中医药联合干细胞抗肝纤维化的思路与进展
|
摘要
目的:从中医视角解读干细胞,探讨与干细胞相关的中医基础理论,总结近年来中医药联合干细胞抗肝纤维化的思路与进展,试图为中医理论现代化研究提供一个新的结合点,为中药联合干细胞治疗提供理论依据。检索策略:以中医、中药、干细胞、肝纤维化、肝硬化、traditional chinese medicine、stem cell、liver fibrosis、hepatic fibrosis、hepatic cirrhosis、liver cirrhosis为主题词,检索并筛选了Pubmed、中国知网、维普数据库、万方数据库近10年的中英文文献,就对中医药联合干细胞疗法的研究综述。结果:肝纤维化发病率高,目前仍无逆转肝纤维化的理想方法。干细胞是一类具有自我更新、增殖、分化能力的多潜能功能细胞,在组织工程、治疗组织坏死性疾病以及作为基因治疗的载体等方面有巨大的应用价值。设法诱导干细胞使之定向分化成为所需的成熟功能细胞,是目前干细胞移植疗法最关键的环节。从中医基础理论角度看,中医学说中的"精"与干细胞有较大的相关性,从功能上一脉同源,这为二者的结合奠定了基础,且中医药不仅可以通过"益髓填精"从而促进干细胞的生成,而且通过"养肝阴补气血"改善肝脏内环境,使内环境更利于干细胞的定向分化,进而对肝脏进行修复,以达到抗肝纤维化的最终结果。结论:干细胞与先天之精密切相关,利用中医药的优势及多靶点作用的特性促进干细胞增殖分化最终达到抗肝纤维化的治疗目的方法可行性大。
Objective:To explain the basic theory of TCM, explore the thought and progress of TCM combined with stem cells to anti-hepatic fibrosis to provide a new modernization of TCM theory and theoretical basis for the treatment of TCM combined with stem cells. Method: Taking TCM, Chinese medicine, stem cells, traditional Chinese medicine,stem cell,liver fibrosis,hepatic fibrosis and liver cirrhosis as the keywords,we retrieved the literature for nearly five years in Pubmed, CNKI and WANFANG DATA,making a review of research on treatment of TCM combined with stem cells. Result: The incidence of hepatic fibrosis is high,which has no optimal method. Stem cells are a class of pluripotent cells that have self-renewal and proliferative capacity,which have great application value in tissue engineering, treatment of necrotic disease and carrier of gene therapy. Inducing stem cells committed differentiation then making it mature functional cells we needed is the key link of stem cell transplantation. From the perspective of TCM theory, the "essence" in TCM theory has a great correlation with stem cells. There is a homologous in function,which lays the groundwork for the combination of the two. Furthermore,traditional Chinese medicine can not only promote the generation of stem cells by "enriching kidney essence", but also improve the environment of liver through "nourishing the liver and supplementing Qi and blood" to make the internal environment more conducive to stem cells committed differentiation so as to achieve the ultimate results of anti-liver fibrosis. Conclusion: Stem cells are closely related to essence and using the advantages of TCM and the characteristics of multiple targets to promote the committed differentiation of stem cells to achieve the therapeutic aim of anti-liver fibrosis is feasible.
Objective:To explain the basic theory of TCM, explore the thought and progress of TCM combined with stem cells to anti-hepatic fibrosis to provide a new modernization of TCM theory and theoretical basis for the treatment of TCM combined with stem cells. Method: Taking TCM, Chinese medicine, stem cells, traditional Chinese medicine,stem cell,liver fibrosis,hepatic fibrosis and liver cirrhosis as the keywords,we retrieved the literature for nearly five years in Pubmed, CNKI and WANFANG DATA,making a review of research on treatment of TCM combined with stem cells. Result: The incidence of hepatic fibrosis is high,which has no optimal method. Stem cells are a class of pluripotent cells that have self-renewal and proliferative capacity,which have great application value in tissue engineering, treatment of necrotic disease and carrier of gene therapy. Inducing stem cells committed differentiation then making it mature functional cells we needed is the key link of stem cell transplantation. From the perspective of TCM theory, the "essence" in TCM theory has a great correlation with stem cells. There is a homologous in function,which lays the groundwork for the combination of the two. Furthermore,traditional Chinese medicine can not only promote the generation of stem cells by "enriching kidney essence", but also improve the environment of liver through "nourishing the liver and supplementing Qi and blood" to make the internal environment more conducive to stem cells committed differentiation so as to achieve the ultimate results of anti-liver fibrosis. Conclusion: Stem cells are closely related to essence and using the advantages of TCM and the characteristics of multiple targets to promote the committed differentiation of stem cells to achieve the therapeutic aim of anti-liver fibrosis is feasible.
