基于“肠道菌群-免疫反应”探讨针灸治疗缺血性脑卒中的作用机制
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摘要
当前,肠道菌群受到越来越多国内外学者们的关注,其与缺血性脑卒中(IS)的相关性研究也逐渐成为脑卒中领域的新兴热点。研究表明,肠道菌群可能是一类新的危险因子,其通过细菌代谢产物或免疫机制可直接或间接影响IS的发生发展。而针灸对于IS、肠道菌群及免疫炎性反应均有一定的正向调节作用。因此,本文围绕三者的相关性展开讨论,并基于"肠道菌群-免疫反应"探讨针灸在治疗IS中的应用,推测针灸或许可以通过纠正紊乱的肠道菌群,降低免疫炎性反应,进而促进卒中损伤后的脑组织及神经功能恢复。
At present,intestinal flora has attracted more and more attention from scholars in China and foreign countries,and its association with ischemic stroke(IS)has gradually become a new research hotspot in the field of stroke.Studies also showed that intestinal flora may be a risk factor which directly or indirectly affects the occurrence and development of IS through bacterial metabolites and immune activities.In the present paper,we review the positive effect of acupuncture and moxibustion in alleviating the symptoms of limb locomotor,speech,swallowing dysfunction,cognition,etc.to improve the IS patients' daily life ability and in strengthening the cellular immune function of the body.In addition,acupuncture and moxibustion have a positive effect in regulating intestinal flora and immune inflammation.Hence,in the present paper,we discuss their relationship and the possibility of application of acupuncture and moxibustion therapies to the treatment of IS according to the theory of"intestinal floraimmune response".It is thus reasonable to speculate that acupuncture and moxibustion can be used to promote the recovery of brain tissue injury and neurological function after stroke via correcting intestinal flora disturbance and reducing immune inflammatory response.In-depth exploration of the role of"intestinal flora-immune response"in the treatment of IS and the specific regulatory function of acupuncture and moxibustion will provide new ideas and research approaches to reveal their mechanisms in the treatment of stroke from a new perspective.
At present,intestinal flora has attracted more and more attention from scholars in China and foreign countries,and its association with ischemic stroke(IS)has gradually become a new research hotspot in the field of stroke.Studies also showed that intestinal flora may be a risk factor which directly or indirectly affects the occurrence and development of IS through bacterial metabolites and immune activities.In the present paper,we review the positive effect of acupuncture and moxibustion in alleviating the symptoms of limb locomotor,speech,swallowing dysfunction,cognition,etc.to improve the IS patients' daily life ability and in strengthening the cellular immune function of the body.In addition,acupuncture and moxibustion have a positive effect in regulating intestinal flora and immune inflammation.Hence,in the present paper,we discuss their relationship and the possibility of application of acupuncture and moxibustion therapies to the treatment of IS according to the theory of"intestinal floraimmune response".It is thus reasonable to speculate that acupuncture and moxibustion can be used to promote the recovery of brain tissue injury and neurological function after stroke via correcting intestinal flora disturbance and reducing immune inflammatory response.In-depth exploration of the role of"intestinal flora-immune response"in the treatment of IS and the specific regulatory function of acupuncture and moxibustion will provide new ideas and research approaches to reveal their mechanisms in the treatment of stroke from a new perspective.
引文
[1]BENAKIS C,BREA D,CABALLERO S,et al.Commensal microbiota affects ischemic stroke outcome by regulating intestinalγδT cells[J].Nat Med,2016,22(5):516-523.
[2]金竹青,周鑫,杜梧榕,等.MCPIP1蛋白介导电针治疗急性缺血性脑卒中血脑屏障损害作用的研究[J].浙江中医药大学学报,2016,40(12),870-875.
[3]WANG H X,WANG Y P.Gut microbiota-brain axis[J].Chin Med J,2016,129(19):2373-2380.
[4]ZHU W F,GREGORY J C,ORG E,et al.Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk[J].Cell,2016,165(1):111-124.
[5]FU J Y,BONDER M J,CENIT M C,et al.The gut microbiome contributes to a substantial proportion of the variation in blood lipids[J].Circ Res,2015,117(9):817-824.
[6]金华,金钊,张蕾蕾,等.肠道菌群可能为高血压发病的环境因素[J].中国微生态学杂志,2015,27(1):121-124.
[7]江美玲,许岸高.2型糖尿病患者肠道菌群特征分析[J].广东医学,2013,34(13):2006-2010.
