發(fā)布時(shí)間：2018-02-13 08:10

  本文關(guān)鍵詞： 腦梗塞 脾切除術(shù) 免疫 炎癥 大鼠　出處：《中山大學(xué)》2012年碩士論文　論文類(lèi)型：學(xué)位論文

【摘要】：背景和目的 卒中是最常見(jiàn)的神經(jīng)科疾患，是由各種血管性病因引起的腦部疾病的總稱(chēng)。其中絕大部分（80％以上）為缺血性腦卒中，由于各種原因未能早期診斷和有效治療，其中有10％的病人死亡，50％以上的病人留有永久性殘疾，給患者本人、家庭和社會(huì)均造成沉重的負(fù)擔(dān)。 急性腦梗塞的治療目前仍富有挑戰(zhàn)，需要繼續(xù)尋找新的治療手段。尋找新的治療方法，需要對(duì)腦梗塞的病理生理機(jī)制進(jìn)行更深入的研究。然而，腦梗塞的病理生理機(jī)制非常復(fù)雜，主要包括以下幾方面：酸中毒，細(xì)胞內(nèi)鈣離子超載，興奮性氨基酸（excitatory amino acids，EAAs）毒性，，炎癥細(xì)胞因子的損害。目前免疫調(diào)節(jié)治療在動(dòng)物實(shí)驗(yàn)中取得了一定的成果。免疫調(diào)節(jié)治療可能是腦梗塞治療的一個(gè)突破口。 脾臟作為主要的免疫器官，在腦梗塞后的腦損傷機(jī)制中發(fā)揮重要作用。研究發(fā)現(xiàn)，腦梗塞之后，脾臟會(huì)出現(xiàn)明顯萎縮，脾臟的功能會(huì)發(fā)生改變。有學(xué)者認(rèn)為，脾臟可能是腦梗塞治療的一個(gè)潛在靶點(diǎn)。目前國(guó)際上關(guān)于脾臟與腦梗塞的關(guān)系的研究并不多見(jiàn)，國(guó)內(nèi)未見(jiàn)相關(guān)研究。因此有必要對(duì)脾與腦梗塞的關(guān)系進(jìn)行更深一步的研究。 本研究對(duì)脾切除大鼠采用線(xiàn)栓法建立大腦中動(dòng)脈閉塞（middle cerebral arteryocclusion，MCAO）模型，探討脾切除對(duì)大鼠腦梗塞的影響及其可能機(jī)制。 方法 （1）動(dòng)物分組：將健康雄性Sprague-Dawley（SD）大鼠隨機(jī)分為三組：MCAO對(duì)照組、假脾切除組、脾切除組，每組12只。 （2）脾切除模型的制作：按大鼠腹部手術(shù)常規(guī)開(kāi)腹，分離結(jié)扎血管，切除脾臟，徹底止血后關(guān)腹。假脾切除組找到脾臟后游離脾臟，余同脾切除組。 （3）MCAO模型的制作：采用線(xiàn)栓法建立MCAO大鼠模型。 （4）尼氏小體染色測(cè)定腦梗塞的體積。 （5）免疫熒光法檢測(cè)腦缺血區(qū)T細(xì)胞、中性粒細(xì)胞、巨噬細(xì)胞。 （6）ELISA方法測(cè)定缺血側(cè)腦勻漿和血清的IL-1β、TNF-α、IL-10水平。 結(jié)果 （1）脾切除組大鼠腦梗塞體積為34.93%±3.23%，比假脾切除組減少53.01%（74.33%±2.36%，P 0.001），比MCAO對(duì)照組減少54.81%（77.30%±2.62%，P 0.001）。 （2）在腦缺血區(qū)，MCAO對(duì)照組（52.15±10.85/mm~2，p 0.001）和假脾切除組（46.46±13.44/mm~2，p 0.001）的T細(xì)胞數(shù)量較脾切除組（17.44±7.33/mm~2）明顯增多。 （3）在腦缺血區(qū)，MCAO對(duì)照組（56.46±11.25/mm~2，p=0.001）和假脾切除組（47.56±9.04/mm~2，p=0.032）的中性粒細(xì)胞較脾切除組（35.56±4.83/mm~2）明顯增多。 （4）在腦缺血區(qū)，MCAO對(duì)照組（39.31±8.69/mm~2，p 0.001）和假脾切除組（43.13±9.10/mm~2，p 0.001）的巨噬細(xì)胞數(shù)量較脾切除組（7.08±2.23/mm~2）明顯增多。 （5）缺血側(cè)腦勻漿炎癥因子：MCAO對(duì)照組（23.06±7.01pg/mg，p=0.04）和假脾切除組（24.04±4.81pg/mg，p=0.02）的腦勻漿IL-1β濃度較脾切除組（16.63±1.09pg/mg）明顯增高。MCAO對(duì)照組（2.20±0.29pg/mg，p=0.01）和假脾切除組（2.09±0.39pg/mg，p=0.034）的腦勻漿TNF-α濃度較脾切除組（1.71±0.10pg/mg）明顯增高。對(duì)于IL-10來(lái)說(shuō)，趨勢(shì)剛好相反，脾切除組腦勻漿IL-10的濃度（1.14±0.28pg/mg）較MCAO對(duì)照組（0.67±0.22pg/mg，p=0.002）和假脾切除增高（0.58±0.09pg/mg，p 0.001）。 （6）血清炎癥因子：IL-1β, TNF-α的ELISA結(jié)果與腦勻漿的結(jié)果相符，具有相同的趨勢(shì)。IL-10各個(gè)組之間的差異沒(méi)有統(tǒng)計(jì)學(xué)意義。 結(jié)論 （1）脾臟切除能明顯減少M(fèi)CAO大鼠模型的腦梗塞體積。 （2）脾臟切除改善腦梗塞可能與炎癥細(xì)胞（T細(xì)胞、中性粒細(xì)胞、巨噬細(xì)胞）的減少有關(guān)。 （3）脾臟切除改善腦梗塞可能與促炎因子（IL-1β和TNF-α）的減少有關(guān)。 （4）脾臟切除改善腦梗塞可能與抗炎因子（IL-10）的增多有關(guān)。
[Abstract]:Background and Purpose Stroke is the most common neurological disease , which is the general name of brain disease caused by various vascular aetiologies . Most of the patients ( more than 80 % ) are ischemic stroke , with 10 % of the patients died and more than 50 % of the patients left permanent disability , resulting in a heavy burden on the patients themselves , the family and society . However , the pathological and physiological mechanism of cerebral infarction is very complex , including the following aspects : acidosis , overload of intracellular calcium ion , excitatory amino acids ( EAAs ) toxicity , and damage of inflammatory cytokines . Immunoregulatory treatment may be a breakthrough in the treatment of cerebral infarction . The spleen , as the main immune organ , plays an important role in the mechanism of brain damage after cerebral infarction . It has been found that spleen may be a potential target for the treatment of cerebral infarction after cerebral infarction . Some scholars believe that the spleen may be a potential target for cerebral infarction