引文
[1] 张莎莎,吕文良,张旭.窗体底端肝窦内皮细胞与肝纤维化形成的研究概况 [J].中华中医药学刊,2012,30(7):1508-1510.
[2] 崔富强.中国人群乙型病毒性肝炎血清流行病学调查——乙型肝炎疫苗接种降低乙型肝炎病毒感染率[J].中国疫苗和免疫,2010,16(4):341-353.
[3] 邓秋云,钟革,韦敬航,等.2014年广西1-29岁人群乙型肝炎血清流行病学调查及乙型肝炎疫苗接种情况分析[J].中国疫苗和免疫,2017,23(4):406-410.
[4] 戴志澄,祁国明.中国病毒性肝炎:血清流行病调查(上卷)[M].北京:科学技术文献出版社,1997:60-71.
[5] Friedman SL.Molecular mechanisms of hepatic fibrosis and principles of therapy[J].J Gastroenterol, 1997,32(3):424-430.
[6] Wang YJ,Sun ZQ,Quan QZ,et al.Fat-storing cells liver fibrosis[J].China Natl New Gastroenterol,1996,2:58-60.
[7] 张孝盈,宓余强.肝纤维化影响因素的研究进展[J].医学综述,2018,24(6):1062-1066.
[8] 李军,陈攀,陈孝,等.以DJ-1蛋白为靶点治疗肝纤维化的研究进展[J].中国药理学通报,2018,34(3):309-312.
[9] 白文元,姚希贤,冯丽英,等.肝纤维化的研究现状[J].世界华人消化杂志,2000,8(11):1267-1268.
[10] Jackson KA,Majka SM,Wang H,et al.Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells[J].J Clin Invest,2001,107(11):1395.
[11] Ciulla MM,Lazzari L,Pacchiana R,et al.Homing of peripherally injected bone marrow cells in rat after experimental myocardial injury[J].Haematologica,2003,88(6):614.
[12] 李豫皖,朱喜忠,金瑛,等. 体外定向诱导人羊膜间充质干细胞向骨、软骨及脂肪细胞的分化[J]. 中国组织工程研究,2017(1):122-127.
[13] 王政,林凯. 大鼠骨髓胚胎样干细胞生物学特性和分化潜能[J]. 中国组织工程研究,2017(1):43-48.
[14] 郭宪立,刘跃,周丽敏,等. 脐血干细胞移植修复失代偿期肝硬化[J].中国组织工程研究,2016,20(14):2080-2085.
[15] 张岁,郭力红,杨大伟,等. 脐血干细胞移植治疗慢性肝衰竭患者的临床观察[J]. 实用医学杂志,2017(4):565-568.
[16] 王亚莉. 自体骨髓间充质干细胞转化神经干细胞移植治疗脑瘫30例[D].杭州:浙江大学,2017.
[17] 王振常,黄贵华,黄晶晶,等.纯化自体骨髓干细胞经肝动脉移植的疗效及安全性分析失代偿期肝硬化[J].胃肠病学与肝病学杂志, 2014,23: 497-500.
[18] 彭蕾,汤磊,叶珺,等. 自体骨髓间充质干细胞移植治疗失代偿期肝硬化的疗效[J]. 中国肝脏病杂志(电子版),2017,9(1):83-86.
[19] El-Ansary M,Abdel-Aziz I,Mogawer S,et al.Phase II trial:undifferentiated versus differentiated autologous mesenchymal stem cells transplantation in Egyptian patients with HCV induced liver cirrhosis[J].Stem Cell Rev,2012,8(3):972-981.
[20] Kharaziha P,Hellstrom PM,Noorinayer B,et al.Improvement of liver function in liver cirrhosis patients after autologous mesenchymal stem cell injection:a phase I-II clinical trial[J].Eur J Gastroenterol Hepatol,2009,21(10):1199-1205.
[21] 徐喨,施启鹏,周晗,等. 间充质干细胞旁分泌物质诱导肝星状细胞凋亡的体外研究[J]. 南京医科大学学报(自然科学版),2014,34(8):1040-1045.
