吳孝軍，朱路文，李宏玉，唐強(qiáng)

運(yùn)動(dòng)預(yù)處理誘導(dǎo)腦缺血耐受機(jī)制的研究進(jìn)展①

吳孝軍1，朱路文2，李宏玉1，唐強(qiáng)2

運(yùn)動(dòng)預(yù)處理可誘導(dǎo)腦缺血性損傷耐受，具有顯著的腦神經(jīng)系統(tǒng)保護(hù)作用。運(yùn)動(dòng)預(yù)處理改善腦缺血性損傷的具體作用機(jī)制較為復(fù)雜，涉及多靶點(diǎn)、多途徑的調(diào)控，其中抑制細(xì)胞凋亡、促進(jìn)腦神經(jīng)血管生成、抑制谷氨酸的過(guò)度激活以及調(diào)控炎癥反應(yīng)是運(yùn)動(dòng)預(yù)處理誘導(dǎo)腦缺血耐受的關(guān)鍵機(jī)制。然而運(yùn)動(dòng)預(yù)處理誘導(dǎo)腦缺血耐受的機(jī)制遠(yuǎn)不止于此，有待進(jìn)一步研究和發(fā)現(xiàn)。

腦缺血；耐受；運(yùn)動(dòng)預(yù)處理；綜述

[本文著錄格式]吳孝軍，朱路文，李宏玉，等.運(yùn)動(dòng)預(yù)處理誘導(dǎo)腦缺血耐受機(jī)制的研究進(jìn)展[J].中國(guó)康復(fù)理論與實(shí)踐,2015, 21(6):657-661.

CITED AS:Wu XJ,Zhu LW,Li HY,et al.Advance in mechanism of cerebral ischemia tolerance induced by exercise preconditioning (review)[J].Zhongguo Kangfu Lilun Yu Shijian,2015,21(6):657-661.

腦血管病(cerebrovascular disease,CVD)占我國(guó)最常見(jiàn)致殘和致死原因的第二位[1]，其中以腦血管阻塞性缺血所致的缺血性腦卒中最為常見(jiàn)，發(fā)病率約占腦卒中的70%[2]。尋找有效的防治手段，以減小腦缺血損傷后腦組織梗死的面積，成為預(yù)防醫(yī)學(xué)和臨床醫(yī)學(xué)的研究熱點(diǎn)。

運(yùn)動(dòng)預(yù)處理(exercise preconditioning,EP)，即在腦缺血前給予多次相同的運(yùn)動(dòng)訓(xùn)練，可有效誘導(dǎo)腦缺血耐受，產(chǎn)生明顯腦神經(jīng)系統(tǒng)保護(hù)作用，并減緩因腦缺血引發(fā)的一系列腦組織損傷[3]。相比于其他預(yù)處理方式，其優(yōu)勢(shì)在于便于掌握，易被患者接受，臨床上便于操作。目前研究普遍認(rèn)為運(yùn)動(dòng)預(yù)處理是與多個(gè)通道、多個(gè)水平、多個(gè)靶點(diǎn)密切相關(guān)的綜合性系統(tǒng)。

1 神經(jīng)元凋亡

缺血損傷后腦神經(jīng)細(xì)胞的損傷表現(xiàn)為兩種方式，一種是由于嚴(yán)重的腦組織損傷而導(dǎo)致的直接性病理死亡，而另一種則是細(xì)胞程序性凋亡(programmed cell death,PCD)，也就是所謂的細(xì)胞生理性死亡，是由于細(xì)胞內(nèi)部自殺程序在內(nèi)外界因素的刺激下被激活而導(dǎo)致的。細(xì)胞凋亡在腦組織缺血性損傷中，尤其是腦缺血再灌注性損傷中發(fā)揮著關(guān)鍵性作用[4-6]。腦缺血損傷發(fā)生后的遲發(fā)性神經(jīng)元死亡以凋亡為主[7]。如果能及時(shí)有效地阻止神經(jīng)元凋亡的發(fā)生發(fā)展，可以有效減輕由于腦缺血造成的腦組織損傷。

