that in ICH group on the 5th day after operation compared with ICH group. The expression of each protein and neuronal work in ICH group was significantly lower than that in ICH group, and the ratio of TNF- 偽 and Iba-1 co-expressed positive cells in ICH group was significantly lower than that in ICH group. There was no significant difference in energy score (P 0.05). Conclusion the activation of IKK / NF- 魏 B pathway at 6 h after intracerebral hemorrhage can effectively increase the expression of HO-1, and inhibit the expression of IKK 尾 and inflammatory factors NF- 魏 B p65 and TNF- 偽. CorM-2 may inhibit IKK- / NF- 魏 B signal pathway after intracerebral hemorrhage in rats. Inhibiting the expression of inflammatory factor TNF- 偽, thus reducing brain injury, and improving the anti-inflammatory effect of Corm-2 in rats with nerve function injury may be related to the microglia around the focal area.
【學(xué)位授予單位】：南昌大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R743.34

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 Chen SH;Oyarzabal EA;Sung YF;Chu CH;Wang Q;Chen SL;Lu RB;Hong JS;唐穎馨;;小膠質(zhì)細(xì)胞對(duì)星形膠質(zhì)細(xì)胞的免疫和神經(jīng)保護(hù)功能的調(diào)節(jié)作用(英文)[J];神經(jīng)損傷與功能重建;2015年01期

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本文編號(hào)：1996777