treatment . At present , the study of the relationship between spleen and cerebral infarction is not uncommon . There is no correlation study in China . Therefore , it is necessary to study the relationship between spleen and cerebral infarction . In order to study the effect of splenic resection on cerebral infarction in rats and its possible mechanism , the rat model of middle cerebral artery occlusion was established . method ( 1 ) Group of animals : healthy male Sprague - Dawley ( SD ) rats were randomly divided into three groups : the control group , sham - splenic resection group and the splenic resection group , 12 rats in each group . ( 2 ) The spleen resection model was made : the abdominal operation of the rats was performed routinely , the ligation vessel was separated , the spleen was removed , the spleen was removed , and the spleen was removed completely . The spleen was removed from the spleen after the spleen was removed , and the remainder was removed from the spleen . ( 3 ) Making rat model by line plug method . ( 4 ) The volume of cerebral infarction was determined by Nissella staining . ( 5 ) Immunofluorescence assay was used to detect T cells , neutrophils and macrophages in cerebral ischemia area . ( 6 ) The levels of IL - 1尾 , TNF - 偽 and IL - 10 were determined by ELISA . Results ( 1 ) The volume of cerebral infarction in the spleen resection group was 34.93 % 鹵 3.23 % , which was 53.01 % ( 74.33 % 鹵 2.36 % , P 0.001 ) than the sham - splenic resection group , which was 54.81 % ( 77.30 % 鹵 2.62 % , P 0.001 ) than the control group . ( 2 ) In the cerebral ischemic area , the number of T cells ( 52.15 鹵 10.85 / mm ~ 2 , p 0.001 ) and sham - splenic resection group ( 46.46 鹵 13.44 / mm ~ 2 , p 0.001 ) were significantly higher than those in the spleen resection group ( 17.44 鹵 7.33 / mm ~ 2 ) . ( 3 ) In the focal cerebral ischemic area , the neutropenia group ( 56.46 鹵 11.25 / mm ~ 2 , p = 0.001 ) and sham - splenic resection group ( 47.56 鹵 9.04 / mm ~ 2 , p = 0.032 ) were significantly higher than those in the spleen resection group ( 35.56 鹵 4.83 / mm ~ 2 ) . ( 4 ) In the cerebral ischemic area , the number of macrophages ( 39.31 鹵 8.69 / mm ~ 2 , p 0.001 ) and sham - splenic resection group ( 43.13 鹵 9.10 / mm ~ 2 , p 0.001 ) were significantly higher than those in the splenic resection group ( 7.08 鹵 2.23 / mm ~ 2 ) . ( 5 ) The level of IL - 1尾 in the brain homogenate was significantly higher than that in the spleen resection group ( 16.63 鹵 1.09pg / mg , p = 0.04 ) and sham - splenic resection group ( 24.04 鹵 4.81pg / mg , p = 0.034 ) . The concentration of IL - 10 ( 1.14 鹵 0.28pg / mg , p = 0.002 ) and sham - spleen resection group increased significantly ( 0 . 58 鹵 0 . 09pg / mg , p 0.001 ) . ( 6 ) Serum inflammatory factors : IL - 1尾 , TNF - 偽 ELISA results were consistent with the results of brain homogenates , with the same trend . There was no statistical significance between IL - 10 and IL - 10 . mg,p= ( 1 ) Splenectomy can significantly reduce the volume of cerebral infarction in the rat model . ( 2 ) Splenectomy improving cerebral infarction may be associated with a decrease in inflammatory cells ( T cells , neutrophils , macrophages ) . ( 3 ) The improvement of cerebral infarction with spleen resection may be related to the reduction of pro - inflammatory factors ( IL - 1尾 and TNF - 偽 ) . ( 4 ) The improvement of cerebral infarction with spleen resection may be related to the increase of anti - inflammatory factor ( IL - 10 ) .