Tahamtan等發(fā)現(xiàn)運(yùn)動(dòng)預(yù)處理使缺血性損傷的腦組織海馬區(qū)保留更多存活的神經(jīng)元，有效減少神經(jīng)元凋亡[8]。Zhang等研究指出運(yùn)動(dòng)訓(xùn)練有效緩解腦卒中后自噬現(xiàn)象，并降低神經(jīng)細(xì)胞凋亡[9]。Chaudhry等研究表明運(yùn)動(dòng)訓(xùn)練誘發(fā)的神經(jīng)保護(hù)可能是通過(guò)調(diào)節(jié)基質(zhì)金屬蛋白酶-9(matrix metalloprotein-9,MMP-9)和細(xì)胞外調(diào)節(jié)蛋白激酶(extracellular regulated protein kinases 1/2, ERK1/2)的表達(dá)，以減少神經(jīng)細(xì)胞凋亡而實(shí)現(xiàn)的[10]。Liebelt等

發(fā)現(xiàn)運(yùn)動(dòng)預(yù)處理可以通過(guò)調(diào)控?zé)嵝菘说鞍?0(heat shock protein-70,HSP-70)和磷酸化ERK1/2的表達(dá)，減輕腦缺血/再灌注損傷[11]，ERK和HSP-70的抑制劑可同時(shí)使運(yùn)動(dòng)預(yù)處理產(chǎn)生的腦保護(hù)作用消失。磷酸化ERK1/2抑制劑可以有效減少腦組織受損，但不能導(dǎo)致HSP-70蛋白表達(dá)降低。這個(gè)現(xiàn)象表明，在運(yùn)動(dòng)預(yù)處理后的缺血性腦損傷中，HSP-70并非ERK1/2的下游調(diào)節(jié)蛋白。之前已有研究表明，HSP-70可通過(guò)抑制細(xì)胞凋亡誘導(dǎo)因子(apoptosis-inducing factor,AIF)并促進(jìn)抗凋亡蛋白B淋巴細(xì)胞瘤-2基因(B-cell lymphoma-2,Bcl-2)家族，產(chǎn)生抗細(xì)胞凋亡作用[12]。ERK介導(dǎo)的信號(hào)通路在缺血誘導(dǎo)的細(xì)胞凋亡過(guò)程中發(fā)揮重要作用，可能與調(diào)節(jié)Bcl-2相關(guān)X蛋白(Bcl-2 associated x protein,Bax)蛋白/Bcl-2蛋白的表達(dá)有關(guān)[13-14]。運(yùn)動(dòng)預(yù)處理影響B(tài)cl-2和Bax蛋白表達(dá)產(chǎn)生腦保護(hù)作用的機(jī)制與低氧預(yù)處理的機(jī)制相類(lèi)似，Bcl-2和Bax分別是調(diào)控神經(jīng)元凋亡分子家族中的核心成員[15]。王璐等也認(rèn)為運(yùn)動(dòng)預(yù)處理能減少力竭運(yùn)動(dòng)誘導(dǎo)的大鼠大腦皮質(zhì)細(xì)胞凋亡，產(chǎn)生腦細(xì)胞保護(hù)作用，其對(duì)細(xì)胞凋亡的調(diào)控作用可能是通過(guò)影響B(tài)cl-2和Bax蛋白表達(dá)而實(shí)現(xiàn)的[16]。Cho和Ji等認(rèn)為，原位末端轉(zhuǎn)移酶標(biāo)記技術(shù)(TdT-mediated dUTP Nick-End Labeling,TUNEL)中顯示的陽(yáng)性細(xì)胞代表凋亡細(xì)胞，其中半胱胺酸蛋白酶蛋白-3(caspase-3)是細(xì)胞凋亡的主要執(zhí)行者之一[17-18]。Choi等研究發(fā)現(xiàn)短期跑步鍛煉抑制缺氧缺血性損傷所誘導(dǎo)的DNA分裂，有效降低caspase-3的表達(dá)，從而對(duì)腦組織細(xì)胞凋亡產(chǎn)生抑制作用[19]。Zhang等也發(fā)現(xiàn)運(yùn)動(dòng)預(yù)處理可減小缺血性腦損傷腦梗死體積，減少神經(jīng)元凋亡，產(chǎn)生神經(jīng)保護(hù)作用，其機(jī)制可能與抑制caspase-3和上調(diào)Bcl-2的表達(dá)有關(guān)[20]。Zhao等還發(fā)現(xiàn)運(yùn)動(dòng)訓(xùn)練降低細(xì)胞色素C和AIF的釋放，減少AIF遷移至細(xì)胞核并抑制caspases激活，從而阻斷關(guān)鍵的細(xì)胞凋亡途徑[21]。我們可以認(rèn)為，運(yùn)動(dòng)預(yù)處理可以通過(guò)增加ERK 1/2和HSP-70的表達(dá)誘發(fā)腦缺血耐受，其中細(xì)胞凋亡誘導(dǎo)因子和抗凋亡蛋白發(fā)揮著重要作用。

