基于调控肠道菌群探讨中药防治脑卒中
|
摘要
肠道菌群是一个独特的生态系统,被称为人体"被遗忘的器官",被誉为人类的"第二基因组"。肠道菌群失调与许多中枢神经系统疾病相关,例如帕金森病、阿尔茨海默症、精神分裂症及多发性硬化等。脑卒中具有高的发病率、复发率、死亡率和致残率的特点。肠道菌群在脑卒中的发生、发展中起着关键的作用,可通过影响机体的吸收、代谢、血压、血糖、血脂及动脉粥样斑块等因素,进一步影响脑卒中的发病。中医认为脾胃气血流注失度、阴阳盛衰失衡,机体生理功能失调,化生"风、火、痰、虚、瘀"等病理产物,可致中风的发生。脾胃主腐熟运化水谷,肠道菌群影响饮食的消化吸收,现代研究的肠道菌群功能与中医之脾胃功能失调相关。因此,调整肠道菌群的稳态,可作为一个潜在的干预靶点预防和治疗缺血性脑卒中。中药干预脑卒中已经取得了很好的疗效,是否与调节肠道菌群有关,值得未来做进一步的研究。同时对中药有效成分(小檗碱、黄芩苷、白藜芦醇等),中药单方(丹参、红景天等)和中药组方(补阳还五汤、脑心通胶囊、补中益气汤等)防治脑缺血的研究进展进行综述,为缺血性脑卒中的预防和开发提供新的途径和思路。
The gut microbiome is a unique ecosystem,known as the " forgotten organ" of the human body,and the " second genome" of human. Gut microbiome imbalance is associated with many central nervous system diseases such as Parkinson's disease,Alzheimer's disease,schizophrenia and disseminated sclerosis. Stroke is characterized by high morbidity,recurrence,mortality,and disability. Gut microbiome plays a key role in the occurrence and development of stroke, which can further affect the onset of stroke by affecting the body's absorption,metabolism, blood pressure, blood sugar, blood lipids and atherosclerotic plaque. In Chinese medicine,it is believed that the spleen and stomach qi and blood flow loss,the Yin and yang imbalance,the body's physiological dysfunction, metaplasia " wind, fire, phlegm, deficiency, silt " and other pathological products,can cause the occurrence of stroke. The spleen and stomach are mainly involved for decomposing food,transporting and transforming nutrients from foodstuff,and the gut microbiome affect the digestion and absorption of the diet. The function of gut microbiome in modern research is related to the dysfunction of the spleen and stomach in Chinese medicine. Therefore,adjusting the homeostasis of the gut microbiome can be used as a potential intervention target to prevent and treat ischemic stroke. Traditional Chinese medicine(TCM) intervention has already achieved good results in stroke,and whether it is related to the regulation effect of gut microbiome is worthy of further research in the future. At the same time,the research progress of active ingredients in TCM(berberine,baicalin,resveratrol,et al),single TCM prescriptions(Salviae Miltiorrhizae Radix Et Rhizoma,Rhodiolae Crenulatae Radix Et Rhizoma,et al) and compound TCM prescriptions(Buyang Huanwu Tang,Naoxintong capsule,Buzhong Yiqi Tang) in prevention and treatment of cerebral ischemia were reviewed in this study,providing new ways and ideas for the prevention of ischemic stroke and development of new therapies.
The gut microbiome is a unique ecosystem,known as the " forgotten organ" of the human body,and the " second genome" of human. Gut microbiome imbalance is associated with many central nervous system diseases such as Parkinson's disease,Alzheimer's disease,schizophrenia and disseminated sclerosis. Stroke is characterized by high morbidity,recurrence,mortality,and disability. Gut microbiome plays a key role in the occurrence and development of stroke, which can further affect the onset of stroke by affecting the body's absorption,metabolism, blood pressure, blood sugar, blood lipids and atherosclerotic plaque. In Chinese medicine,it is believed that the spleen and stomach qi and blood flow loss,the Yin and yang imbalance,the body's physiological dysfunction, metaplasia " wind, fire, phlegm, deficiency, silt " and other pathological products,can cause the occurrence of stroke. The spleen and stomach are mainly involved for decomposing food,transporting and transforming nutrients from foodstuff,and the gut microbiome affect the digestion and absorption of the diet. The function of gut microbiome in modern research is related to the dysfunction of the spleen and stomach in Chinese medicine. Therefore,adjusting the homeostasis of the gut microbiome can be used as a potential intervention target to prevent and treat ischemic stroke. Traditional Chinese medicine(TCM) intervention has already achieved good results in stroke,and whether it is related to the regulation effect of gut microbiome is worthy of further research in the future. At the same time,the research progress of active ingredients in TCM(berberine,baicalin,resveratrol,et al),single TCM prescriptions(Salviae Miltiorrhizae Radix Et Rhizoma,Rhodiolae Crenulatae Radix Et Rhizoma,et al) and compound TCM prescriptions(Buyang Huanwu Tang,Naoxintong capsule,Buzhong Yiqi Tang) in prevention and treatment of cerebral ischemia were reviewed in this study,providing new ways and ideas for the prevention of ischemic stroke and development of new therapies.