[8]SWIDSINSKI A,LOENING-BAUCKE V,KRGER M,et al.Central nervous system and the colonic bioreactor:analysis of colonic microbiota in patients with stroke unravels unknown mechanisms of the host Defense after brain injury[J].Intest Res,2012,10(4):332.
[9]YAMASHIRO K,TANAKA R,URABE T,et al.Gut dysbiosis is associated with metabolism and systemic inflammation in patients with ischemic stroke[J].PLoS One,2017,12(2):e0171521.
[10]朱尧,费世早,庞洪波,等.调节性T细胞与缺血性脑损伤的研究进展[J].医学综述,2017,23(9):1702-1706.
[11]陈瑞清,谭盛,陈健,等.大鼠急性脑缺血后CD4+CD25+调节性T细胞、Foxp3表达及其意义[J].南方医科大学学报,2012,32(5):659-663.
[12]陈晓菲,许文华,任明山.急性脑梗死患者外周血CD4+CD25+CD127low调节性T细胞表达及其临床意义[J].安徽医科大学学报,2014,49(5):633-636.
[13]DOLATI S,AHMADI M,KHALILI M,et al.Peripheral Th17/Treg imbalance in elderly patients with ischemic stroke[J].Neurol Sci,2018,39(4):647-654.
[14]于泳,郑鹏远.肠道细菌、肠黏膜屏障与肠功能障碍[J].胃肠病学和肝病学杂志,2013,22(2):121-122.
[15]PONFERRADAá,CASO J R,ALOU L,et al.The role of PPARγon restoration of colonic homeostasis after experimental stress-induced inflammation and dysfunction[J].Gastroenterology,2007,132(5):1791-1803.
[16]CASO J R,HURTADO O,PEREIRA M P,et al.Colonic bacterial translocation as a possible factor in stress-worsening experimental stroke outcome[J].Am J Physiol Regul Integr Comp Physiol,2009,296(4):R979-R985.
[17]许杰,王伊龙,王拥军.肠道菌群与缺血性卒中[J].中国卒中杂志,2017,12(2):179-182.
[18]IADECOLA C,ANRATHER J.The immunology of stroke:from mechanisms to translation[J].Nat Med,2011,17(7):796-808.
[19]PRINZ I,SILVA-SANTOS B,PENNINGTON D J.Functional development ofγδT cells[J].Eur J Immunol,2013,43(8):1988-1994.
[20]王文建,郑跃杰.肠道菌群与中枢神经系统相互作用及相关疾病[J].中国微生态学杂志,2016,28(2):240-245.
[21]LIESZ A,SURI-PAYER E,VELTKAMP C,et al.Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke[J].Nat Med,2009,15(2):192-199.
[22]宁玉楼,成泽东.从气机升降理论探讨针灸与肠道菌群的关系[J].中医杂志,2017,58(1):31-33.
[23]李艳,宋亚刚,白明,等.基于调控肠道菌群探讨中药防治脑卒中[J].中国实验方剂学杂志,2019,25(1):228-234.
[24]郑婉群,曹奕.针刺抗缺血性脑卒中细胞凋亡的研究进展[J].浙江中医药大学学报,2013,37(5):653-655.
[25]彭劲,彭文达,朱茂,等.针灸预防脑卒中后抑郁症的疗效观察[J].中医药导报,2016,22(24):58-59.
[26]CHEN L F,FANG J Q,MA R J,et al.Additional effects of acupuncture on early comprehensive rehabilitation in patients with mild to moderate acute ischemic stroke:a multicenter randomized controlled trial[J].BMC Complement Altern Med,2016,16(1):226.
[27]刘月秋,刘辉.针灸对脑卒中患者细胞免疫功能的影响[J].光明中医,2016,31(13):1854-1855.
[28]LAN L,TAO J,CHEN A,et al.Electroacupuncture exerts anti-inflammatory effects in cerebral ischemia-reperfusion injured rats via suppression of the TLR4/NF-КB pathway[J].Int J Mol Med,2013,31(1):75-80.
[29]罗文舒,吴永刚,杨卓欣,等.针刺督脉对局灶性脑缺血大鼠脑组织TNF-αmRNA表达的影响[J].中国中医急症,2012,21(4):572-573.
[30]倪光夏,石学敏,王占奎,等.醒脑开窍针刺法对缺血再灌注大鼠大脑皮层IL-1RI和TNFR-I的mRNA表达的影响[J].南京中医药大学学报,2012,28(6):538-540.
