基于肝-肠轴探讨“实脾法”治疗肝癌的科学内涵
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摘要
肝和脾在生理、病理上有密切的联系,"实脾法"治疗肝癌是中医整体观念和"治未病"的重要体现,历代医家在此基础上论治肝病成效显著。随着肝-肠轴学说研究的深入,发现通过胃肠道多种途径调节肝-肠轴上行通道,如肠道黏膜屏障、内毒素、肠道菌群等对肝功能均具有调节作用。大量的证据表明,调节肠道稳态是治疗肝癌等肝病的潜在途径,从中医理论出发,结合临床应用,并联系肝-肠轴学说,探讨"实脾法"在原发性肝癌治疗中的科学内涵。
The liver and spleen are closely related in physiology and pathology. The"reinforcing spleen method"for the treatment of liver cancer is an important manifestation of the holistic concept and the preventive treatment of diseases in traditional Chinese medicine( TCM). Generations of physicians have been effectively treating liver disease with this method. Along with in-depth study of the theory of gut-liver axis,it was found that gastrointestinal tract can adjust the liver function through several ways of gut-liver axis uplink channels,such as intestinal mucosa barrier,endotoxins,intestinal flora,having liver-regulating function. More and more evidence shows that regulating intestinal homeostasis is the potential pathways in treating liver cancer and other liver diseases. Therefore,this paper from the theory of TCM,combined with clinical application,and linked to the theory of gut-liver axis,aimed to explore the scientific connotation of "reinforcing spleen method"in the treatment of primary liver cancer.
The liver and spleen are closely related in physiology and pathology. The"reinforcing spleen method"for the treatment of liver cancer is an important manifestation of the holistic concept and the preventive treatment of diseases in traditional Chinese medicine( TCM). Generations of physicians have been effectively treating liver disease with this method. Along with in-depth study of the theory of gut-liver axis,it was found that gastrointestinal tract can adjust the liver function through several ways of gut-liver axis uplink channels,such as intestinal mucosa barrier,endotoxins,intestinal flora,having liver-regulating function. More and more evidence shows that regulating intestinal homeostasis is the potential pathways in treating liver cancer and other liver diseases. Therefore,this paper from the theory of TCM,combined with clinical application,and linked to the theory of gut-liver axis,aimed to explore the scientific connotation of "reinforcing spleen method"in the treatment of primary liver cancer.
引文
[1]WAN MLY,EL-NEZAMI H. Targeting gut microbiota in hepatocellular carcinoma:probiotics as a novel therapy[J]. Hepatobiliary Surg Nutri,2018,7(1):11-20.
[2]TORRE LA,BRAY F,SIEGEL RL,et al. Global cancer statistics,2012[J]. CA Cancer J Clin,2015,65(2):87-108.
[3]CHEN W,ZHENG R,BAADE PD,et al. Cancer statistics in China,2015[J]. CA Cancer J Clin,2016,66(2):115-132.
[4]张建伟,王苹.《金匮要略》“见肝之病,知肝传脾,当先实脾”之管见[J].甘肃中医学院学报,2012,29(1):21-23.
[5]彭学钱,王三虎.从“肝脾相关”论治肝癌并发低血糖[J].中医学报,2016,31(12):1826-1829.
[6]林靖,周岱翰.周岱翰对肝癌病的辨治思路[J].辽宁中医杂志,2016,43(8):1640-1643.
[7]曲倩倩.李秀荣运用实脾法治疗肝癌经验[J].山东中医药大学学报,2015,39(1):66-67.
[8]刘巧红.李素领教授一补四攻法治疗中晚期肝癌的经验[J].环球中医药,2018,11(3):400-402.
[9]岳煜.薛博瑜教授辨治肝癌四法经验探析[J].环球中医药,2016,9(1):56-57.
[10]MARSHELL JC. The gut as a potential trigger of exerciseinduced inflammatory responses[J]. Can J Physiol Pharmacol,1998,76(5):479-484.
[11]ZEUZEM S. Gut-liver axis[J]. Int J Colorectal Dis,2000,15(2):59-82.
[12]刘玉兰.整合肝肠病学-肝肠对话[M].北京:人民卫生出版社,2014:122.