[22] Khubutiya MS,Vagabov AV,Temnov AA,et al.Paracrine mechanisms of proliferative,anti-apoptotic and anti-in flammatory effects of mesenchymal stromal cells in models of acute organ injury[J]. Cytotherapy,2014,16(5):579-585.
[23] Yuan S,Jiang T,Sun L,et al.The role of bone marrow mesenchymal stem cells in the treatment of acute liver failure[J]. Biomed Res Int, 2013, 2013: 251846.
[24] Bao X,Wei J,Feng M,et al.Transplantation of human bone marrow-derived mesenchymal stem cells promotes behavioral recovery and endogenous neurogenesis after cerebral ischemia in rats[J].Br Res,2011,1367(1): 103-113.
[25] Li J,Zhu H,Liu Y,et al. Human mesenchymal stem cell transplantation protects against cerebral ischemic injury and upregulates interleukin-10 expression in Macacafascicularis[J].Br Res,2010,1334(1):65-72.
[26] 具星爱,刘滋康,郭子宽,等.肝细胞生长因子基因修饰骨髓间充质干细胞[J].中外医疗,2012,31(4):29,117.
[27] 孙广仁. 中医基础理论[M]. 北京:中国中医药出版社, 2007: 66-68.
[28] 黄帝内经.[M].7版.北京:人民卫生出版社,2013.
[29] 张金生,张宝霞.“肾精”与“干细胞”的同一性认识[J].中华中医药学刊,2018,36(2):326-328.
[30] 徐德成,马迎民,范吉平.中医“肾精”的现代医学内涵[J].中医杂志,2017,58(22):1891-1897.
[31] 孙丽芳,张丽欣,王志刚,等.干细胞治疗肝硬化的中医理论分析[J].临床合理用药杂志,2013,6(31):67-78.
[32] Wakitani S,SaitoT,Caplan AI.Myogenic cells derived from rat bone marrow mesenchymal stem cels exposed to 5-azacytidine[J].Muscle Nerve,1995,18(12):1417-1426.
[33] Reyes M,Lund T,Lenvik T,et al.Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells[J].Blood,2001,98:2615-2625.
[34] Mark F Pittenger,Alastair M Macay,Stephen C Bec,et al.Multili-neagepotential of adult human mesenchymal stem cells[J].Science,1999,284(5411):143-147.
[35] J Sanchenz-Ramos S,Song F,Cardozo Pelaez C,et al.Adult bone marrows tromal cells different iate into neural cells invi tro[J].ExpNeurol,2000,164(2):247-256.
[36] Jiang Y,Jahagirdar BN,Reinhardt RL,et al.Pluripotency of mesenchymal stem cells derive from adut marrow[J].Nature,2012,418(6893):41-49.
[37] 许静,张晶晶,郭非非,等. 淫羊藿黄酮类主要成分促进骨髓间充质干细胞向成骨细胞增殖分化作用及机制的影响[J]. 中国实验方剂学杂志,2017(14):113-120.
[38] 汪宏锦,李晶晶,柯慧,等.中药对神经干细胞增殖分化信号通路的综合调控作用分析[J].中国中药杂志,2017,42(21):4093-4103.
[39] 王玉莹,梁喜才,王雅萌,等.蛇床子素上调miR-9促进神经干细胞分化的研究[J].中药药理与临床,2018,34(1):44-48.
[40] 郜峦,王键,程发峰,等.益气活血化痰中药复方对大鼠胚胎神经干细胞生长分化增殖的影响机制研究[J].北京中医药大学学报,2016,39(2):113-118.
[41] Zhu XK, Zhu BD,Liu J,et al.Study on SCF production of bone marrow stromal cell stimulated with astragalus mere-branaceus in anemic mice[J].Pharmacol Clin Chin Mater Med(中药药理与临床),2001,17(5):19-20.
[42] Liu Ch,Liu P,Hu YY,et al.Progress of clinical and basic research on liver fibrosis with traditional Chinese medicine[J].Wold Sci Technol-Modern Tradit Chin Med,2007,9(2):112-118.
[43] 那坤.柔肝颗粒对肝纤维化大鼠TGFβ1/Smads信号转导通路的影响[D].哈尔滨:黑龙江中医药大学,2010.
[44] 赵永忠,韦铮武,漆志平,等.荔枝核总黄酮对肝纤维化大鼠肿瘤坏死因子相关凋亡诱导配体表达的影响[J].中国中西医结合消化杂志,2010,18(4):223-226.
