王 玨， 趙海蘋

(1首都醫(yī)科大學(xué)宣武醫(yī)院腦血管病研究室， 北京100053； 2中國醫(yī)科大學(xué)附屬盛京醫(yī)院神經(jīng)內(nèi)科， 遼寧 沈陽 110004)

MicroRNA調(diào)控缺血性及出血性腦血管病過程中免疫反應(yīng)的研究進(jìn)展*

王 玨1, 2， 趙海蘋1△

(1首都醫(yī)科大學(xué)宣武醫(yī)院腦血管病研究室， 北京100053；2中國醫(yī)科大學(xué)附屬盛京醫(yī)院神經(jīng)內(nèi)科， 遼寧 沈陽 110004)

腦血管病為一類腦血液循環(huán)障礙性疾病，近年來其發(fā)病率及致死率有逐年增高的趨勢，已成為威脅中老年人生命健康及生活質(zhì)量的主要疾病。免疫反應(yīng)為引起腦血管病患者神經(jīng)功能損傷的主要原因之一，在缺血或出血后的數(shù)分鐘至數(shù)小時(shí)內(nèi)，激活的小膠質(zhì)細(xì)胞及細(xì)胞死亡產(chǎn)物可誘導(dǎo)級聯(lián)免疫反應(yīng)[1]，造成血管及腦實(shí)質(zhì)的損傷[2]。免疫反應(yīng)的激活離不開炎癥介質(zhì)及細(xì)胞因子，其產(chǎn)生受轉(zhuǎn)錄或者轉(zhuǎn)錄后調(diào)控，轉(zhuǎn)錄調(diào)控主要依賴于轉(zhuǎn)錄因子，如API、NF-κB[3]，而轉(zhuǎn)錄后水平的調(diào)控則由非編碼RNA完成。非編碼RNA為一類不可編碼任何蛋白質(zhì)的RNA，近期研究發(fā)現(xiàn)非編碼RNA主要通過調(diào)節(jié)蛋白的翻譯過程影響蛋白合成。由于缺血或出血可引起組織缺氧導(dǎo)致細(xì)胞轉(zhuǎn)錄活性抑制，促使機(jī)體無法通過轉(zhuǎn)錄調(diào)控作用誘導(dǎo)炎癥介質(zhì)或細(xì)胞因子的合成，非編碼RNA調(diào)控蛋白表達(dá)不依賴于機(jī)體的轉(zhuǎn)錄活性，因此在腦血管病誘導(dǎo)的免疫反應(yīng)中必然有非編碼RNA的參與。目前，在腦血管病領(lǐng)域，研究最為深入的非編碼RNA為微小RNA(microRNAs，miRNA，miR)。miRNA是一類長度小于22個(gè)核苷酸的非編碼RNA，可在多種病理生理過程中發(fā)揮作用[4]。一種miRNA可以調(diào)節(jié)多種基因的表達(dá)，約90%人類基因都受到miRNA的調(diào)控。miRNA通過與其靶基因的3’非翻譯區(qū)的互補(bǔ)序列結(jié)合誘導(dǎo)靶基因mRNA降解或者通過抑制靶基因翻譯減少其表達(dá)。miRNA具有表達(dá)穩(wěn)定，作用廣泛迅速且易于干預(yù)的特點(diǎn)，在腦血管病領(lǐng)域中受到研究者的重視[5]。近期研究開始關(guān)注miRNA對于免疫系統(tǒng)的調(diào)節(jié)。miRNA可通過調(diào)節(jié)免疫相關(guān)信號(hào)通路[6]、受體[7]及免疫調(diào)節(jié)細(xì)胞[8]調(diào)控免疫反應(yīng)。本文將對miRNA在腦血管病免疫反應(yīng)中發(fā)揮的作用及其作用機(jī)制做一綜述，為腦血管病的治療提供新思路。

1 miRNA參與調(diào)節(jié)腦缺血(血管阻塞)過程中的免疫反應(yīng)