[13]STRKEL P,LECLERCQ S,DE TIMARY P,et al. Intestinal dysbiosis and permeability:the yin and yang in alcohol dependence and alcoholic liver disease[J]. Clin Sci,2018,132(2):199-212.
[14]杨天翼.健脾化湿解毒方对诱导的急性肝衰竭小鼠模型的影响[D].北京:北京中医药大学,2013:16-18.
[15]CHEN P. Enteric dysbiosis,Gut barrier and liver disease[J]. Hepatobiliary Surg Nutri,2018,7(1):38-40.
[16]黄玉珍.参苓白术散对脾虚泄泻幼鼠模型肠黏膜屏障的影响[D].南京:南京中医药大学,2016.
[17]施旭光,曼婷,邓淙友,等.补中益气汤及其配伍对脾虚大鼠胃黏膜保护作用机制研究[J].现代中医药,2013,33(5):114-117.
[18]朱珊.健脾止泻颗粒对脾虚泄泻小鼠肠道菌群和小肠黏膜的作用[J].北京中医药大学学报,2003,6(3):28-30.
[19]TAJIRI K,SHIMIZU Y. Gut bacteria may control development of hepatocellular carcinoma[J]. Hepatobiliary Surg Nutr,2017,6(6):417-419.
[20]ORCI LA,LACOTTE S,DELAUNE V,et al. Effects of the gut-liver axis on ischaemia-mediated hepatocellular carcinoma recurrence in the mouse liver[J]. J Hepatol,2018,68(5):978-985.
[21]ZHANG HL,YU LX,YANG W,et al. Profound impact of gut homeostasis on chemically-induced pro-tumorigenic inflammation and hepatocarcinogenesis in rats[J]. J Hepatol,2012,57(4):803-812.
[22]FUKUI H. Improve gut microbiome:a new horizon of cancer therapy[J]. Hepatobiliary Surg Nutr,2017,6(6):424-428.
[23]刘业方,李钰,王小莉.中医药调节肝硬化肠道微生态研究进展[J].云南中医中药杂志,2017,38(9):76-78.
[24]朱珊.健脾止泻颗粒对脾虚泄泻小鼠微生态及小肠和胸腺超微结构影响的实验研究[J].中国医药学报,2003,18(7):419-422.
[25]LI S,WU WC,HE CY,et al. Change of intestinal mucosa barrier function in the progress of non-alcoholic steatohepatitis in rats[J]. World J Gastroenterol,2008,14(20):3254-3258.
[26]OKADA N,SANADA Y,URAHASHI T,et al. Endotoxin metabolism reflects hepatic functional reserve in end-stage liver disease[J]. Transplant Proc,2018,50(5):1360-1364.
[27]YU LX,YAN HX,LIU Q,et al. Endotoxin accumulation prevents carcinogen-induced apoptosis and promotes liver tumorigenesis in rodents[J]. Hepatology,2010,52(4):1322-1333.
[28]陈斌,徐嘉蔚,彭杰,等.基于逍遥散及其拆方研究“肝病实脾法”对肝纤维化大鼠肠道菌群的影响[J].临床肝胆病杂志,2016,2(4):657-662.
[29]刘晓琳.肝脾舒对肝硬化大鼠内毒素血症的影响[J].中国实用医药,2015,10(9):288-289.
[30]何琬,陈斌,徐嘉蔚,等.“肝病实脾”法对ACLF大鼠内毒素血症的影响[J].湖南中医药大学学报,2015,35(3):12-15.
[2]TORRE LA,BRAY F,SIEGEL RL,et al. Global cancer statistics,2012[J]. CA Cancer J Clin,2015,65(2):87-108.
[3]CHEN W,ZHENG R,BAADE PD,et al. Cancer statistics in China,2015[J]. CA Cancer J Clin,2016,66(2):115-132.
[4]张建伟,王苹.《金匮要略》“见肝之病,知肝传脾,当先实脾”之管见[J].甘肃中医学院学报,2012,29(1):21-23.
[5]彭学钱,王三虎.从“肝脾相关”论治肝癌并发低血糖[J].中医学报,2016,31(12):1826-1829.
[6]林靖,周岱翰.周岱翰对肝癌病的辨治思路[J].辽宁中医杂志,2016,43(8):1640-1643.