[45] 徐列明.中医药抗肝纤维化疗效评价的探索[J].临床肝胆病杂志,2017,33(5):825-828.
[46] 李伟建,杨秋蕊,王振宇,等.生物人工肝的研究现状与进展[J].肝脏,2018,23(1):80-83.
[2] 崔富强.中国人群乙型病毒性肝炎血清流行病学调查——乙型肝炎疫苗接种降低乙型肝炎病毒感染率[J].中国疫苗和免疫,2010,16(4):341-353.
[3] 邓秋云,钟革,韦敬航,等.2014年广西1-29岁人群乙型肝炎血清流行病学调查及乙型肝炎疫苗接种情况分析[J].中国疫苗和免疫,2017,23(4):406-410.
[4] 戴志澄,祁国明.中国病毒性肝炎:血清流行病调查(上卷)[M].北京:科学技术文献出版社,1997:60-71.
[5] Friedman SL.Molecular mechanisms of hepatic fibrosis and principles of therapy[J].J Gastroenterol, 1997,32(3):424-430.
[6] Wang YJ,Sun ZQ,Quan QZ,et al.Fat-storing cells liver fibrosis[J].China Natl New Gastroenterol,1996,2:58-60.
[7] 张孝盈,宓余强.肝纤维化影响因素的研究进展[J].医学综述,2018,24(6):1062-1066.
[8] 李军,陈攀,陈孝,等.以DJ-1蛋白为靶点治疗肝纤维化的研究进展[J].中国药理学通报,2018,34(3):309-312.
[9] 白文元,姚希贤,冯丽英,等.肝纤维化的研究现状[J].世界华人消化杂志,2000,8(11):1267-1268.
[10] Jackson KA,Majka SM,Wang H,et al.Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells[J].J Clin Invest,2001,107(11):1395.
[11] Ciulla MM,Lazzari L,Pacchiana R,et al.Homing of peripherally injected bone marrow cells in rat after experimental myocardial injury[J].Haematologica,2003,88(6):614.
[12] 李豫皖,朱喜忠,金瑛,等. 体外定向诱导人羊膜间充质干细胞向骨、软骨及脂肪细胞的分化[J]. 中国组织工程研究,2017(1):122-127.
[13] 王政,林凯. 大鼠骨髓胚胎样干细胞生物学特性和分化潜能[J]. 中国组织工程研究,2017(1):43-48.
[14] 郭宪立,刘跃,周丽敏,等. 脐血干细胞移植修复失代偿期肝硬化[J].中国组织工程研究,2016,20(14):2080-2085.
[15] 张岁,郭力红,杨大伟,等. 脐血干细胞移植治疗慢性肝衰竭患者的临床观察[J]. 实用医学杂志,2017(4):565-568.
[16] 王亚莉. 自体骨髓间充质干细胞转化神经干细胞移植治疗脑瘫30例[D].杭州:浙江大学,2017.
[17] 王振常,黄贵华,黄晶晶,等.纯化自体骨髓干细胞经肝动脉移植的疗效及安全性分析失代偿期肝硬化[J].胃肠病学与肝病学杂志, 2014,23: 497-500.
[18] 彭蕾,汤磊,叶珺,等. 自体骨髓间充质干细胞移植治疗失代偿期肝硬化的疗效[J]. 中国肝脏病杂志(电子版),2017,9(1):83-86.
[19] El-Ansary M,Abdel-Aziz I,Mogawer S,et al.Phase II trial:undifferentiated versus differentiated autologous mesenchymal stem cells transplantation in Egyptian patients with HCV induced liver cirrhosis[J].Stem Cell Rev,2012,8(3):972-981.
[20] Kharaziha P,Hellstrom PM,Noorinayer B,et al.Improvement of liver function in liver cirrhosis patients after autologous mesenchymal stem cell injection:a phase I-II clinical trial[J].Eur J Gastroenterol Hepatol,2009,21(10):1199-1205.
[21] 徐喨,施启鹏,周晗,等. 间充质干细胞旁分泌物质诱导肝星状细胞凋亡的体外研究[J]. 南京医科大学学报(自然科学版),2014,34(8):1040-1045.
[22] Khubutiya MS,Vagabov AV,Temnov AA,et al.Paracrine mechanisms of proliferative,anti-apoptotic and anti-in flammatory effects of mesenchymal stromal cells in models of acute organ injury[J]. Cytotherapy,2014,16(5):579-585.
