关于子宫内膜异位症发病机制与肠道菌群关系的思考
|
摘要
子宫内膜异位症(简称内异症)作为困扰育龄期女性健康的多发性疾病,近几年来发病率逐年上升,且趋于年轻化。目前,内异症的发病机制尚不完全清楚,治愈率不高且极易复发。近年来研究表明人体是由大量微生物组成的共生体,尤其是肠道内微生物与机体健康密切相关。该文以内异症前期研究为基础,提出其发病机制可能与患者肠道微生物紊乱有关,为寻找内异症的治疗方法提供新思路与参考。
Endometriosis is a multiple disease that afflicts the health of women at childbearing age,and its incidence rate has been increasing year by year, furthermore, there has been a trend to be younger. At present,the pathogenesis of endometriosis has been not expounded completely,its cure rate is not high with high recurrence rate. In recent years,studies have shown that the human is a commensal body composed of a large number of microorganisms,and especially the microorganisms in the intestinal are closely related to the health of the body. Based on the previous studies on endometriosis,this paper proposes that its pathogenesis may be related to intestinal microbiological disorder,and aims to provide new ideas for the treatment of endometriosis.
Endometriosis is a multiple disease that afflicts the health of women at childbearing age,and its incidence rate has been increasing year by year, furthermore, there has been a trend to be younger. At present,the pathogenesis of endometriosis has been not expounded completely,its cure rate is not high with high recurrence rate. In recent years,studies have shown that the human is a commensal body composed of a large number of microorganisms,and especially the microorganisms in the intestinal are closely related to the health of the body. Based on the previous studies on endometriosis,this paper proposes that its pathogenesis may be related to intestinal microbiological disorder,and aims to provide new ideas for the treatment of endometriosis.
引文
[1] Park S,Lim W,Bazer F W,et al. Apigenin induces ROSdependent apoptosis and ER stress in human endometriosis cells[J]. J Cell Physiol,2018,233(4):3055-3065.
[2] Schindler A E. Dienogest in long-term treatment of endometriosis[J]. Int J Womens Health,2011,3(1):175-184.
[3] Strowitzki T,Marr J,Gerlinger C,et al. Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis:a 24-week,randomized,multicentre,open-label trial[J]. Hum Reprod,2010,25(3):633-641.
[4] Mcleod B S, Retzloff M G. Epidemiology of endometriosis:an assessment of risk factors[J]. Clin Obstet Gynecol,2010,53(2):389-396.
[5] Giudice L C,KAO L C. Endometriosis[J]. Lancet,2004,364(9447):1789-1799.
[6] Giudice L C. Clinical practice:endometriosis[J]. N Engl J Med,2010,362(25):2389-2398.
[7]郎景和.关于子宫内膜异位症的再认识及其意义[J].中国工程科学,2009,11(10):137-142.
[8] HUANG H Y,ZHANG Z J,CAO C B,et al. The TLR4/NF-κB signaling pathway mediates the growth of colon cancer[J]. Eur Rev Med Pharmacol Sci,2014,18(24):3834-3843.
[9] TANG X,ZHU Y. TLR4 signaling promotes immune escape of human colon cancer cells by inducing immunosuppressive cytokines and apoptosis resistance[J]. Oncol Res,2012,20(1):15-24.
[10] Kobayashi H,Kajihara H,Yamada Y,et al. Risk of carcinoma in women with ovarian endometrioma[J].Front Biosci,2011,3(2):529-539.
[11] Espin J C. Gut microbiota,diet and health.(We and our gut microbes)[J]. Mol Nutr Food Res,2017,61(1):1770015.
[12] CHONG E S. A potential role of probiotics in colorectal cancer prevention:review of possible mechanisms of action[J]. World J Microbiol Biotechnol,2014,30(2):351-374.
[13] WU X F,LIAN N Q,LU C F,et al. Research progress on effect of intestinal flora on chronic liver diseases[J].Chin Pharmacol Bull,2013,29(12):1644-1647.