血栓栓塞是腦缺血發(fā)生的最主要的原因之一，免疫反應(yīng)的激活可以誘導(dǎo)血管壁及其周圍組織炎癥，改變血管反應(yīng)性，促進(jìn)動(dòng)脈粥樣硬化斑塊的產(chǎn)生導(dǎo)致血栓形成，導(dǎo)致缺血性腦卒中的發(fā)生[9-10]。缺血性腦卒中發(fā)生后，血供中斷導(dǎo)致的急性血管反應(yīng)，腦組織損傷以及修復(fù)過程中都有免疫系統(tǒng)的參與，免疫系統(tǒng)活化不僅可以通過激活固有免疫系統(tǒng)誘導(dǎo)炎癥反應(yīng)加劇組織損傷，其也可通過識(shí)別潛伏于血腦屏障的抗原激活獲得性免疫反應(yīng)發(fā)揮破壞性作用[1]。此外，腦缺血還可通過自主神經(jīng)系統(tǒng)抑制免疫器官導(dǎo)致感染的發(fā)生，增加腦卒中患者的致殘率和致死率[11]。因此，免疫反應(yīng)與缺血腦組織的最終結(jié)局以及腦卒中患者的生存率密切相關(guān)。研究證實(shí)miRNA可參與調(diào)節(jié)腦缺血再灌注損傷過程中的免疫反應(yīng)。在局灶腦缺血及前腦缺血的大鼠腦組織[12]以及缺血性腦卒中患者血漿中[13]應(yīng)用miRNA高通量篩查的手段發(fā)現(xiàn)腦缺血可導(dǎo)致多種miRNA水平的改變。應(yīng)用生物信息軟件分析發(fā)現(xiàn)，這些差異表達(dá)的miRNA有許多共同的靶向mRNA，其中包括與免疫相關(guān)的IL-1β、IL-6、巨噬細(xì)胞炎癥蛋白1α(macrophage inflammatory protein 1α，MIP1α)、單核細(xì)胞趨化蛋白1(monocyte chemotactic protein 1，MCP1)、細(xì)胞間黏附分子1(intercellular adhesion molecule 1，ICAM1)等[10]。

1.1 miRNA let-7 Let-7為一種高度表達(dá)于中樞神經(jīng)系統(tǒng)的miRNA，let-7的生物合成包括如下幾個(gè)步驟，首先合成初級轉(zhuǎn)錄產(chǎn)物原始let-7(pri-let-7)，在細(xì)胞核內(nèi)pri-let-7被Drosha復(fù)合物分解產(chǎn)生前體let-7(prelet-7)，其被轉(zhuǎn)運(yùn)入細(xì)胞質(zhì)并在細(xì)胞質(zhì)內(nèi)由Dicer復(fù)合物加工形成成熟的let-7[14]。RNA結(jié)合蛋白LIN28和hnRNP A1可抑制let-7的加工[15-16]，而KH型剪切調(diào)節(jié)蛋白(KH type splicing regulatory protein，KSRP)可促進(jìn)let-7的合成[17]。損傷的神經(jīng)元及免疫細(xì)胞可釋放let-7，let-7可通過抑制其靶向mRNA的翻譯或者增加其降解[18]，加劇神經(jīng)系統(tǒng)損傷。在新生兒缺血缺氧性腦病動(dòng)物模型中發(fā)現(xiàn)，KSRP可通過Toll 樣受體4(Toll-like receptor 4，TLR4)依賴性途徑誘導(dǎo)let-7的合成，let-7合成后可通過轉(zhuǎn)錄后調(diào)控機(jī)制減少IL-10的產(chǎn)生[19]。IL-10為一種抗炎因子，可抑制NF-κB激活[20]，阻止其誘導(dǎo)促炎因子轉(zhuǎn)錄[21]。在腦缺血前或缺血后短時(shí)間內(nèi)側(cè)腦室注射IL-10可減小腦梗死體積，減輕炎癥反應(yīng)及凋亡[22]。此外，IL-10還可調(diào)節(jié)let-7的表達(dá)，應(yīng)用原代培養(yǎng)的皮層神經(jīng)元氧糖剝奪模型進(jìn)行研究發(fā)現(xiàn)，IL-10可通過與神經(jīng)元上的IL-10受體結(jié)合，誘導(dǎo)Akt的磷酸化，下調(diào)let-7的表達(dá)[23]。綜上所述，let-7的下調(diào)和IL-10的分泌兩者之間存在相互調(diào)節(jié)，并以正反饋方式發(fā)揮對于神經(jīng)元的保護(hù)作用。

