电针结合天麻素对局灶性脑缺血大鼠神经功能、额叶皮质勿动蛋白A及其受体表达的影响
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摘要
目的:观察电针结合天麻素对局灶性脑缺血大鼠神经功能及缺血灶周围区额叶皮质勿动蛋白A(Nogo-A)及受体(NgR)表达的影响,探讨针药结合治疗脑缺血的部分神经再生机制。方法:SD大鼠随机分为正常组、模型组、电针组、天麻素组和电针+天麻素组,每组10只。采用线栓法复制局灶性脑缺血大鼠模型。电针组电针左侧"曲池"穴和"合谷"穴,刺激30min,每天1次,共治疗14d;天麻素组按10mg/kg剂量腹腔注射天麻素注射液,每天1次,共治疗14d;电针+天麻素组给予电针与天麻素治疗,每天1次,共治疗14d。观察大鼠治疗后神经功能恢复情况,免疫组织化学方法检测缺血灶周围区额叶皮质Nogo-A及NgR蛋白的表达。结果:电针组、天麻素组和电针+天麻素组神经功能评分低于模型组(P<0.05),电针+天麻素组神经功能评分低于电针组、天麻素组(P<0.05)。模型组Nogo-A及NgR的表达较正常组明显增强(P<0.05),电针组、天麻素组和电针+天麻素组Nogo-A及NgR的表达较模型组明显减弱(P<0.05),电针+天麻素组Nogo-A及NgR的表达较电针组或天麻素组明显减弱(P<0.05)。结论:电针与天麻素结合可下调缺血灶周围区额叶皮质Nogo-A及NgR的表达,改善神经功能,其作用优于单独电针或天麻素治疗。
Objective To observe the effect of electroacupuncture(EA)intervention combined with medication(Gastrodin)on changes of neurological function and expression of Nogo-A and Nogo-A receptor(NgR)in the frontal lobe cortex around the ischemic loci of focal cerebral ischemia(FCI)rats,so as to explore its mechanism underlying improvement of neuroregeneration of FCI.Methods Fifty male Sprague-Dawley rats were randomly divided into normal control,model,EA,medication and EA+medication groups(n=10in each group).The FCI model was induced by occlusion of the middle cerebral artery(MCAO)with thread embolus.EA was applied to the left"Quchi"(LI 11)and"Hegu"(LI 4)for 30 min,once daily for 14 days after MCAO.For rats of the medication group,Gastrodin(10mg/kg)was administrated by intraperitoneal injection,once daily for 14 days.The neurological impairment was assessed by Zea Longa's scoring.The expression of Nogo-A and NgR in the frontal lobe cortex around the ischemic loci was detected by immunohistochemistry.Results In comparison with the normal control group,cerebrocortical Nogo-A and NgR expression levels of the model group were significantly increased(P<0.05).Compared with the model group,the Zea Longa's score and Nogo-A and NgR expression levels were evidently down-regulated in the EA,medication and EA+medication groups(P<0.05).The Zea Longa's score and Nogo-A and NgR expression levels were significantly lower in the EA+medication group than in the EA and medication groups(P<0.05).Conclusion EA intervention and Gastrodin administration can down-regulate cerebro-cortical Nogo-A and NgR protein expression in FCI rats,which may contribute to their action in improving neurological impairment.The effect of EA+Gastrodin is better than simple EA or Gastrodin treatment.