[14] Sasmita A O,LING A,Voon K,et al. Madecassoside activates antineuroinflammatory mechanisms by inhibiting lipopolysaccharideinduced microglial inflammation[J]. Int J Mol Med,2018,41(5):3033-3040.
[15] LIANG B,WU L,XU H,et al. Efficacy,safety and recurrence of new progestins and selective progesterone receptor modulator for the treatment of endometriosis:a comparison study in mice[J]. Reprod Biol Endocrinol,2018,doi:10. 1186/s12958-018-0347-9.
[16] Miller J E,Monsanto S P,Ahn S H,et al. Interleukin-33modulates inflammation in endometriosis[J]. Sci Rep,2017,7(1):17903.
[17] Nomani L,Calhoun B C,Biscotti C V,et al.Endosalpingiosis of axillary lymph nodes:a rare histopathologic pitfall with clinical relevance for breast cancer staging[J]. Case Rep Pathol,2016,doi:10. 1155/2016/2856358.
[18] Salim E I,Harras S F,Abdalla A G,et al. Syphacia muris infection in rats attenuates colorectal carcinogenesis through oxidative stress and gene expression alterations. Implications for modulatory effects by Bryostatin-1[J]. Acta Parasitol,2018,63(1):198-209.
[19] WANG D,LI Y,ZHANG C,et al. MiR-216a-3p inhibits colorectal cancer cell proliferation through direct targeting COX-2 and ALOX5[J]. J Cell Biochem,2018,119(2):1755-1766.
[20] Palócz O,Pászti-Gere E,Gálfi P,et al. Chlorogenic acid combined with lactobacillus plantarum 2142 reduced LPS-induced intestinal inflammation and oxidative stress in IPEC-J2 cells[J]. PLo S One, 2016, 11(11):e0166642.
[21] Rossi E L,Khatib S A,Doerstling S S,et al. Resveratrol inhibits obesity-associated adipose tissue dysfunction and tumor growth in a mouse model of postmenopausal claudin-low breast cancer[J]. Mol Carcinog,2017,57(3):393-407.
[22] Srinivasan R,Chaitanyakumar A,Mageswari A,et al.Oral administration of lyophilized Dunaliella salina,a carotenoid-rich marine alga,reduces tumor progression in mammary cancer induced rats[J]. Food Funct,2017,8(12):4517-4527.
[23] Lim H Y,Joo H J,Choi J H,et al. Increased expression of cyclooxygenase-2 protein in human gastric carcinoma[J]. Clin Cancer Res,2000,6(2):519-525.
[24] Bose S,SONG M Y,Nam J K,et al. In vitro and in vivo protective effects of fermented preparations of dietary herbs against lipopolysaccharide insult[J]. Food Chem,2012,134(2):758-765.
[25] Dethlefsen L,McFall-Ngai M,Relman D A. An ecological and evolutionary perspective on humanmicrobe mutualism and disease[J]. Nature,2007,449(7164):811-818.
[26] Turnbaugh P J,Ley R E,Mahowald M A,et al. An obesity-associated gut microbiome with increased capacity for energy harvest[J]. Nature,2006,444(7122):1027-1031.
[27] Cani P D,Bibiloni R,Knauf C,et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice[J]. Diabetes,2008,57(6):1470-1481.
[28] Cani P D,Possemiers S,Wiele T V D,et al. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability[J]. Gut,2009,58(8):1091-1103.
[29] Goodman A L,Kallstrom G,Faith J J,et al. Extensive personal human gut microbiota culture collections characterized and manipulated in gnotobiotic mice[J].Proc Natl Acad Sci USA,2011,108(15):6252-6257.
[30] Cani P D,Amar J,Iglesias M A,et al. Metabolic endotoxemia initiates obesity and insulin resistance[J].Diabetes,2007,56(7):1761-1772.
[31] Wellen K E,Hotamisligil G S. Inflammation,stress,and diabetes[J]. J Clin Invest,2005,115(5):1111-1119.