[23] Yuan S,Jiang T,Sun L,et al.The role of bone marrow mesenchymal stem cells in the treatment of acute liver failure[J]. Biomed Res Int, 2013, 2013: 251846.
[24] Bao X,Wei J,Feng M,et al.Transplantation of human bone marrow-derived mesenchymal stem cells promotes behavioral recovery and endogenous neurogenesis after cerebral ischemia in rats[J].Br Res,2011,1367(1): 103-113.
[25] Li J,Zhu H,Liu Y,et al. Human mesenchymal stem cell transplantation protects against cerebral ischemic injury and upregulates interleukin-10 expression in Macacafascicularis[J].Br Res,2010,1334(1):65-72.
[26] 具星爱,刘滋康,郭子宽,等.肝细胞生长因子基因修饰骨髓间充质干细胞[J].中外医疗,2012,31(4):29,117.
[27] 孙广仁. 中医基础理论[M]. 北京:中国中医药出版社, 2007: 66-68.
[28] 黄帝内经.[M].7版.北京:人民卫生出版社,2013.
[29] 张金生,张宝霞.“肾精”与“干细胞”的同一性认识[J].中华中医药学刊,2018,36(2):326-328.
[30] 徐德成,马迎民,范吉平.中医“肾精”的现代医学内涵[J].中医杂志,2017,58(22):1891-1897.
[31] 孙丽芳,张丽欣,王志刚,等.干细胞治疗肝硬化的中医理论分析[J].临床合理用药杂志,2013,6(31):67-78.
[32] Wakitani S,SaitoT,Caplan AI.Myogenic cells derived from rat bone marrow mesenchymal stem cels exposed to 5-azacytidine[J].Muscle Nerve,1995,18(12):1417-1426.
[33] Reyes M,Lund T,Lenvik T,et al.Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells[J].Blood,2001,98:2615-2625.
[34] Mark F Pittenger,Alastair M Macay,Stephen C Bec,et al.Multili-neagepotential of adult human mesenchymal stem cells[J].Science,1999,284(5411):143-147.
[35] J Sanchenz-Ramos S,Song F,Cardozo Pelaez C,et al.Adult bone marrows tromal cells different iate into neural cells invi tro[J].ExpNeurol,2000,164(2):247-256.
[36] Jiang Y,Jahagirdar BN,Reinhardt RL,et al.Pluripotency of mesenchymal stem cells derive from adut marrow[J].Nature,2012,418(6893):41-49.
[37] 许静,张晶晶,郭非非,等. 淫羊藿黄酮类主要成分促进骨髓间充质干细胞向成骨细胞增殖分化作用及机制的影响[J]. 中国实验方剂学杂志,2017(14):113-120.
[38] 汪宏锦,李晶晶,柯慧,等.中药对神经干细胞增殖分化信号通路的综合调控作用分析[J].中国中药杂志,2017,42(21):4093-4103.
[39] 王玉莹,梁喜才,王雅萌,等.蛇床子素上调miR-9促进神经干细胞分化的研究[J].中药药理与临床,2018,34(1):44-48.
[40] 郜峦,王键,程发峰,等.益气活血化痰中药复方对大鼠胚胎神经干细胞生长分化增殖的影响机制研究[J].北京中医药大学学报,2016,39(2):113-118.
[41] Zhu XK, Zhu BD,Liu J,et al.Study on SCF production of bone marrow stromal cell stimulated with astragalus mere-branaceus in anemic mice[J].Pharmacol Clin Chin Mater Med(中药药理与临床),2001,17(5):19-20.
[42] Liu Ch,Liu P,Hu YY,et al.Progress of clinical and basic research on liver fibrosis with traditional Chinese medicine[J].Wold Sci Technol-Modern Tradit Chin Med,2007,9(2):112-118.
[43] 那坤.柔肝颗粒对肝纤维化大鼠TGFβ1/Smads信号转导通路的影响[D].哈尔滨:黑龙江中医药大学,2010.
[44] 赵永忠,韦铮武,漆志平,等.荔枝核总黄酮对肝纤维化大鼠肿瘤坏死因子相关凋亡诱导配体表达的影响[J].中国中西医结合消化杂志,2010,18(4):223-226.
[45] 徐列明.中医药抗肝纤维化疗效评价的探索[J].临床肝胆病杂志,2017,33(5):825-828.
[46] 李伟建,杨秋蕊,王振宇,等.生物人工肝的研究现状与进展[J].肝脏,2018,23(1):80-83.