[31]JIN Y L,ZHAO Q,ZHOU K H,et al.Acupuncture for functional dyspepsia:a single blinded,randomized,controlled trial[J].Evid Based Complement Alternat Med,2015,2015:904-926.
[32]罗容,章薇.消化系统疾病谱中针灸优势病种的研究近况[J].中国中医急症,2012,21(8):1287-1289.
[33]孙路强,张微,魏韬,等.针灸对肠道菌群影响的研究进展[J].湖南中医杂志,2018,34(1):190-193.
[34]王树东,成泽东,金迪,等.温和灸腹部募穴对实验性大鼠肠道菌群失调的影响[J].上海针灸杂志,2010,29(8):546-548.
[35]侯天舒,韩晓霞,杨阳,等.电针对溃疡性结肠炎大鼠肠道微生态的保护作用[J].针刺研究,2014,39(1):27-34.
[36]余英.微生态制剂配合针灸治疗老年慢传输型便秘的临床观察[J].实用老年医学,2007,21(5):353-354.
[37]XU Z T,LI R F,ZHU C L,et al.Effect of acupuncture treatment for weight loss on gut flora in patients with simple obesity[J].Acupunct Med,2013,31(1):116-117.
[38]WANG X M,LU Y,WU L Y,et al.Moxibustion inhibits interleukin-12and tumor necrosis factor alpha and modulates intestinal flora in rat with ulcerative colitis[J].World J Gastroenterol,2012,18(46):6819-6828.
[39]张博,熊壮,姜鑫.自拟扶正平溃汤联合针灸治疗慢性溃疡性结肠炎的疗效及对肠道菌群失调和Th17/Treg细胞免疫平衡的影响[J].现代中西医结合杂志,2018,27(11):1164-1167.
[2]金竹青,周鑫,杜梧榕,等.MCPIP1蛋白介导电针治疗急性缺血性脑卒中血脑屏障损害作用的研究[J].浙江中医药大学学报,2016,40(12),870-875.
[3]WANG H X,WANG Y P.Gut microbiota-brain axis[J].Chin Med J,2016,129(19):2373-2380.
[4]ZHU W F,GREGORY J C,ORG E,et al.Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk[J].Cell,2016,165(1):111-124.
[5]FU J Y,BONDER M J,CENIT M C,et al.The gut microbiome contributes to a substantial proportion of the variation in blood lipids[J].Circ Res,2015,117(9):817-824.
[6]金华,金钊,张蕾蕾,等.肠道菌群可能为高血压发病的环境因素[J].中国微生态学杂志,2015,27(1):121-124.
[7]江美玲,许岸高.2型糖尿病患者肠道菌群特征分析[J].广东医学,2013,34(13):2006-2010.
[8]SWIDSINSKI A,LOENING-BAUCKE V,KRGER M,et al.Central nervous system and the colonic bioreactor:analysis of colonic microbiota in patients with stroke unravels unknown mechanisms of the host Defense after brain injury[J].Intest Res,2012,10(4):332.
[9]YAMASHIRO K,TANAKA R,URABE T,et al.Gut dysbiosis is associated with metabolism and systemic inflammation in patients with ischemic stroke[J].PLoS One,2017,12(2):e0171521.
[10]朱尧,费世早,庞洪波,等.调节性T细胞与缺血性脑损伤的研究进展[J].医学综述,2017,23(9):1702-1706.
[11]陈瑞清,谭盛,陈健,等.大鼠急性脑缺血后CD4+CD25+调节性T细胞、Foxp3表达及其意义[J].南方医科大学学报,2012,32(5):659-663.
[12]陈晓菲,许文华,任明山.急性脑梗死患者外周血CD4+CD25+CD127low调节性T细胞表达及其临床意义[J].安徽医科大学学报,2014,49(5):633-636.
[13]DOLATI S,AHMADI M,KHALILI M,et al.Peripheral Th17/Treg imbalance in elderly patients with ischemic stroke[J].Neurol Sci,2018,39(4):647-654.
[14]于泳,郑鹏远.肠道细菌、肠黏膜屏障与肠功能障碍[J].胃肠病学和肝病学杂志,2013,22(2):121-122.
[15]PONFERRADAá,CASO J R,ALOU L,et al.The role of PPARγon restoration of colonic homeostasis after experimental stress-induced inflammation and dysfunction[J].Gastroenterology,2007,132(5):1791-1803.