[32] Yucel C,Karatoprak G S,Aktas Y. Nanoliposomal resveratrol as a novel approach to treatment of diabetes mellitus[J]. J Nanosci Nanotechnol,2018,18(6):3856-3864.
[33] Biarc J,Nguyen I S,Pini A,et al. Carcinogenic properties of proteins with pro-inflammatory activity from Streptococcus infantarius(formerly S. bovis)[J].Carcinogenesis,2004,25(8):1477-1484.
[34] Savagner P. Leaving the neighborhood:molecular mechanisms involved during epithelial-mesenchymal transition[J]. Bioessays,2001,23(10):912-923.
[35] Lee J M,Dedhar S,Kalluri R,et al. The epithelialmesenchymal transition:new insights in signaling,development,and disease[J]. J Cell Biol,2006,172(7):973-982.
[36] Chung J K,Park S A,Hwang H S,et al. Effects of exogenous recombinant human bone morphogenic protein-7 on the corneal epithelial mesenchymal transition and fibrosis[J]. Int J Ophthalmol,2017,10(3):329-335.
[37] XIONG W,ZHANG L,YU L,et al. Estradiol promotes cells invasion by activatingβ-catenin signaling pathway in endometriosis[J]. Reproduction,2015,150(6):507-516.
[38] XIONG W,ZHANG L,XIONG Y,et al. Hypoxia promotes invasion of endometrial stromal cells via hypoxia-inducible factor 1αupregulation-mediatedβ-catenin activation in endometriosis[J]. Reprod Sci,2015,23(4):531-541.
[39] De C B,Berx G. Regulatory networks defining EMT during cancer initiation and progression[J]. Nat Rev Cancer,2013,13(2):97-110.
[40] MA Y,LIU H,ZHANG H,et al. The TGF-βsignaling pathway induced EMT in breast cancer[J]. APSB,2015,50(4):385-392.
[41] YING J,ZHOU H Y,LIU P,et al. Aspirin inhibited the metastasis of colon cancer cells by inhibiting the expression of toll-like receptor 4[J]. Cell Biosci,2018,doi:10. 1186/s13578-017-0198-7.
[42] de La Serre C B,Ellis C L,Lee J,et al. Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation[J].Am J Physiol Gastrointest Liver Physiol,2010,299(2):G440-G448.
[43] GAO Z G,GUO B M,GAO R Y,et al. Microbiota disbiosis is associated with colorectal cancer[J]. Front Microbiol,2015,doi:10. 3389/fmicb. 2015. 00020.
[44] ZHAO L,ZHANG X,ZUO T,et al. The composition of colonic commensal bacteria according to anatomical localization in colorectal cancer[J]. Engineering,2017,3(1):90-97.
[45] Lazarovitch T,Shango M,Levine M,et al. The relationship between the new taxonomy of Streptococcus bovis,and its clonality to colon cancer,endocarditis,and biliary disease[J]. Infection,2013,41(2):329-337.
[46] Wentling G K,Metzger P P,Dozois E J,et al. Unusual bacterial infections and colorectal carcinomaStreptococcus bovis and Clostridium septicum:report of three cases[J]. Dis Colon Rectum,2006,49(8):1223-1227.
[47] Gupta A,Madani R,Mukhtar H. Streptococcus bovis endocarditis,a silent sign for colonic tumour[J].Colorectal Dis,2010,12(3):164-171.
[48] Mcmahon A J,Auld C D,Dale B A,et al. Streptococcus bovis septicaemia associated with uncomplicated colonic carcinoma[J]. Br J Surg,1991,78(7):883-885.
[49] Harrison S,Benziger H,Koerner R. Streptococcus bovis infections,colorectal cancer and liver dysfunction[J].ANZ J Surg,2011,81(11):762-763.
[50] Wong Y C,Tay S S,Mccaughan G W,et al. Immune outcomes in the liver:is CD8 T cell fate determined by the environment?[J]. J Hepatol,2015,63(4):1005-1014.