引文
[1] Prabhakaran S,Ruff I,Bernstein R A. Acute stroke intervention:a systematic review[J]. J Am Med Asso,2015,313(14):1451-1462.
[2] GUO H,LI M J,LIU Q Q,et al. Danhong injection attenuates ischemia/reperfusion-induced brain damage which is associating with Nrf2 levels in vivo and in vitro[J]. Neurochem Res,2014,39(9):1817-1824.
[3] Kissela B M,Khoury J C,Alwell K,et al. Age at stroke:temporal trends in stroke incidence in a large,biracial population[J]. Neurology,2012,79(17):1781-1787.
[4]孟文婷,李东翔,佟玲.缺血性脑卒中的治疗研究进展[J].中国新药杂志,2016,25(10):1114-1120.
[5] Cani P D,Claude K. How gut microbes talk to organs:the role of endocrine and nervous routes[J]. Mol Metab,2016,5(9):743-752.
[6]游超,尹恝.缺血性卒中与肠道菌群研究进展[J].临床荟萃,2018,33(3):194-198.
[7] Yamashiro Y. Gut microbiota in health and disease[J].Ann Nutr Metab,2017,71(3/4):242-246.
[8] Singh V,Roth S,Llovera G,et al. Microbiota dysbiosis controls the neuroinflammatory response after stroke[J].J Neurosci,2016,36(28):7428-7440.
[9] Cerfbensussan N, Gaboriaurouthiau V. The immune system and the gut microbiota:friends or foes?[J]. Nat Rev Immunol,2010,10(10):735-744.
[10] ZHU X,YONG H,JING D,et al. Microbiota-gut-brain axis and the central nervous system[J]. Oncotarget,2017,8(32):53829-53838.
[11]袁亚辉,宋珏娴,黄礼媛,等.从脾胃浅论现代人脑中风的风险因素[J].中西医结合心脑血管病杂志,2011,9(7):877-877.
[12] Sender R,Fuchs S,Milo R. Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans[J]. Cell,2016,164(3):337-340.
[13]吴国琳,余国友,卢雯雯.中药复方对肠道微生态的调节作用研究现状[J].中国中药杂志,2015,40(18):3534-3537.
[14] Clemente J C,Manasson J,Scher J U. The role of the gut microbiome in systemic inflammatory disease[J].BMJ,2018,doi:10. 1136/bmj. j5145.
[15] Abdollahiroodsaz S,Abramson S B,Scher J U. The metabolic role of the gut microbiota in health and rheumatic disease:mechanisms and interventions[J].Nat Rev Rheumatol,2016,12(8):446-455.
[16] Tamburini S,SHEN N,WU H C,et al. The microbiome in early life:implications for health outcomes[J]. Nat Med,2016,22(7):713-722.
[17] Isaac S,Scher J U,Djukovic A,et al. Short-and longterm effects of oral vancomycin on the human intestinal microbiota[J]. J Antimicrob Chemother,2017,72(1):128-136.
[18] Aidy S E,Van d B B,Kleerebezem M. The small intestine microbiota, nutritional modulation and relevance for health[J]. Curr Opin Biotechnol,2015,doi:10. 1016/j. copbio. 2014. 09. 005.
[19]张美凤,金相任,潘如昕,等.肠道菌群对缺血性脑卒中影响的研究进展[J].医学综述,2017,23(18):3634-3637.