1.2 miR-181 miR-181家族除參與系統(tǒng)性免疫反應(yīng)，也參與調(diào)節(jié)腦缺血損傷過程中的免疫反應(yīng)。大鼠短暫腦缺血前或缺血后通過側(cè)腦室或者靜脈給予miR-181a阻斷劑不僅可以在損傷急性期(48 h內(nèi))發(fā)揮減小梗死體積，改善神經(jīng)功能的作用，還可發(fā)揮長時(shí)程(4周)神經(jīng)保護(hù)。miR-181a阻斷劑可減輕腦缺血再灌注損傷導(dǎo)致的小膠質(zhì)細(xì)胞和單核細(xì)胞激活以及中性粒細(xì)胞浸潤，減少腦缺血再灌注損傷誘導(dǎo)的NF-κB激活，減輕炎癥反應(yīng)[24]。此外，短暫局灶腦缺血再灌注損傷過程中，miR-181a還可通過其靶向蛋白——熱休克蛋白70家族的葡萄糖調(diào)節(jié)蛋白78(glucose-regulated protein 78，GRP78)以及Bcl-2抗凋亡蛋白家族的Bcl-2和髓樣細(xì)胞白血病1(myeloid cell leukemia-1，MCL1)影響線粒體的功能[20]。線粒體結(jié)構(gòu)和功能的完整性與炎癥反應(yīng)密切相關(guān)，線粒體被破壞可造成鈣離子的大量積累導(dǎo)致線粒體產(chǎn)生過量的活性氧，誘導(dǎo)NF-κB的激活及并產(chǎn)生大量的促炎因子，導(dǎo)致炎癥反應(yīng)[25-26]，損傷的線粒體還可產(chǎn)生大量的損傷相關(guān)分子模式(damage-associated molecular patterns，DAMP)分子，激活NLRP3(NACHT, LRR and PYD domains-containing protein 3)，誘導(dǎo)NLRP3炎癥小體的形成，使細(xì)胞產(chǎn)生大量的IL-1β、IL-18等促炎因子[27]。除了促炎作用，近期的研究發(fā)現(xiàn)在中樞神經(jīng)系統(tǒng)中miR-181家族還具有抗炎作用，miR-181a可通過下調(diào)單核細(xì)胞及巨噬細(xì)胞中的IL-1α發(fā)揮抗炎作用[28]，miR-181c通過靶向TNF-α mRNA的3’非翻譯區(qū)抑制TNF-α表達(dá)，miR-181c的下調(diào)可增加TNF-α的表達(dá)，增加小膠質(zhì)細(xì)胞及星形膠質(zhì)細(xì)胞氧糖剝奪時(shí)的炎癥反應(yīng)[29]。