[51] Horst A K,Neumann K,Diehl L,et al. Modulation of liver tolerance by conventional and nonconventional antigen-presenting cells and regulatory immune cells[J]. Cell Mol Immunol,2016,13(3):277-292.
[52] Scheerer C,Bauer P,Chiantera V,et al. Characterization of endometriosis-associated immune cell infiltrates(EMaICI)[J]. Arch Gynecol Obstet,2016,219(3):657-664.
[53] Wintterle S,Schreiner B,Mitsdoerffer M,et al.Expression of the B7-related molecule B7-H1 by glioma cells:a potential mechanism of immune paralysis[J].Cancer Res,2003,63(21):7462-7467.
[54] ZHANG H,ZHAO X,LIU S,et al. 17βE2 promotes cell proliferation in endometriosis by decreasing PTEN via NFκB-dependent pathway[J]. Mol Cell Endocrinol,2010,317(1/2):31-43.
[55] DAI S,JIA R,ZHANG X,et al. The PD-1/PD-Ls pathway and autoimmune diseases[J]. Cell Immunol,2014,290(1):72-79.
[56] Chikuma S. Basics of PD-1 in self-tolerance,infection,and cancer immunity[J]. Int J Clin Oncol,2016,21(3):448-455.
[57] Riella L V,Paterson A M,Sharpe A H,et al. Role of the PD-1 Pathway in the Immune Response[J]. Am J Transplant,2012,12(10):2575-2587.
[58] Okazaki T,Honjo T. The PD-1-PD-L pathway in immunological tolerance[J]. Trends Immunol,2006,27(4):195-201.
[59] DONG H,Strome S E,Salomao D R,et al. Tumorassociated B7-H1 promotes T-cell apoptosis:a potential mechanism of immune evasion[J]. Nat Med,2002,8(8):793-800.
[60] Francisco L M,Sage P T,Sharpe A H. The PD-1 pathway in tolerance and autoimmunity[J]. Immunol Rev,2010,236(1):219-242.
[61] Anderson A C,Joller N,Kuchroo V K. Lag-3,Tim-3,and TIGIT:co-inhibitory receptors with specialized functions in immune regulation[J]. Immunity,2016,44(5):989-1004.
[62] LI M,LI H,LIU F,et al. Characterization of ovarian clear cell carcinoma using target drug-based molecular biomarkers:implications for personalized cancer therapy[J]. J Ovarian Res,2017,doi:10. 1186/s13048-017-0304-9.
[63] Ceeraz S,Nowak E C,Noelle R J. B7 family checkpoint regulators in immune regulation and disease[J]. Trends Immunol,2013,34(11):556-563.
[64] Gatalica Z,Snyder C,Maney T,et al. Programmed cell death 1(PD-1)and its ligand(PD-L1)in common cancers and their correlation with molecular cancer type[J]. Cancer Epidemiol Biomarkers Prev,2014,23(12):2965-2970.
[65] Teo P Y,YANG C,Whilding L M,et al. Ovarian cancer immunotherapy using PD-L1 siRNA targeted delivery from folic acid-functionalized polyethylenimine:strategies to enhance T cell killing[J]. Adv Healthc Mater,2015,4(8):1180-1189.
[66] CHANG K K,LIU L B,JIN L P,et al. IL-27 triggers IL-10 production in Th17 cells via a c-Maf/RORγt/Blimp-1 signal to promote the progression of endometriosis[J].Cell Death Dis,2017,8(3):e2666.
[67]罗颂平.中医妇科学[M].北京:高等教育出版社,2008:257-264.
[68]林素芬.子宫内膜异位症近20年中医临床文献研究[D].广州:广州中医药大学,2013.
[69]孙秀丽,王建玲,李沛霖.中药灌肠治疗子宫内膜异位症临床研究进展[J].山西中医,2012,28(10):56-58.
[70]杜娟.莪棱灌肠液保留灌肠治疗子宫内膜异位症的临床观察[D].广州:广州中医药大学,2007.