2 腦血管生成及神經(jīng)再生

運(yùn)動(dòng)預(yù)處理通過(guò)多種機(jī)制誘導(dǎo)腦缺血耐受，包括促進(jìn)神經(jīng)血管生成和血管內(nèi)皮生長(zhǎng)因子(vascular endothelial growth factor,VEGF)的表達(dá)[3]。Thomas等在動(dòng)物實(shí)驗(yàn)中發(fā)現(xiàn)跑步訓(xùn)練可刺激血管生成和神經(jīng)再生[22]。磁共振腦血管成像(magnetic resonance angiography,MRA)可以有效檢測(cè)腦血管發(fā)生的細(xì)微變化。Bullitt研究發(fā)現(xiàn)健康受試者在運(yùn)動(dòng)訓(xùn)練以后，使用MRA檢測(cè)腦血管的情況時(shí)發(fā)現(xiàn)微血管數(shù)量發(fā)生變化[23]。Isaacs等認(rèn)為較大強(qiáng)度的運(yùn)動(dòng)預(yù)處理導(dǎo)致中年雌性大鼠小腦中毛細(xì)血管的密度明顯增加[24]；同時(shí)運(yùn)動(dòng)訓(xùn)練也能提高大鼠腦皮質(zhì)運(yùn)動(dòng)區(qū)的血管新生并增強(qiáng)中年大鼠紋狀體腦血管的完整性[25-27]。此外，Hu等發(fā)現(xiàn)7～14 d的運(yùn)動(dòng)活動(dòng)可以提高微血管生成重要標(biāo)志物CD31的表達(dá)[28]。Rhyu等在動(dòng)物實(shí)驗(yàn)中發(fā)現(xiàn)適當(dāng)?shù)倪\(yùn)動(dòng)訓(xùn)練導(dǎo)致猴腦皮質(zhì)血管密度增加，但在運(yùn)動(dòng)結(jié)束后3個(gè)月時(shí)血管密度又回到訓(xùn)練前水平，說(shuō)明持續(xù)的運(yùn)動(dòng)訓(xùn)練才能發(fā)揮腦保護(hù)作用[29]。Zwagerman等認(rèn)為運(yùn)動(dòng)預(yù)處理明顯增加大鼠短暫性腦缺血發(fā)作再灌注過(guò)程中腦血流量[30]。Zhang等研究表明運(yùn)動(dòng)訓(xùn)練增加腦缺血損傷后腦皮質(zhì)微血管密度，改善血液流動(dòng)能力，同時(shí)減少腦梗死體積，從而促進(jìn)神經(jīng)功能恢復(fù)[31]。這其中所涉及的血管生成過(guò)程可能與Tie-2、p-Akt蛋白的表達(dá)增加有關(guān)。Zhang等發(fā)現(xiàn)缺血前跑步機(jī)訓(xùn)練可以通過(guò)調(diào)節(jié)腦血流量(cerebral blood flow,CBF)和內(nèi)皮素-1(endothelin-1,ET-1)而防止缺血性腦組織損傷[32]。

VEGF在血管生成的過(guò)程中發(fā)揮著關(guān)鍵作用，運(yùn)動(dòng)預(yù)處理通過(guò)上調(diào)VEGF和腦源性神經(jīng)營(yíng)養(yǎng)因子(brain derived neurotrophic factor,BDNF)增加大鼠腦皮質(zhì)和紋狀體的血管密度[26]。Kang等研究指出運(yùn)動(dòng)預(yù)處理通過(guò)增加VEGF在運(yùn)動(dòng)皮層的表達(dá)來(lái)促進(jìn)微血管的完整性[33]。Matsuda等認(rèn)為局部缺血后運(yùn)動(dòng)預(yù)處理可上調(diào)中期因子(midkine,MK)、血小板內(nèi)皮細(xì)胞黏附分子1(platelet endothelial cell adhesion molecule-1,PECAM-1)和神經(jīng)生長(zhǎng)因子，以改善梗死區(qū)周?chē)难苌蒣34]。Ma等研究指出運(yùn)動(dòng)預(yù)處理有效增加VEGF和基質(zhì)后金屬基質(zhì)蛋白酶-2(matrix metalloprotein-2,MMP-2)的基因和蛋白表達(dá)[35]。此外，運(yùn)動(dòng)預(yù)處理提高了胰島素樣生長(zhǎng)因子(insulin-like growth factors,IGF)的表達(dá)，其與神經(jīng)、血管生成密切相關(guān)[36-37]。Lee等發(fā)現(xiàn)腦缺血后促血管生成素(angiopoietins,Ang)及其受體Tie-2構(gòu)成的Ang/ Tie-2系統(tǒng)在血管新生中發(fā)揮了關(guān)鍵性作用[38]。研究還發(fā)現(xiàn)適當(dāng)強(qiáng)度的運(yùn)動(dòng)訓(xùn)練在急性腦缺血病發(fā)生后導(dǎo)致腦梗死體積減小，同時(shí)增加腦缺血區(qū)周?chē)难苊芏?。這一機(jī)制可能與促進(jìn)Ang-1、Tie-2以及其下游磷脂酰肌醇3激酶(Phosphatidylinositol 3-kinase,PI3K)/蛋白激酶B(protein kinase B,PKB，也稱(chēng)為Serine/threonine Kinase,Akt)的表達(dá)有關(guān)。