1.3 缺血性腦卒中過程中參與調(diào)節(jié)小膠質(zhì)細(xì)胞激活的miRNA 缺血或損傷等應(yīng)激狀態(tài)可通過調(diào)節(jié)某些miRNA誘導(dǎo)小膠質(zhì)細(xì)胞的激活并增加小膠質(zhì)細(xì)胞炎癥因子分泌，促進(jìn)炎癥反應(yīng)[30]。小膠質(zhì)細(xì)胞為中樞神經(jīng)系統(tǒng)中的免疫細(xì)胞，在缺血及創(chuàng)傷性損傷中誘導(dǎo)神經(jīng)免疫反應(yīng)。在正常的中樞神經(jīng)系統(tǒng)中，小膠質(zhì)細(xì)胞不表達(dá)或只表達(dá)少量的炎癥相關(guān)蛋白[31]；缺血時(shí)，小膠質(zhì)細(xì)胞被激活，激活的小膠質(zhì)細(xì)胞可表達(dá)CD45、MHC II類復(fù)合物、CD86等表面活性標(biāo)志，并可通過產(chǎn)生TNF-α等促炎因子破壞線粒體穩(wěn)態(tài)，使神經(jīng)細(xì)胞中毒[32]。小膠質(zhì)細(xì)胞的激活過程受到miRNA的調(diào)控，miR-424可抑制細(xì)胞周期相關(guān)蛋白CDC25A、CCND1及CDK6，導(dǎo)致小膠質(zhì)細(xì)胞G1期阻滯，抑制小膠質(zhì)細(xì)胞激活，發(fā)揮對于腦缺血再灌注損傷的保護(hù)作用[33]。小膠質(zhì)細(xì)胞被激活后可釋放炎癥因子誘導(dǎo)炎癥反應(yīng)，miR-155可減少小膠質(zhì)細(xì)胞中轉(zhuǎn)錄因子c-Maf的表達(dá)，導(dǎo)致炎癥反應(yīng)[34]。

1.4 缺血性腦卒中過程中參與調(diào)節(jié)星形膠質(zhì)細(xì)胞免疫反應(yīng)的miRNA 缺血或缺氧時(shí)，免疫反應(yīng)可通過誘導(dǎo)星形膠質(zhì)細(xì)胞釋放谷氨酸導(dǎo)致神經(jīng)元損傷，在共培養(yǎng)的神經(jīng)元和星形膠質(zhì)細(xì)胞中加入IL-1β，其可與星形膠質(zhì)細(xì)胞的IL-1R1結(jié)合導(dǎo)致谷氨酸釋放誘導(dǎo)神經(jīng)元死亡[35]。除了調(diào)控谷氨酸釋放，炎癥因子如TNF-α還可以通過減少星形膠質(zhì)細(xì)胞中谷氨酸轉(zhuǎn)運(yùn)體的表達(dá)減少谷氨酸轉(zhuǎn)運(yùn)，加劇神經(jīng)元損傷[36]。星形膠質(zhì)細(xì)胞免疫反應(yīng)過程中有miRNA的參與。人腦星形膠質(zhì)細(xì)胞中miR-146a高度表達(dá)[37]，其在星形膠質(zhì)細(xì)胞介導(dǎo)的免疫反應(yīng)中發(fā)揮重要作用。miR-146a可通過抑制腫瘤壞死因子受體相關(guān)因子6(tumor necrosis factor receptor-associated factor 6，TRAF6)和IL-1受體相關(guān)激酶1(IL-1 receptor-asso-ciated kinase 1，IRAK1)，抑制NF-κB通路，從而抑制炎癥[4]。此外，miR-146a還可通過多種星形膠質(zhì)細(xì)胞特異性miRNA促進(jìn)神經(jīng)干細(xì)胞向星形膠質(zhì)細(xì)胞分化[38]。