[71]刘艳巧,刘润侠,狄灵.中药保留灌肠治疗子宫内膜异位症临床观察[J].中国中医药信息杂志,2001,8(6):63.
[72]王家华.中药复方灌肠对肠道菌群的影响研究[J].医药前沿,2014(13):366-367.
[73]张宁,李自辉,赵洪伟,等.寒凝血瘀证大鼠的肠道菌群变化与粪便代谢特征分析[J].中国实验方剂学杂志,2018,24(2):79-85.
[74] Pérez-López F R,Villagrasa-Boli P,Mu1oz-Olarte M,et al. Association between endometriosis and preterm birth in women with spontaneous conception or using assisted reproductive technology:a systematic review and metaanalysis of cohort studies[J]. Reprod Sci,2018,25(3):311-319.
[75] Park S,Lim W,Bazer F W,et al. Apigenin induces ROSdependent apoptosis and ER stress in human endometriosis cells[J]. J Cell Physiol,2018,233(4):3055-3065.
[76] Yoshino O,Yamada-Nomoto K,Kobayashi M,et al.Bradykinin system is involved in endometriosis-related pain through endothelin-1 production[J]. Eur J Pain,2018,22(3):501-510.
[77] Cuevas M,Cruz M L,Ramirez A E,et al. Stress during development of experimental endometriosis influences nerve growth and disease progression[J]. Reprod Sci,2018,25(3):347-357.
[78] ZHANG C,PENG Z,BAN D,et al. Upregulation of interleukin 35 in patients with endometriosis stimulates cell proliferation[J]. Reprod Sci,2018,25(3):443-451.
[79] LV X,WANG D,MA Y,et al. Analysis of the oncogene BRAF mutation and the correlation of the expression of wild-type BRAF and CREB1 in endometriosis[J]. Int J Mol Med,2018,41(3):1349-1356.
[80] Bashti O,Noruzinia M,Garshasbi M,et al. miR-31 and miR-145 as potential non-invasive regulatory biomarkers in patients with endometriosis[J]. Cell J,2018,20(1):84-89.
[81] HAN B,Sivaramakrishnan P,LIN C J,et al. Microbial Genetic Composition Tunes Host Longevity[J]. Cell,2017,169(7):1249-1257.
[82] Koppel N,Rekdal V M,Balskus E P. Chemical transformation of xenobiotics by the human gut microbiota[J]. Science, 2017, doi:10. 1126/science. aag2770.
[83] Cervantes-Barragan L,CHAI J N,Tianero M D,et al.Lactobacillus reuteri induces gut intraepithelial CD4+CD8αα+T cells[J]. Science,2017,357(6353):806-812.
[84]马祥雪,王凤云,符竣杰,等.基于肠道菌群的中医健脾方剂作用机制的研究现状与思考[J].中国实验方剂学杂志,2017,23(5):210-215.
[2] Schindler A E. Dienogest in long-term treatment of endometriosis[J]. Int J Womens Health,2011,3(1):175-184.
[3] Strowitzki T,Marr J,Gerlinger C,et al. Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis:a 24-week,randomized,multicentre,open-label trial[J]. Hum Reprod,2010,25(3):633-641.
[4] Mcleod B S, Retzloff M G. Epidemiology of endometriosis:an assessment of risk factors[J]. Clin Obstet Gynecol,2010,53(2):389-396.
[5] Giudice L C,KAO L C. Endometriosis[J]. Lancet,2004,364(9447):1789-1799.
[6] Giudice L C. Clinical practice:endometriosis[J]. N Engl J Med,2010,362(25):2389-2398.
[7]郎景和.关于子宫内膜异位症的再认识及其意义[J].中国工程科学,2009,11(10):137-142.
[8] HUANG H Y,ZHANG Z J,CAO C B,et al. The TLR4/NF-κB signaling pathway mediates the growth of colon cancer[J]. Eur Rev Med Pharmacol Sci,2014,18(24):3834-3843.