[20] YIN J,LIAO S,HE Y,et al. Dysbiosis of gut microbiota with reduced trimethylamine-N-oxide level in patients with large-artery atherosclerotic stroke or transient ischemic attack[J]. J Am Heart Assoc,2015,4(11):1-11.
[21] 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.
[22] Singh V,Roth S,Llovera G,et al. Microbiota dysbiosis controls the neuroinflammatory response after stroke[J].J Neurosci,2016,36(28):7428-7440.
[23] Yamashiro K,Tanaka R,Urabe T,et al. Gut dysbiosis is associated with metabolism and systemic inflammation in patients with ischemic stroke[J]. PLo S One,2017,12(2):e0171521.
[24]喻腾云,吴艳华,孙寒静,等.缺血性脑卒中中医病因病机的层次关系[J].吉林中医药,2016,36(4):328-331.
[25]孟湧生,杨振威,古楠,等.脾胃病变与中风病的关系探讨[J].中西医结合心脑血管病杂志,2016,14(14):1679-1681.
[26]顾玉宝,刘敬霞,王枫,等.人参皂苷治疗缺血性脑卒中研究进展[J].新中医,2017,49(4):194-197.
[27]刘艳艳,张凯,关家伟,等.人参皂苷对BALB/c小鼠肠道菌群的影响[J].现代生物医学进展,2015,15(6):1041-1045.
[28]刘抒雯,刘敬霞,虎喜成,等.三七总皂苷治疗缺血性脑卒中研究进展[J].中国实验方剂学杂志,2015,21(15):217-220.
[29]李雪晴,李丽,刘秀峰,等.三七皂苷的人肠道菌群体外代谢研究[J].药物生物技术,2017,24(3):218-223.
[30]唐岚,傅璐璐,沈丽婷,等.大鼠肠道菌群对三七总皂苷体外降解的研究[J].中草药,2018,49(2):396-399.
[31]李烨.知母皂苷(TSA)对实验性脑缺血再灌注损伤动物模型的保护作用研究[D].北京:北京中医药大学,2010.
[32]刘艳平,余自成,陈红君.基于肠道菌群代谢的知母皂苷BⅡ体外代谢转化研究[J].中国中医药信息杂志,2018,25(5):66-70.
[33]黄雄峰,汪建民.葛根素的神经保护作用机制研究进展[J].中国实验方剂学杂志,2015,21(4):224-230.
[34]王登远.葛根对肠道微生态、物质代谢和细胞因子表达的影响及其安全性的初步评价[D].南昌:南昌大学,2016.
[35]王文娟,任欢欢,韩吉春,等.黄芩苷抗脑缺血再灌注损伤的作用机制[J].中国实验方剂学杂志,2016,22(1):113-116.
[36]罗海燕,宋姗姗,黄暨生,等.黄芩苷对小鼠肠道菌群影响的量-时规律观察[J].中国医药指南,2010,8(32):42-43,49.
[37]崔祥,陶金华,江曙,等.小檗碱与肠道菌群的相互作用研究[J].中国微生态学杂志,2017,29(12):1373-1377.
[38] Shin J A,Lee H,Lim Y K,et al. Therapeutic effects of resveratrol during acute periods following experimental ischemic stroke[J]. J Neuroimmunol,2010,227(1/2):93-100.
[39]陈明亮.白藜芦醇通过重塑肠道菌群改善动脉粥样硬化的作用及机制研究[D].重庆:第三军医大学,2016.
[40]赵红霞,高滢.茶多酚对缺血-再灌注大鼠p38信号通路及细胞凋亡的影响[J].陕西医学杂志,2015,44(6):654-655,661.
[41]李桂花,曾本华,王玮,等.茶多酚对Apo E-/-小鼠肠道菌群多样性的影响[J].中国微生态学杂志,2012,24(8):673-676.
[42]张凯,关家伟,季煜,等.茶多酚的提取及其对抗生素所致肠道菌群失衡的调整和预防作用[J].天然产物研究与开发,2014,26(10):1654-1658,1704.
[43]李瑞奇.绿原酸对大、小鼠脑缺血再灌注模型的干预作用研究[D].郑州:河南中医学院,2014.
[44]瞿慧琴,张柏岳,段智璇,等.口服大黄与肠道菌群的相互影响[J].亚太传统医药,2017,13(13):39-40.