BDNF在增加突觸可塑性和促進(jìn)神經(jīng)再生方面發(fā)揮著重要作用。Thomas等研究指出運(yùn)動(dòng)訓(xùn)練提高包括BDNF在內(nèi)的多種生長(zhǎng)因子表達(dá)水平，對(duì)于細(xì)胞存活、神經(jīng)突生長(zhǎng)，以及其他形式的神經(jīng)再生具有重要意義[22]。Padilla等發(fā)現(xiàn)跑步訓(xùn)練調(diào)節(jié)BDNF和突觸蛋白I的mRNA表達(dá)，促進(jìn)腦卒中患者更好地恢復(fù)[39]。Liu等研究表明運(yùn)動(dòng)訓(xùn)練促進(jìn)線(xiàn)粒體功能，增加BDNF和腦抗氧化酶的表達(dá)，從而保持腦能量代謝穩(wěn)定[40]。Yang等研究發(fā)現(xiàn)主動(dòng)運(yùn)動(dòng)訓(xùn)練顯著增加BDNF的表達(dá)，后者通過(guò)上調(diào)小鼠大腦皮層和海馬區(qū)DNA修復(fù)的酶脫嘌呤/脫嘧啶核酸內(nèi)切酶-1(Apurinic/apyrimidinic endonuclease-1,APE1)的表達(dá)，以增強(qiáng)DNA的修復(fù)，減輕神經(jīng)元損傷[41]。神經(jīng)營(yíng)養(yǎng)蛋白4(Neurotrophin-4,NT-4)屬于神經(jīng)營(yíng)養(yǎng)因子家族，與BDNF相類(lèi)似，都具有腦保護(hù)作用。Chung等發(fā)現(xiàn)跑步機(jī)訓(xùn)練改變了NT-4及其受體trkB的表達(dá)，減輕大鼠缺血性腦損壞程度[42]。Zheng等研究表明運(yùn)動(dòng)訓(xùn)練直接影響神經(jīng)功能恢復(fù)，這一過(guò)程與激活I(lǐng)GF-1/ Akt信號(hào)通路導(dǎo)致神經(jīng)祖細(xì)胞數(shù)量增加有關(guān)[43]。Zhang等研究表明運(yùn)動(dòng)預(yù)處理增加梗死區(qū)周?chē)鶬GF-1的表達(dá)及細(xì)胞增殖，促進(jìn)腦缺血后神經(jīng)再生[31]。我們歸納認(rèn)為，運(yùn)動(dòng)預(yù)處理通過(guò)調(diào)整一系列相關(guān)蛋白的表達(dá)，促進(jìn)腦神經(jīng)血管再生，同時(shí)增加腦血流量，從而發(fā)揮腦神經(jīng)保護(hù)作用，保持神經(jīng)血管單元的完整性。

3 谷氨酸興奮性毒性

缺血性腦卒中后谷氨酸的過(guò)量釋放加重腦組織損傷程

度[44]。Danbolt等認(rèn)為谷氨酸轉(zhuǎn)運(yùn)體1(Glutamate transporter-1, GLT-1)在去除腦組織谷氨酸時(shí)發(fā)揮最重要的作用[45]。Yang等發(fā)現(xiàn)運(yùn)動(dòng)預(yù)處理上調(diào)腦缺血后GLT-1的表達(dá)，減少細(xì)胞外谷氨酸濃度，降低腦梗死體積和改善神經(jīng)功能[46]。Kalandadze等發(fā)現(xiàn)蛋白激酶C(protein kinase C,PKC)的激活可降低細(xì)胞表面GLT-1的表達(dá)，這可能會(huì)抑制細(xì)胞外谷氨酸的消除[47]。此外，P13K/ Akt通路也參與這一保護(hù)機(jī)制[48]。