1.5 缺血性腦卒中過程中參與調(diào)節(jié)內(nèi)皮細(xì)胞免疫反應(yīng)的miRNA 缺血性腦卒中除了可以導(dǎo)致神經(jīng)元及膠質(zhì)細(xì)胞的損傷還可損傷血管內(nèi)皮細(xì)胞。腦血管內(nèi)皮細(xì)胞為腦微循環(huán)的主要組成成分，參與構(gòu)成血腦屏障，并可維持血腦屏障的完整性。缺血可造成內(nèi)皮細(xì)胞損傷及炎癥，導(dǎo)致內(nèi)皮細(xì)胞功能受損，血管通透性增加，血腦屏障破壞，造成并加劇神經(jīng)損傷[39]。內(nèi)皮細(xì)胞損傷過程中也有miRNA的參與，miR-125a-5p參與調(diào)節(jié)內(nèi)皮細(xì)胞之間的緊密連接，其上調(diào)可明顯增強(qiáng)腦血管內(nèi)皮細(xì)胞的屏障作用。將miR-125a-5p類似物應(yīng)用于臨床可幫助抑制炎癥反應(yīng)并修復(fù)血腦屏障功能。此外，miR-155可通過下調(diào)血管內(nèi)皮細(xì)胞之間的膜連蛋白2及緊密連接蛋白1增加血腦屏障通透性，miR-155的抑制可阻止急性炎癥導(dǎo)致的血腦屏障破壞[40]。

2 miRNA參與調(diào)節(jié)腦出血(血管破裂)誘導(dǎo)的免疫反應(yīng)

腦出血是最為兇險(xiǎn)的腦血管病之一，其致死率遠(yuǎn)遠(yuǎn)高于缺血性腦血管病，然而迄今為止尚未發(fā)現(xiàn)改善腦出血患者神經(jīng)功能的有效治療措施。臨床上較為常見的兩大類出血性腦血管病為顱內(nèi)出血和顱內(nèi)動(dòng)脈瘤破裂導(dǎo)致的蛛網(wǎng)膜下腔出血。顱內(nèi)出血可形成血腫，血腫本身可造成嚴(yán)重的腦組織損傷，血腫形成后還可激活小膠質(zhì)細(xì)胞炎癥反應(yīng)，導(dǎo)致促炎因子及趨化因子的釋放造成血腦屏障破壞引起腦水腫，造成次級腦損傷[41-42]。因此，可以通過減輕炎癥反應(yīng)減小腦水腫體積，從而治療顱內(nèi)出血。顱內(nèi)動(dòng)脈的病理性擴(kuò)張可形成顱內(nèi)動(dòng)脈瘤，其破裂可導(dǎo)致蛛網(wǎng)膜下腔出血，嚴(yán)重時(shí)可危及生命[43]。顱內(nèi)動(dòng)脈瘤的病因十分復(fù)雜，有研究認(rèn)為免疫反應(yīng)導(dǎo)致的血管炎癥及血管重構(gòu)為顱內(nèi)動(dòng)脈瘤產(chǎn)生及其破裂的主要原因[44]。研究證實(shí)，顱內(nèi)出血誘導(dǎo)的炎癥反應(yīng)中也有miRNA的參與。

2.1 參與調(diào)節(jié)顱內(nèi)出血過程中免疫反應(yīng)的miRNA 顱內(nèi)出血后，NLRP3炎癥小體可參與誘導(dǎo)炎癥反應(yīng)[45]，miR-223可以通過轉(zhuǎn)錄后調(diào)控機(jī)制抑制NLRP3的表達(dá)，減輕炎癥反應(yīng)，改善腦水腫[46]。miRNA let-7也參與調(diào)控腦出血后的炎癥反應(yīng)，應(yīng)用大鼠顱內(nèi)注射VII型細(xì)菌膠原酶誘導(dǎo)腦出血模型，發(fā)現(xiàn)腦出血可導(dǎo)致基底節(jié)區(qū)let-7c水平升高，且腦出血后立即經(jīng)鼻應(yīng)用let-7c拮抗劑可減少中性粒細(xì)胞浸潤及細(xì)胞凋亡[47]。Let-7c促進(jìn)炎癥反應(yīng)的機(jī)制尚不明確，let-7c可減少胰島素樣生長因子1受體(insulin-like growth factor 1 receptor，IGF1R)的表達(dá)，IGF1R可通過減少炎癥細(xì)胞向血腫周邊聚集而減輕炎癥反應(yīng)[48]。此外，let-7還可通過靶向其它免疫因子發(fā)揮對于神經(jīng)元的調(diào)控作用。近期研究發(fā)現(xiàn)，let-7b可通過與神經(jīng)元壞死時(shí)釋放的某些蛋白結(jié)合形成復(fù)合物后與TLR7結(jié)合，抑制表達(dá)于神經(jīng)元的TLR7，從而導(dǎo)致軸突損傷以及神經(jīng)元死亡[49]。