[45]葛建彬,卢红建,宋新建,等.枸杞多糖对小鼠脑缺血再灌注损伤的保护作用及其抑制NF-κB,TNF-α,IL-6和IL-1β表达的机制[J].中国中药杂志,2017,42(2):326-331.
[46]吴彩霞,王腾飞,余建强.枸杞多糖预处理对小鼠脑缺血-再灌注损伤的保护作用[J].中药材,2015,38(7):1454-1459.
[47]程翔.采用PCR-DGGE方法测定枸杞多糖对小鼠肠道菌群失调的调整作用[D].佳木斯:佳木斯大学,2013.
[48]张景秋,赵喜庆,吉训明,等.丹参抗脑缺血再灌注损伤的作用[J].河北医药,2010,32(24):3501-3503.
[49]曾桂梅,成金乐,彭丽华.丹参破壁饮片、常规饮片及传统粉末对小鼠肠道菌群的影响[J].今日药学,2015,25(2):103-106.
[50]陈娟,张珂,李国玉,等.蔷薇红景天对大鼠脑缺血的保护作用研究[J].石河子大学学报:自然科学版,2017,35(5):590-601.
[51]杨泽锐,曾桂梅,彭丽华,等.红景天破壁饮片对小鼠肠道菌群影响的初步研究[J].中国中药杂志,2015,40(15):3053-3058.
[52]孙明良,施玖龙.补阳还五汤与瑞代合用对缺血再灌注损伤大鼠保护作用及肠道菌群影响[J].中华中医药学刊,2015,33(9):2274-2278.
[53] XU H Y,SHI Y,ZHANG Y Q,et al. Identification of key active constituents of Buchang Naoxintong capsules with therapeutic effects against ischemic stroke by using an integrative pharmacology-based approach[J]. Mol Biosyst,2015,12(1):233-245.
[54]冯兴忠.补中益气汤促进肠道益生菌生长的实验研究[D].沈阳:辽宁中医药大学,2008.
[55]韩明亮.补中益气汤对脑缺血再灌注大鼠神经功能及梗死灶IL-1β和TNF-α表达的影响[J].河南中医,2017,37(7):1197-1200.
[56]王磊,朱迪娜,张文生.黄连解毒汤抗脑缺血作用研究进展[J].环球中医药,2012,5(3):234-237.
[57]罗海华,董姝,张晟,等.黄连解毒汤对小鼠肠道菌群的影响[J].热带医学杂志,2009,9(4):369-371.
[58]刘寒,张欢欢,侯建平,等.基于“脑肠相通”理论的脑缺血与肠道菌群的关系探讨[J].中药药理与临床,2017,33(6):173-176.
[2] GUO H,LI M J,LIU Q Q,et al. Danhong injection attenuates ischemia/reperfusion-induced brain damage which is associating with Nrf2 levels in vivo and in vitro[J]. Neurochem Res,2014,39(9):1817-1824.
[3] Kissela B M,Khoury J C,Alwell K,et al. Age at stroke:temporal trends in stroke incidence in a large,biracial population[J]. Neurology,2012,79(17):1781-1787.
[4]孟文婷,李东翔,佟玲.缺血性脑卒中的治疗研究进展[J].中国新药杂志,2016,25(10):1114-1120.
[5] Cani P D,Claude K. How gut microbes talk to organs:the role of endocrine and nervous routes[J]. Mol Metab,2016,5(9):743-752.
[6]游超,尹恝.缺血性卒中与肠道菌群研究进展[J].临床荟萃,2018,33(3):194-198.
[7] Yamashiro Y. Gut microbiota in health and disease[J].Ann Nutr Metab,2017,71(3/4):242-246.
[8] Singh V,Roth S,Llovera G,et al. Microbiota dysbiosis controls the neuroinflammatory response after stroke[J].J Neurosci,2016,36(28):7428-7440.
[9] Cerfbensussan N, Gaboriaurouthiau V. The immune system and the gut microbiota:friends or foes?[J]. Nat Rev Immunol,2010,10(10):735-744.
[10] ZHU X,YONG H,JING D,et al. Microbiota-gut-brain axis and the central nervous system[J]. Oncotarget,2017,8(32):53829-53838.