Zhang等認(rèn)為缺血前運(yùn)動(dòng)預(yù)處理可以抑制谷氨酸過(guò)度釋放，這可能會(huì)涉及事件相關(guān)激酶ERK1/2的變化[49]。Wang等研究表明運(yùn)動(dòng)預(yù)處理通過(guò)調(diào)節(jié)興奮性氨基酸轉(zhuǎn)運(yùn)蛋白2(excitatory amino acid transporters 2,EAAT-2)和ERK1/2的表達(dá)，誘導(dǎo)腦缺血耐受[50]。Zhang等的研究還發(fā)現(xiàn)運(yùn)動(dòng)預(yù)處理能抑制谷氨酸受體的表達(dá)，如代謝型谷氨酸受體5(metabotropic glutamate receptors 5,mGluR5)和N-甲基-D-天冬氨酸受體亞基2B型(N-methyl-D-aspartate receptor 2B subunit,NR2B)，減輕谷氨酸過(guò)度釋放的神經(jīng)毒性[51]。Wang等認(rèn)為運(yùn)動(dòng)預(yù)處理可以通過(guò)上調(diào)GLT-1表達(dá)促進(jìn)缺血性損傷后谷氨酸的攝取，抑制NR2B和mGluR5的表達(dá)水平，以減少谷氨酸興奮性毒性，這可能涉及兩條信號(hào)通路：PKC-A-GLT-1-谷氨酸和PI3K/Akt信號(hào)-GLT-1-谷氨酸[52]。因此，運(yùn)動(dòng)預(yù)處理可以通過(guò)調(diào)節(jié)谷氨酸系統(tǒng)的興奮性毒性誘導(dǎo)腦缺血耐受。

4 炎癥反應(yīng)

腦缺血性損傷可迅速引發(fā)缺血后的炎癥反應(yīng)。正常的炎癥反應(yīng)可以有效地減少進(jìn)入機(jī)體的病原微生物，以此來(lái)保持我們的機(jī)體健康；但是炎癥反應(yīng)的過(guò)度活化進(jìn)一步加重腦組織的損傷。Jander等發(fā)現(xiàn)炎癥介質(zhì)在保護(hù)性預(yù)處理過(guò)程中發(fā)揮著明顯作用，成為缺血性腦卒中后防治的重要靶點(diǎn)[53]。

Wang等研究表明炎癥反應(yīng)在急性缺血性腦卒中中發(fā)揮重要作用，神經(jīng)元損傷加重白細(xì)胞浸潤(rùn)、微血管損傷和自由基的產(chǎn)生[54]。Berti等認(rèn)為許多炎性細(xì)胞因子如腫瘤壞死因子α(tumor necrosis factor-α,TNF-α)、白細(xì)胞介素1β(interleukin-1β, IL-1β)和白細(xì)胞介素6(interleukin-6,IL-6)，都參與缺血性腦卒中后的炎癥反應(yīng)[55]。Park等發(fā)現(xiàn)運(yùn)動(dòng)預(yù)處理通過(guò)調(diào)節(jié)TNF-α和IL-1β可部分阻止沙鼠腦缺血后海馬神經(jīng)元凋亡[56]。Ding等認(rèn)為運(yùn)動(dòng)預(yù)處理可以通過(guò)降低炎癥介質(zhì)的表達(dá)和引起白細(xì)胞的積聚，降低腦缺血/再灌注損傷[57]。運(yùn)動(dòng)預(yù)處理可以有效降低腦缺血區(qū)皮層上TNF-α受體表達(dá)，這一結(jié)論表明TNF-α參與多次重復(fù)運(yùn)動(dòng)預(yù)處理誘導(dǎo)的腦缺血耐受[58]。Laflamme等研究表明，Toll樣受體4(toll like receptor 4,TLR4)在中樞神經(jīng)系統(tǒng)內(nèi)的表達(dá)是其介導(dǎo)腦缺血后炎癥反應(yīng)的基礎(chǔ)[59]。腦缺血前的運(yùn)動(dòng)預(yù)處理可以有效下調(diào)TLR4的表達(dá)，降低腦組織損傷[60]，降低其引發(fā)的炎性細(xì)胞因子級(jí)聯(lián)反應(yīng)[61]，通過(guò)下調(diào)TLR2和TLR4抑制核因子-kB(nuclear factor-kB,NF-kB)和髓樣分化因子(myeloiddifferentiationfactor88,MyD88)的過(guò)度表達(dá)[62]，從而減輕腦缺血損傷中白細(xì)胞遷移、滲透和積累。