[7]曲倩倩.李秀荣运用实脾法治疗肝癌经验[J].山东中医药大学学报,2015,39(1):66-67.
[8]刘巧红.李素领教授一补四攻法治疗中晚期肝癌的经验[J].环球中医药,2018,11(3):400-402.
[9]岳煜.薛博瑜教授辨治肝癌四法经验探析[J].环球中医药,2016,9(1):56-57.
[10]MARSHELL JC. The gut as a potential trigger of exerciseinduced inflammatory responses[J]. Can J Physiol Pharmacol,1998,76(5):479-484.
[11]ZEUZEM S. Gut-liver axis[J]. Int J Colorectal Dis,2000,15(2):59-82.
[12]刘玉兰.整合肝肠病学-肝肠对话[M].北京:人民卫生出版社,2014:122.
[13]STRKEL P,LECLERCQ S,DE TIMARY P,et al. Intestinal dysbiosis and permeability:the yin and yang in alcohol dependence and alcoholic liver disease[J]. Clin Sci,2018,132(2):199-212.
[14]杨天翼.健脾化湿解毒方对诱导的急性肝衰竭小鼠模型的影响[D].北京:北京中医药大学,2013:16-18.
[15]CHEN P. Enteric dysbiosis,Gut barrier and liver disease[J]. Hepatobiliary Surg Nutri,2018,7(1):38-40.
[16]黄玉珍.参苓白术散对脾虚泄泻幼鼠模型肠黏膜屏障的影响[D].南京:南京中医药大学,2016.
[17]施旭光,曼婷,邓淙友,等.补中益气汤及其配伍对脾虚大鼠胃黏膜保护作用机制研究[J].现代中医药,2013,33(5):114-117.
[18]朱珊.健脾止泻颗粒对脾虚泄泻小鼠肠道菌群和小肠黏膜的作用[J].北京中医药大学学报,2003,6(3):28-30.
[19]TAJIRI K,SHIMIZU Y. Gut bacteria may control development of hepatocellular carcinoma[J]. Hepatobiliary Surg Nutr,2017,6(6):417-419.
[20]ORCI LA,LACOTTE S,DELAUNE V,et al. Effects of the gut-liver axis on ischaemia-mediated hepatocellular carcinoma recurrence in the mouse liver[J]. J Hepatol,2018,68(5):978-985.
[21]ZHANG HL,YU LX,YANG W,et al. Profound impact of gut homeostasis on chemically-induced pro-tumorigenic inflammation and hepatocarcinogenesis in rats[J]. J Hepatol,2012,57(4):803-812.
[22]FUKUI H. Improve gut microbiome:a new horizon of cancer therapy[J]. Hepatobiliary Surg Nutr,2017,6(6):424-428.
[23]刘业方,李钰,王小莉.中医药调节肝硬化肠道微生态研究进展[J].云南中医中药杂志,2017,38(9):76-78.
[24]朱珊.健脾止泻颗粒对脾虚泄泻小鼠微生态及小肠和胸腺超微结构影响的实验研究[J].中国医药学报,2003,18(7):419-422.
[25]LI S,WU WC,HE CY,et al. Change of intestinal mucosa barrier function in the progress of non-alcoholic steatohepatitis in rats[J]. World J Gastroenterol,2008,14(20):3254-3258.
[26]OKADA N,SANADA Y,URAHASHI T,et al. Endotoxin metabolism reflects hepatic functional reserve in end-stage liver disease[J]. Transplant Proc,2018,50(5):1360-1364.
[27]YU LX,YAN HX,LIU Q,et al. Endotoxin accumulation prevents carcinogen-induced apoptosis and promotes liver tumorigenesis in rodents[J]. Hepatology,2010,52(4):1322-1333.
[28]陈斌,徐嘉蔚,彭杰,等.基于逍遥散及其拆方研究“肝病实脾法”对肝纤维化大鼠肠道菌群的影响[J].临床肝胆病杂志,2016,2(4):657-662.
[29]刘晓琳.肝脾舒对肝硬化大鼠内毒素血症的影响[J].中国实用医药,2015,10(9):288-289.
[30]何琬,陈斌,徐嘉蔚,等.“肝病实脾”法对ACLF大鼠内毒素血症的影响[J].湖南中医药大学学报,2015,35(3):12-15.