[11]袁亚辉,宋珏娴,黄礼媛,等.从脾胃浅论现代人脑中风的风险因素[J].中西医结合心脑血管病杂志,2011,9(7):877-877.
[12] Sender R,Fuchs S,Milo R. Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans[J]. Cell,2016,164(3):337-340.
[13]吴国琳,余国友,卢雯雯.中药复方对肠道微生态的调节作用研究现状[J].中国中药杂志,2015,40(18):3534-3537.
[14] Clemente J C,Manasson J,Scher J U. The role of the gut microbiome in systemic inflammatory disease[J].BMJ,2018,doi:10. 1136/bmj. j5145.
[15] Abdollahiroodsaz S,Abramson S B,Scher J U. The metabolic role of the gut microbiota in health and rheumatic disease:mechanisms and interventions[J].Nat Rev Rheumatol,2016,12(8):446-455.
[16] Tamburini S,SHEN N,WU H C,et al. The microbiome in early life:implications for health outcomes[J]. Nat Med,2016,22(7):713-722.
[17] Isaac S,Scher J U,Djukovic A,et al. Short-and longterm effects of oral vancomycin on the human intestinal microbiota[J]. J Antimicrob Chemother,2017,72(1):128-136.
[18] Aidy S E,Van d B B,Kleerebezem M. The small intestine microbiota, nutritional modulation and relevance for health[J]. Curr Opin Biotechnol,2015,doi:10. 1016/j. copbio. 2014. 09. 005.
[19]张美凤,金相任,潘如昕,等.肠道菌群对缺血性脑卒中影响的研究进展[J].医学综述,2017,23(18):3634-3637.
[20] YIN J,LIAO S,HE Y,et al. Dysbiosis of gut microbiota with reduced trimethylamine-N-oxide level in patients with large-artery atherosclerotic stroke or transient ischemic attack[J]. J Am Heart Assoc,2015,4(11):1-11.
[21] 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.
[22] Singh V,Roth S,Llovera G,et al. Microbiota dysbiosis controls the neuroinflammatory response after stroke[J].J Neurosci,2016,36(28):7428-7440.
[23] Yamashiro K,Tanaka R,Urabe T,et al. Gut dysbiosis is associated with metabolism and systemic inflammation in patients with ischemic stroke[J]. PLo S One,2017,12(2):e0171521.
[24]喻腾云,吴艳华,孙寒静,等.缺血性脑卒中中医病因病机的层次关系[J].吉林中医药,2016,36(4):328-331.
[25]孟湧生,杨振威,古楠,等.脾胃病变与中风病的关系探讨[J].中西医结合心脑血管病杂志,2016,14(14):1679-1681.
[26]顾玉宝,刘敬霞,王枫,等.人参皂苷治疗缺血性脑卒中研究进展[J].新中医,2017,49(4):194-197.
[27]刘艳艳,张凯,关家伟,等.人参皂苷对BALB/c小鼠肠道菌群的影响[J].现代生物医学进展,2015,15(6):1041-1045.
[28]刘抒雯,刘敬霞,虎喜成,等.三七总皂苷治疗缺血性脑卒中研究进展[J].中国实验方剂学杂志,2015,21(15):217-220.
[29]李雪晴,李丽,刘秀峰,等.三七皂苷的人肠道菌群体外代谢研究[J].药物生物技术,2017,24(3):218-223.
[30]唐岚,傅璐璐,沈丽婷,等.大鼠肠道菌群对三七总皂苷体外降解的研究[J].中草药,2018,49(2):396-399.
[31]李烨.知母皂苷(TSA)对实验性脑缺血再灌注损伤动物模型的保护作用研究[D].北京:北京中医药大学,2010.
[32]刘艳平,余自成,陈红君.基于肠道菌群代谢的知母皂苷BⅡ体外代谢转化研究[J].中国中医药信息杂志,2018,25(5):66-70.
[33]黄雄峰,汪建民.葛根素的神经保护作用机制研究进展[J].中国实验方剂学杂志,2015,21(4):224-230.
[34]王登远.葛根对肠道微生态、物质代谢和细胞因子表达的影响及其安全性的初步评价[D].南昌:南昌大学,2016.
[35]王文娟,任欢欢,韩吉春,等.黄芩苷抗脑缺血再灌注损伤的作用机制[J].中国实验方剂学杂志,2016,22(1):113-116.