[9] TANG X,ZHU Y. TLR4 signaling promotes immune escape of human colon cancer cells by inducing immunosuppressive cytokines and apoptosis resistance[J]. Oncol Res,2012,20(1):15-24.
[10] Kobayashi H,Kajihara H,Yamada Y,et al. Risk of carcinoma in women with ovarian endometrioma[J].Front Biosci,2011,3(2):529-539.
[11] Espin J C. Gut microbiota,diet and health.(We and our gut microbes)[J]. Mol Nutr Food Res,2017,61(1):1770015.
[12] CHONG E S. A potential role of probiotics in colorectal cancer prevention:review of possible mechanisms of action[J]. World J Microbiol Biotechnol,2014,30(2):351-374.
[13] WU X F,LIAN N Q,LU C F,et al. Research progress on effect of intestinal flora on chronic liver diseases[J].Chin Pharmacol Bull,2013,29(12):1644-1647.
[14] Sasmita A O,LING A,Voon K,et al. Madecassoside activates antineuroinflammatory mechanisms by inhibiting lipopolysaccharideinduced microglial inflammation[J]. Int J Mol Med,2018,41(5):3033-3040.
[15] LIANG B,WU L,XU H,et al. Efficacy,safety and recurrence of new progestins and selective progesterone receptor modulator for the treatment of endometriosis:a comparison study in mice[J]. Reprod Biol Endocrinol,2018,doi:10. 1186/s12958-018-0347-9.
[16] Miller J E,Monsanto S P,Ahn S H,et al. Interleukin-33modulates inflammation in endometriosis[J]. Sci Rep,2017,7(1):17903.
[17] Nomani L,Calhoun B C,Biscotti C V,et al.Endosalpingiosis of axillary lymph nodes:a rare histopathologic pitfall with clinical relevance for breast cancer staging[J]. Case Rep Pathol,2016,doi:10. 1155/2016/2856358.
[18] Salim E I,Harras S F,Abdalla A G,et al. Syphacia muris infection in rats attenuates colorectal carcinogenesis through oxidative stress and gene expression alterations. Implications for modulatory effects by Bryostatin-1[J]. Acta Parasitol,2018,63(1):198-209.
[19] WANG D,LI Y,ZHANG C,et al. MiR-216a-3p inhibits colorectal cancer cell proliferation through direct targeting COX-2 and ALOX5[J]. J Cell Biochem,2018,119(2):1755-1766.
[20] Palócz O,Pászti-Gere E,Gálfi P,et al. Chlorogenic acid combined with lactobacillus plantarum 2142 reduced LPS-induced intestinal inflammation and oxidative stress in IPEC-J2 cells[J]. PLo S One, 2016, 11(11):e0166642.
[21] Rossi E L,Khatib S A,Doerstling S S,et al. Resveratrol inhibits obesity-associated adipose tissue dysfunction and tumor growth in a mouse model of postmenopausal claudin-low breast cancer[J]. Mol Carcinog,2017,57(3):393-407.
[22] Srinivasan R,Chaitanyakumar A,Mageswari A,et al.Oral administration of lyophilized Dunaliella salina,a carotenoid-rich marine alga,reduces tumor progression in mammary cancer induced rats[J]. Food Funct,2017,8(12):4517-4527.
[23] Lim H Y,Joo H J,Choi J H,et al. Increased expression of cyclooxygenase-2 protein in human gastric carcinoma[J]. Clin Cancer Res,2000,6(2):519-525.
[24] Bose S,SONG M Y,Nam J K,et al. In vitro and in vivo protective effects of fermented preparations of dietary herbs against lipopolysaccharide insult[J]. Food Chem,2012,134(2):758-765.
[25] Dethlefsen L,McFall-Ngai M,Relman D A. An ecological and evolutionary perspective on humanmicrobe mutualism and disease[J]. Nature,2007,449(7164):811-818.