[16]CASO J R,HURTADO O,PEREIRA M P,et al.Colonic bacterial translocation as a possible factor in stress-worsening experimental stroke outcome[J].Am J Physiol Regul Integr Comp Physiol,2009,296(4):R979-R985.
[17]许杰,王伊龙,王拥军.肠道菌群与缺血性卒中[J].中国卒中杂志,2017,12(2):179-182.
[18]IADECOLA C,ANRATHER J.The immunology of stroke:from mechanisms to translation[J].Nat Med,2011,17(7):796-808.
[19]PRINZ I,SILVA-SANTOS B,PENNINGTON D J.Functional development ofγδT cells[J].Eur J Immunol,2013,43(8):1988-1994.
[20]王文建,郑跃杰.肠道菌群与中枢神经系统相互作用及相关疾病[J].中国微生态学杂志,2016,28(2):240-245.
[21]LIESZ A,SURI-PAYER E,VELTKAMP C,et al.Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke[J].Nat Med,2009,15(2):192-199.
[22]宁玉楼,成泽东.从气机升降理论探讨针灸与肠道菌群的关系[J].中医杂志,2017,58(1):31-33.
[23]李艳,宋亚刚,白明,等.基于调控肠道菌群探讨中药防治脑卒中[J].中国实验方剂学杂志,2019,25(1):228-234.
[24]郑婉群,曹奕.针刺抗缺血性脑卒中细胞凋亡的研究进展[J].浙江中医药大学学报,2013,37(5):653-655.
[25]彭劲,彭文达,朱茂,等.针灸预防脑卒中后抑郁症的疗效观察[J].中医药导报,2016,22(24):58-59.
[26]CHEN L F,FANG J Q,MA R J,et al.Additional effects of acupuncture on early comprehensive rehabilitation in patients with mild to moderate acute ischemic stroke:a multicenter randomized controlled trial[J].BMC Complement Altern Med,2016,16(1):226.
[27]刘月秋,刘辉.针灸对脑卒中患者细胞免疫功能的影响[J].光明中医,2016,31(13):1854-1855.
[28]LAN L,TAO J,CHEN A,et al.Electroacupuncture exerts anti-inflammatory effects in cerebral ischemia-reperfusion injured rats via suppression of the TLR4/NF-КB pathway[J].Int J Mol Med,2013,31(1):75-80.
[29]罗文舒,吴永刚,杨卓欣,等.针刺督脉对局灶性脑缺血大鼠脑组织TNF-αmRNA表达的影响[J].中国中医急症,2012,21(4):572-573.
[30]倪光夏,石学敏,王占奎,等.醒脑开窍针刺法对缺血再灌注大鼠大脑皮层IL-1RI和TNFR-I的mRNA表达的影响[J].南京中医药大学学报,2012,28(6):538-540.
[31]JIN Y L,ZHAO Q,ZHOU K H,et al.Acupuncture for functional dyspepsia:a single blinded,randomized,controlled trial[J].Evid Based Complement Alternat Med,2015,2015:904-926.
[32]罗容,章薇.消化系统疾病谱中针灸优势病种的研究近况[J].中国中医急症,2012,21(8):1287-1289.
[33]孙路强,张微,魏韬,等.针灸对肠道菌群影响的研究进展[J].湖南中医杂志,2018,34(1):190-193.
[34]王树东,成泽东,金迪,等.温和灸腹部募穴对实验性大鼠肠道菌群失调的影响[J].上海针灸杂志,2010,29(8):546-548.
[35]侯天舒,韩晓霞,杨阳,等.电针对溃疡性结肠炎大鼠肠道微生态的保护作用[J].针刺研究,2014,39(1):27-34.
[36]余英.微生态制剂配合针灸治疗老年慢传输型便秘的临床观察[J].实用老年医学,2007,21(5):353-354.
[37]XU Z T,LI R F,ZHU C L,et al.Effect of acupuncture treatment for weight loss on gut flora in patients with simple obesity[J].Acupunct Med,2013,31(1):116-117.
[38]WANG X M,LU Y,WU L Y,et al.Moxibustion inhibits interleukin-12and tumor necrosis factor alpha and modulates intestinal flora in rat with ulcerative colitis[J].World J Gastroenterol,2012,18(46):6819-6828.
[39]张博,熊壮,姜鑫.自拟扶正平溃汤联合针灸治疗慢性溃疡性结肠炎的疗效及对肠道菌群失调和Th17/Treg细胞免疫平衡的影响[J].现代中西医结合杂志,2018,27(11):1164-1167.