Objective To observe the effect of electroacupuncture(EA)intervention combined with medication(Gastrodin)on changes of neurological function and expression of Nogo-A and Nogo-A receptor(NgR)in the frontal lobe cortex around the ischemic loci of focal cerebral ischemia(FCI)rats,so as to explore its mechanism underlying improvement of neuroregeneration of FCI.Methods Fifty male Sprague-Dawley rats were randomly divided into normal control,model,EA,medication and EA+medication groups(n=10in each group).The FCI model was induced by occlusion of the middle cerebral artery(MCAO)with thread embolus.EA was applied to the left"Quchi"(LI 11)and"Hegu"(LI 4)for 30 min,once daily for 14 days after MCAO.For rats of the medication group,Gastrodin(10mg/kg)was administrated by intraperitoneal injection,once daily for 14 days.The neurological impairment was assessed by Zea Longa's scoring.The expression of Nogo-A and NgR in the frontal lobe cortex around the ischemic loci was detected by immunohistochemistry.Results In comparison with the normal control group,cerebrocortical Nogo-A and NgR expression levels of the model group were significantly increased(P<0.05).Compared with the model group,the Zea Longa's score and Nogo-A and NgR expression levels were evidently down-regulated in the EA,medication and EA+medication groups(P<0.05).The Zea Longa's score and Nogo-A and NgR expression levels were significantly lower in the EA+medication group than in the EA and medication groups(P<0.05).Conclusion EA intervention and Gastrodin administration can down-regulate cerebro-cortical Nogo-A and NgR protein expression in FCI rats,which may contribute to their action in improving neurological impairment.The effect of EA+Gastrodin is better than simple EA or Gastrodin treatment.
引文
[1]Cheatwood J L,Emerick A J,Schwab M E,et al.Nogo-A expression after focal ischemic stroke in the adult rat[J].Stroke,2008,39(7):2091-2098.
[2]Zhang Q W,Deng X X,Sun X,et al.Exercise promotes axon regeneration of newborn striatonigral and corticonigral projection neurons in rats after ischemic stroke[J].PLoS One,2013,8(11):e 80139.
[3]Kilic E,ElAli A,Kilic U,et al.Role of Nogo-A in neuronal survival in the reperfused ischemic brain[J].J Cereb Blood Flow Metab,2010,30(5):969-984.
[4]伍芳,龚标,李学智,等.电针对局灶性脑梗死大鼠Nogo-A及其受体NgR和运动诱发电位的影响[J].第三军医大学学报,2013,35(3):228-232.
[5]韩永升,徐银,韩咏竹,等.电针对局灶性脑缺血再灌注大鼠神经血管单元的保护作用[J].针刺研究,2013,38(3):173-180.
[6]张洪,周敏,周平.天麻素注射液治疗急性脑梗死的临床研究[J].中西医结合心脑血管病杂志,2010,8(4):427-429.
[7]Zea Longa E L,Weinstein P R,Carlson S,et al.Reversible middle cerebral artery occlusion without craniectomy in rats[J].Stroke,1989,20(1):84-91.
[8]缪化春,吴锋,丁见,等.电针联合天麻多糖对脑缺血大鼠齿状回神经干细胞巢蛋白和干细胞因子表达的影响[J].针刺研究,2014,39(1):40-45.
[9]吴中亮,任宁.天麻素注射液对大鼠脑缺血再灌注损伤细胞凋亡的影响[J].解放军医药学学报,2008,24(3):204-207.
[10]Sun L,Qiang R,Yang Y,et al.L-serine treatment may improve neurorestoration of rats after permanent focal cerebral ischemia potentially through improvement of neurorepair[J].PLoS One,2014,9(3):e 93405.
[11]Lee J K,Kim J E,Sivula M,et al.Nogo receptor antagonism promotes stroke recovery by enhancing axonal plasticity[J].J Neurosci,2004,24(27):6209-6217.
[12]蔡玉颖,刘志顺,王顺,等.电针曲池、足三里穴对脑缺血再灌注损伤大鼠神经功能缺损的影响[J].上海中医药大学学报,2009,23(6):64-66.
[13]王可博,庞国军,方智松.针刺合谷透后溪治疗中风偏瘫后手指拘挛127例[J].上海针灸杂志,2008,27(1):35.
[14]邬伟魁,张海燕,宋伟,等.以勿动蛋白-A及其受体为靶点的促神经再生中药研究[J].中国实验方剂学杂志,2012,18(1):239-242.
[15]Qin X D,Kang L Y,Liu Y,et al.Chinese medicine’s intervention effect on Nogo-A/NgR[J].Evid Based Complement Alternat Med,2012,2012:528482.
[16]王彤宇.天麻素注射液对急性脑梗死的神经保护作用[J].天津医药,2011,39(3):205-207.
[17]王德伟,刘黎青,周盛.针药结合对实验性脑缺血作用机制的研究进展[J].山东中医杂志,2009,28(12):881-882.