顱內(nèi)出血患者血漿中有30余種miRNA水平升高，應(yīng)用生物信息學(xué)軟件分析發(fā)現(xiàn)這些升高的miRNA大多與炎癥反應(yīng)有關(guān)，且這些miRNA大多數(shù)來源于炎癥細(xì)胞，如miR-150、miR-365、miR-30c、miR-27a、miR-574-5p、miR-130a及miR-423[50-51]。健康人血液中的miRNA多存在于由膜性結(jié)構(gòu)形成的微囊內(nèi)，以防止其降解，而顱內(nèi)出血患者血液中的miRNA既存在于微囊內(nèi)也存在于上清中，這可能是由于顱內(nèi)出血患者呈現(xiàn)全身性炎癥反應(yīng)，炎癥細(xì)胞增多導(dǎo)致血液中微囊增多進(jìn)而釋放更多的miRNA，也可能由于顱內(nèi)出血導(dǎo)致被機(jī)械破壞的血管及神經(jīng)元增多[12]，導(dǎo)致miRNA的釋放增多。

2.2 參與調(diào)節(jié)顱內(nèi)動(dòng)脈瘤誘導(dǎo)免疫反應(yīng)的miRNA 應(yīng)用高通量篩查發(fā)現(xiàn)顱內(nèi)動(dòng)脈瘤可誘導(dǎo)多種mi-RNA水平的改變，針對這些miRNA及與顱內(nèi)動(dòng)脈瘤病理生理相關(guān)的mRNA應(yīng)用生物信息學(xué)軟件進(jìn)行分析，發(fā)現(xiàn)這些miRNA與炎癥、平滑肌細(xì)胞增殖、程序性細(xì)胞死亡及氧化應(yīng)激等相關(guān)[52]。在所有差異表達(dá)的miRNA中，miR-21的上調(diào)最為明顯，其可上調(diào)16.97倍[52]。miR-21在顱內(nèi)動(dòng)脈瘤中的作用尚不明確，在巨噬細(xì)胞中，miR-21可參與調(diào)節(jié)免疫反應(yīng)。巨噬細(xì)胞內(nèi)轉(zhuǎn)染miR-21可以通過下調(diào)TLR4抑制NF-κB信號(hào)通路，減少LPS導(dǎo)致的炎癥因子IL-6釋放，增加抗炎因子IL-10表達(dá)，減少LPS誘導(dǎo)巨噬細(xì)胞導(dǎo)致的動(dòng)脈硬化斑塊形成[53]。miR-21在顱內(nèi)動(dòng)脈瘤及其它腦血管病中的作用尚需進(jìn)一步研究。在顱內(nèi)動(dòng)脈瘤導(dǎo)致蛛網(wǎng)膜下腔出血的患者腦脊液中發(fā)現(xiàn)miRNA-92a及miRNA-let7b水平的增高[54]，盡管這2種miRNA是否直接參與調(diào)節(jié)動(dòng)脈瘤導(dǎo)致蛛網(wǎng)膜下腔出血誘導(dǎo)的免疫反應(yīng)尚不明確，由于研究已經(jīng)證實(shí)miRNA-92a與巨噬細(xì)胞炎癥反應(yīng)密切相關(guān)[55]，而miRNA-let7的免疫調(diào)節(jié)作用也已在前文闡述，因而我們推測，這2種miRNA很可能參與調(diào)節(jié)顱內(nèi)動(dòng)脈瘤導(dǎo)致蛛網(wǎng)膜下腔出血過程中產(chǎn)生的免疫反應(yīng)。