[26] Turnbaugh P J,Ley R E,Mahowald M A,et al. An obesity-associated gut microbiome with increased capacity for energy harvest[J]. Nature,2006,444(7122):1027-1031.
[27] Cani P D,Bibiloni R,Knauf C,et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice[J]. Diabetes,2008,57(6):1470-1481.
[28] Cani P D,Possemiers S,Wiele T V D,et al. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability[J]. Gut,2009,58(8):1091-1103.
[29] Goodman A L,Kallstrom G,Faith J J,et al. Extensive personal human gut microbiota culture collections characterized and manipulated in gnotobiotic mice[J].Proc Natl Acad Sci USA,2011,108(15):6252-6257.
[30] Cani P D,Amar J,Iglesias M A,et al. Metabolic endotoxemia initiates obesity and insulin resistance[J].Diabetes,2007,56(7):1761-1772.
[31] Wellen K E,Hotamisligil G S. Inflammation,stress,and diabetes[J]. J Clin Invest,2005,115(5):1111-1119.
[32] Yucel C,Karatoprak G S,Aktas Y. Nanoliposomal resveratrol as a novel approach to treatment of diabetes mellitus[J]. J Nanosci Nanotechnol,2018,18(6):3856-3864.
[33] Biarc J,Nguyen I S,Pini A,et al. Carcinogenic properties of proteins with pro-inflammatory activity from Streptococcus infantarius(formerly S. bovis)[J].Carcinogenesis,2004,25(8):1477-1484.
[34] Savagner P. Leaving the neighborhood:molecular mechanisms involved during epithelial-mesenchymal transition[J]. Bioessays,2001,23(10):912-923.
[35] Lee J M,Dedhar S,Kalluri R,et al. The epithelialmesenchymal transition:new insights in signaling,development,and disease[J]. J Cell Biol,2006,172(7):973-982.
[36] Chung J K,Park S A,Hwang H S,et al. Effects of exogenous recombinant human bone morphogenic protein-7 on the corneal epithelial mesenchymal transition and fibrosis[J]. Int J Ophthalmol,2017,10(3):329-335.
[37] XIONG W,ZHANG L,YU L,et al. Estradiol promotes cells invasion by activatingβ-catenin signaling pathway in endometriosis[J]. Reproduction,2015,150(6):507-516.
[38] XIONG W,ZHANG L,XIONG Y,et al. Hypoxia promotes invasion of endometrial stromal cells via hypoxia-inducible factor 1αupregulation-mediatedβ-catenin activation in endometriosis[J]. Reprod Sci,2015,23(4):531-541.
[39] De C B,Berx G. Regulatory networks defining EMT during cancer initiation and progression[J]. Nat Rev Cancer,2013,13(2):97-110.
[40] MA Y,LIU H,ZHANG H,et al. The TGF-βsignaling pathway induced EMT in breast cancer[J]. APSB,2015,50(4):385-392.
[41] YING J,ZHOU H Y,LIU P,et al. Aspirin inhibited the metastasis of colon cancer cells by inhibiting the expression of toll-like receptor 4[J]. Cell Biosci,2018,doi:10. 1186/s13578-017-0198-7.
[42] de La Serre C B,Ellis C L,Lee J,et al. Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation[J].Am J Physiol Gastrointest Liver Physiol,2010,299(2):G440-G448.
[43] GAO Z G,GUO B M,GAO R Y,et al. Microbiota disbiosis is associated with colorectal cancer[J]. Front Microbiol,2015,doi:10. 3389/fmicb. 2015. 00020.
[44] ZHAO L,ZHANG X,ZUO T,et al. The composition of colonic commensal bacteria according to anatomical localization in colorectal cancer[J]. Engineering,2017,3(1):90-97.
[45] Lazarovitch T,Shango M,Levine M,et al. The relationship between the new taxonomy of Streptococcus bovis,and its clonality to colon cancer,endocarditis,and biliary disease[J]. Infection,2013,41(2):329-337.