【學(xué)位授予單位】：中山大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類(lèi)號(hào)】：R-332

【共引文獻(xiàn)】

相關(guān)期刊論文 前4條

1 郭芮兵;朱武生;劉新峰;;疾病狀態(tài)下血腦屏障對(duì)大分子物質(zhì)的轉(zhuǎn)運(yùn)途徑[J];中風(fēng)與神經(jīng)疾病雜志;2006年01期

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相關(guān)會(huì)議論文 前1條

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2 夏春義;低頻超聲輻照聯(lián)合小劑量緩激肽增加血腫瘤屏障通透性機(jī)制的研究[D];中國(guó)醫(yī)科大學(xué);2008年

相關(guān)碩士學(xué)位論文 前4條

1 陶裕川;低頻低功率超聲誘導(dǎo)C_6膠質(zhì)瘤細(xì)胞凋亡的初步研究[D];重慶醫(yī)科大學(xué);2007年

2 楊延慶;MRI引導(dǎo)聚焦超聲聯(lián)合微泡靶向開(kāi)放血腦屏障[D];重慶醫(yī)科大學(xué);2008年

3 張雪華;超聲聯(lián)合載卡莫司汀脂質(zhì)微泡治療大鼠腦膠質(zhì)瘤的研究[D];重慶醫(yī)科大學(xué);2009年

4 汪峰;MRI監(jiān)測(cè)聚焦超聲聯(lián)合微泡介導(dǎo)兔血腦屏障開(kāi)放及通透性變化規(guī)律[D];重慶醫(yī)科大學(xué);2010年

本文編號(hào)：1507703