[18]魏彦珍,刘轲,张怀亮.针药结合治疗脑梗死机制研究进展[J].辽宁中医药大学学报,2014,16(2):217-219.
[19]崔晶晶,高俊虹,王玉敏,等.针药结合增效机制研究的新思路探讨[J].针刺研究,2010,35(2):146-149.
[20]刘炜,刘丽星,史晓伟,等.三七总皂苷对局灶性脑梗死大鼠海马CA 1区Nogo-A/NgR 1/RhoA信号通路蛋白表达的影响[J].中西医结合心脑血管病杂志,2014,12(11):1370-1373.
[2]Zhang Q W,Deng X X,Sun X,et al.Exercise promotes axon regeneration of newborn striatonigral and corticonigral projection neurons in rats after ischemic stroke[J].PLoS One,2013,8(11):e 80139.
[3]Kilic E,ElAli A,Kilic U,et al.Role of Nogo-A in neuronal survival in the reperfused ischemic brain[J].J Cereb Blood Flow Metab,2010,30(5):969-984.
[4]伍芳,龚标,李学智,等.电针对局灶性脑梗死大鼠Nogo-A及其受体NgR和运动诱发电位的影响[J].第三军医大学学报,2013,35(3):228-232.
[5]韩永升,徐银,韩咏竹,等.电针对局灶性脑缺血再灌注大鼠神经血管单元的保护作用[J].针刺研究,2013,38(3):173-180.
[6]张洪,周敏,周平.天麻素注射液治疗急性脑梗死的临床研究[J].中西医结合心脑血管病杂志,2010,8(4):427-429.
[7]Zea Longa E L,Weinstein P R,Carlson S,et al.Reversible middle cerebral artery occlusion without craniectomy in rats[J].Stroke,1989,20(1):84-91.
[8]缪化春,吴锋,丁见,等.电针联合天麻多糖对脑缺血大鼠齿状回神经干细胞巢蛋白和干细胞因子表达的影响[J].针刺研究,2014,39(1):40-45.
[9]吴中亮,任宁.天麻素注射液对大鼠脑缺血再灌注损伤细胞凋亡的影响[J].解放军医药学学报,2008,24(3):204-207.
[10]Sun L,Qiang R,Yang Y,et al.L-serine treatment may improve neurorestoration of rats after permanent focal cerebral ischemia potentially through improvement of neurorepair[J].PLoS One,2014,9(3):e 93405.
[11]Lee J K,Kim J E,Sivula M,et al.Nogo receptor antagonism promotes stroke recovery by enhancing axonal plasticity[J].J Neurosci,2004,24(27):6209-6217.
[12]蔡玉颖,刘志顺,王顺,等.电针曲池、足三里穴对脑缺血再灌注损伤大鼠神经功能缺损的影响[J].上海中医药大学学报,2009,23(6):64-66.
[13]王可博,庞国军,方智松.针刺合谷透后溪治疗中风偏瘫后手指拘挛127例[J].上海针灸杂志,2008,27(1):35.
[14]邬伟魁,张海燕,宋伟,等.以勿动蛋白-A及其受体为靶点的促神经再生中药研究[J].中国实验方剂学杂志,2012,18(1):239-242.
[15]Qin X D,Kang L Y,Liu Y,et al.Chinese medicine’s intervention effect on Nogo-A/NgR[J].Evid Based Complement Alternat Med,2012,2012:528482.
[16]王彤宇.天麻素注射液对急性脑梗死的神经保护作用[J].天津医药,2011,39(3):205-207.
[17]王德伟,刘黎青,周盛.针药结合对实验性脑缺血作用机制的研究进展[J].山东中医杂志,2009,28(12):881-882.
[18]魏彦珍,刘轲,张怀亮.针药结合治疗脑梗死机制研究进展[J].辽宁中医药大学学报,2014,16(2):217-219.
[19]崔晶晶,高俊虹,王玉敏,等.针药结合增效机制研究的新思路探讨[J].针刺研究,2010,35(2):146-149.
[20]刘炜,刘丽星,史晓伟,等.三七总皂苷对局灶性脑梗死大鼠海马CA 1区Nogo-A/NgR 1/RhoA信号通路蛋白表达的影响[J].中西医结合心脑血管病杂志,2014,12(11):1370-1373.