最新相關(guān)研究表明，腦缺血再灌注后24 h，在運(yùn)動(dòng)預(yù)處理組血清中TNF-α、IL-1β及IL-6的含量均顯著降低，腦缺血區(qū)域皮質(zhì)的病理性損傷明顯減輕，神經(jīng)功能得到明顯改善。這表明運(yùn)動(dòng)預(yù)處理可降低腦缺血再灌注損傷過(guò)程中與炎癥反應(yīng)相關(guān)因子的濃度，有效抑制由于炎癥所引起的級(jí)聯(lián)反應(yīng)，因而減輕腦缺血再灌注后腦組織的損傷，發(fā)揮腦神經(jīng)系統(tǒng)保護(hù)作用[63]。

5小結(jié)

綜上所述，運(yùn)動(dòng)預(yù)處理通過(guò)抑制神經(jīng)細(xì)胞凋亡，促進(jìn)神經(jīng)血管再生，抑制谷氨酸過(guò)度釋放，減輕炎癥反應(yīng)，以誘導(dǎo)腦缺血耐受。未來(lái)很可能會(huì)更多通過(guò)分子機(jī)制層面來(lái)探討這一耐受機(jī)制。無(wú)論以什么樣的方法和形式來(lái)闡明運(yùn)動(dòng)預(yù)處理誘導(dǎo)腦缺血耐受的機(jī)制都將有利于提高人們對(duì)缺血性腦損傷的認(rèn)識(shí)，為運(yùn)動(dòng)訓(xùn)練作為缺血性腦卒中的有效防治措施提供堅(jiān)實(shí)的理論基礎(chǔ)，鼓勵(lì)具有腦卒中危險(xiǎn)因素的患者積極參加各種運(yùn)動(dòng)項(xiàng)目。

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Advance in Mechanism of Cerebral Ischemia Tolerance Induced by Exercise Preconditioning(review)

WU Xiao-jun1,ZHU Lu-wen2,LI Hong-yu1,TANG Qiang2
1.Heilongjiang University of Chinese Medicine,Harbin,Heilongjiang 150040,China;2.The Second Hospital Affiliated to Heilongjiang University of Chinese Medicine,Harbin,Heilongjiang 150001,China

Cerebral ischemia tolerance was induced by exercise preconditioning,which protected the brain from injury.The detailed mechanism of exercise preconditioning protecting cerebral ischemia injury was complicated,which involving the regulation of multiple target point and multi-path,such as inhibiting cell apoptosis,promoting angiogenesis in the brain,inhibiting the excessive activation of glutamic acid as well as the regulation of inflammation.More mechanisms were still unknown.

cerebral ischemia;tolerance;exercise preconditioning;review

10.3969/j.issn.1006-9771.2015.06.006

R743.3

A

1006-9771(2015)06-0657-05

2015-03-17

2015-04-20)

1.哈爾濱市科技創(chuàng)新人才專(zhuān)項(xiàng)基金(青年后備人)(No.2014RFQGJ150)；2.黑龍江中醫(yī)藥大學(xué)領(lǐng)軍人才計(jì)劃項(xiàng)目(No.2012RCL02)；3.黑龍江省高?？萍紕?chuàng)新團(tuán)隊(duì)計(jì)劃項(xiàng)目(No.2013TD007)。

1.黑龍江中醫(yī)藥大學(xué)，黑龍江哈爾濱市150040；2.黑龍江中醫(yī)藥大學(xué)附屬第二醫(yī)院，黑龍江哈爾濱市150001。作者簡(jiǎn)介：吳孝軍(1990-)，男，遼寧遼陽(yáng)市人，碩士研究生，主要研究方向：腦卒中中醫(yī)康復(fù)的基礎(chǔ)研究。通訊作者：唐強(qiáng)(1963-)，男，四川大竹縣人，博士，教授，主要研究方向：神經(jīng)系統(tǒng)疾病中醫(yī)康復(fù)基礎(chǔ)與臨床。E-mail:tangqiang1963@163.com。