腦血管病引發(fā)的免疫反應(yīng)參與腦血管病的發(fā)生、發(fā)展及預(yù)后過程，已引起研究者的廣泛關(guān)注。miRNA為一類新近發(fā)現(xiàn)的可以調(diào)控蛋白合成的調(diào)節(jié)子，可在腦血管病及免疫反應(yīng)中發(fā)揮重要作用。一種miRNA可同時(shí)調(diào)節(jié)多個(gè)生物過程且可在轉(zhuǎn)錄后水平快速調(diào)節(jié)基因表達(dá)，因而通過干擾某種miRNA的表達(dá)來治療腦血管病所致免疫反應(yīng)比靶向單一基因的治療措施具有更高的臨床應(yīng)用價(jià)值。動(dòng)物研究中已證實(shí)可通過靶向某種免疫反應(yīng)相關(guān)的miRNA實(shí)現(xiàn)治療腦血管病的目的[22]，而應(yīng)用某些miRNA的類似物或抑制物治療肝臟疾病已被應(yīng)用于臨床，為miRNA應(yīng)用于治療腦血管病奠定了基礎(chǔ)。然而想要實(shí)現(xiàn)將miRNA應(yīng)用于腦血管病的臨床治療仍有許多難點(diǎn)需要解決。首先，由于血腦屏障的存在導(dǎo)致藥物很難從外周血順利進(jìn)入腦內(nèi)，而側(cè)腦室注射又很難被患者接受，因而miRNA的給藥途徑仍需進(jìn)一步探索。其次，由于腦血管病患者病情常常千變?nèi)f化，因而很難確定合適的給藥時(shí)間。最后，miRNA的選擇也存在困難，由于一種miRNA常常有多個(gè)作用靶點(diǎn)，盲目應(yīng)用miRNA可能會(huì)對機(jī)體產(chǎn)生其它不利影響，因而，miRNA的臨床應(yīng)用必須在確切了解其靶點(diǎn)及功能的基礎(chǔ)上慎重選擇。

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(責(zé)任編輯： 盧 萍， 羅 森)

Progress in study of immune response regulated by microRNAs in process of ischemic and hemorrhagic cerebrovascular diseases

WANG Jue1,2, ZHAO Hai-ping1

(1CerebrovascularDiseasesInstituteandDepartmentofNeurology,XuanwuHospitalofCapitalMedicalUniversity,Beijing100053,China;2DepartmentofNeurology,ShengjingHospital,AffiliatedHospitalofChinaMedicalUniversity,Shenyang110004,China.E-mail:zhaohaiping@xwh.ccmu.edu.cn)

Immune response is one of the main reasons causing neurological deficits in the patients with cerebrovascular diseases, which activates microglia, induces inflammatory reaction and finally results in serious neuronal and endothelial injury. MicroRNAs take part in the regulation of immunoreaction, and simultaneously regulates many target genes and induces faster post-transcriptional regulation to its target genes compared with the traditional transcriptional regulation. For providing a basis for the clinical use of microRNAs and applying new therapy, this review mainly focuses on the function and mechanism of microRNAs in the regulation of the immunoreaction caused by cerebrovascular diseases.

腦血管??； 免疫反應(yīng)； 微小RNA

Cerebrovascular diseases; Immunoreaction; MicroRNAs

1000- 4718(2017)02- 0369- 06

2016- 07- 20

2016- 09- 09

國家自然科學(xué)基金資助項(xiàng)目(No. 81571280； No. 81271461)

R363

A

10.3969/j.issn.1000- 4718.2017.02.030

雜志網(wǎng)址： http://www.cjpp.net

△通訊作者 Tel: 010-83199236; E-mail: zhaohaiping@xwh.ccmu.edu.cn