[36]罗海燕,宋姗姗,黄暨生,等.黄芩苷对小鼠肠道菌群影响的量-时规律观察[J].中国医药指南,2010,8(32):42-43,49.
[37]崔祥,陶金华,江曙,等.小檗碱与肠道菌群的相互作用研究[J].中国微生态学杂志,2017,29(12):1373-1377.
[38] Shin J A,Lee H,Lim Y K,et al. Therapeutic effects of resveratrol during acute periods following experimental ischemic stroke[J]. J Neuroimmunol,2010,227(1/2):93-100.
[39]陈明亮.白藜芦醇通过重塑肠道菌群改善动脉粥样硬化的作用及机制研究[D].重庆:第三军医大学,2016.
[40]赵红霞,高滢.茶多酚对缺血-再灌注大鼠p38信号通路及细胞凋亡的影响[J].陕西医学杂志,2015,44(6):654-655,661.
[41]李桂花,曾本华,王玮,等.茶多酚对Apo E-/-小鼠肠道菌群多样性的影响[J].中国微生态学杂志,2012,24(8):673-676.
[42]张凯,关家伟,季煜,等.茶多酚的提取及其对抗生素所致肠道菌群失衡的调整和预防作用[J].天然产物研究与开发,2014,26(10):1654-1658,1704.
[43]李瑞奇.绿原酸对大、小鼠脑缺血再灌注模型的干预作用研究[D].郑州:河南中医学院,2014.
[44]瞿慧琴,张柏岳,段智璇,等.口服大黄与肠道菌群的相互影响[J].亚太传统医药,2017,13(13):39-40.
[45]葛建彬,卢红建,宋新建,等.枸杞多糖对小鼠脑缺血再灌注损伤的保护作用及其抑制NF-κB,TNF-α,IL-6和IL-1β表达的机制[J].中国中药杂志,2017,42(2):326-331.
[46]吴彩霞,王腾飞,余建强.枸杞多糖预处理对小鼠脑缺血-再灌注损伤的保护作用[J].中药材,2015,38(7):1454-1459.
[47]程翔.采用PCR-DGGE方法测定枸杞多糖对小鼠肠道菌群失调的调整作用[D].佳木斯:佳木斯大学,2013.
[48]张景秋,赵喜庆,吉训明,等.丹参抗脑缺血再灌注损伤的作用[J].河北医药,2010,32(24):3501-3503.
[49]曾桂梅,成金乐,彭丽华.丹参破壁饮片、常规饮片及传统粉末对小鼠肠道菌群的影响[J].今日药学,2015,25(2):103-106.
[50]陈娟,张珂,李国玉,等.蔷薇红景天对大鼠脑缺血的保护作用研究[J].石河子大学学报:自然科学版,2017,35(5):590-601.
[51]杨泽锐,曾桂梅,彭丽华,等.红景天破壁饮片对小鼠肠道菌群影响的初步研究[J].中国中药杂志,2015,40(15):3053-3058.
[52]孙明良,施玖龙.补阳还五汤与瑞代合用对缺血再灌注损伤大鼠保护作用及肠道菌群影响[J].中华中医药学刊,2015,33(9):2274-2278.
[53] XU H Y,SHI Y,ZHANG Y Q,et al. Identification of key active constituents of Buchang Naoxintong capsules with therapeutic effects against ischemic stroke by using an integrative pharmacology-based approach[J]. Mol Biosyst,2015,12(1):233-245.
[54]冯兴忠.补中益气汤促进肠道益生菌生长的实验研究[D].沈阳:辽宁中医药大学,2008.
[55]韩明亮.补中益气汤对脑缺血再灌注大鼠神经功能及梗死灶IL-1β和TNF-α表达的影响[J].河南中医,2017,37(7):1197-1200.
[56]王磊,朱迪娜,张文生.黄连解毒汤抗脑缺血作用研究进展[J].环球中医药,2012,5(3):234-237.
[57]罗海华,董姝,张晟,等.黄连解毒汤对小鼠肠道菌群的影响[J].热带医学杂志,2009,9(4):369-371.
[58]刘寒,张欢欢,侯建平,等.基于“脑肠相通”理论的脑缺血与肠道菌群的关系探讨[J].中药药理与临床,2017,33(6):173-176.