[46] Wentling G K,Metzger P P,Dozois E J,et al. Unusual bacterial infections and colorectal carcinomaStreptococcus bovis and Clostridium septicum:report of three cases[J]. Dis Colon Rectum,2006,49(8):1223-1227.
[47] Gupta A,Madani R,Mukhtar H. Streptococcus bovis endocarditis,a silent sign for colonic tumour[J].Colorectal Dis,2010,12(3):164-171.
[48] Mcmahon A J,Auld C D,Dale B A,et al. Streptococcus bovis septicaemia associated with uncomplicated colonic carcinoma[J]. Br J Surg,1991,78(7):883-885.
[49] Harrison S,Benziger H,Koerner R. Streptococcus bovis infections,colorectal cancer and liver dysfunction[J].ANZ J Surg,2011,81(11):762-763.
[50] Wong Y C,Tay S S,Mccaughan G W,et al. Immune outcomes in the liver:is CD8 T cell fate determined by the environment?[J]. J Hepatol,2015,63(4):1005-1014.
[51] Horst A K,Neumann K,Diehl L,et al. Modulation of liver tolerance by conventional and nonconventional antigen-presenting cells and regulatory immune cells[J]. Cell Mol Immunol,2016,13(3):277-292.
[52] Scheerer C,Bauer P,Chiantera V,et al. Characterization of endometriosis-associated immune cell infiltrates(EMaICI)[J]. Arch Gynecol Obstet,2016,219(3):657-664.
[53] Wintterle S,Schreiner B,Mitsdoerffer M,et al.Expression of the B7-related molecule B7-H1 by glioma cells:a potential mechanism of immune paralysis[J].Cancer Res,2003,63(21):7462-7467.
[54] ZHANG H,ZHAO X,LIU S,et al. 17βE2 promotes cell proliferation in endometriosis by decreasing PTEN via NFκB-dependent pathway[J]. Mol Cell Endocrinol,2010,317(1/2):31-43.
[55] DAI S,JIA R,ZHANG X,et al. The PD-1/PD-Ls pathway and autoimmune diseases[J]. Cell Immunol,2014,290(1):72-79.
[56] Chikuma S. Basics of PD-1 in self-tolerance,infection,and cancer immunity[J]. Int J Clin Oncol,2016,21(3):448-455.
[57] Riella L V,Paterson A M,Sharpe A H,et al. Role of the PD-1 Pathway in the Immune Response[J]. Am J Transplant,2012,12(10):2575-2587.
[58] Okazaki T,Honjo T. The PD-1-PD-L pathway in immunological tolerance[J]. Trends Immunol,2006,27(4):195-201.
[59] DONG H,Strome S E,Salomao D R,et al. Tumorassociated B7-H1 promotes T-cell apoptosis:a potential mechanism of immune evasion[J]. Nat Med,2002,8(8):793-800.
[60] Francisco L M,Sage P T,Sharpe A H. The PD-1 pathway in tolerance and autoimmunity[J]. Immunol Rev,2010,236(1):219-242.
[61] Anderson A C,Joller N,Kuchroo V K. Lag-3,Tim-3,and TIGIT:co-inhibitory receptors with specialized functions in immune regulation[J]. Immunity,2016,44(5):989-1004.
[62] LI M,LI H,LIU F,et al. Characterization of ovarian clear cell carcinoma using target drug-based molecular biomarkers:implications for personalized cancer therapy[J]. J Ovarian Res,2017,doi:10. 1186/s13048-017-0304-9.
[63] Ceeraz S,Nowak E C,Noelle R J. B7 family checkpoint regulators in immune regulation and disease[J]. Trends Immunol,2013,34(11):556-563.
[64] Gatalica Z,Snyder C,Maney T,et al. Programmed cell death 1(PD-1)and its ligand(PD-L1)in common cancers and their correlation with molecular cancer type[J]. Cancer Epidemiol Biomarkers Prev,2014,23(12):2965-2970.
[65] Teo P Y,YANG C,Whilding L M,et al. Ovarian cancer immunotherapy using PD-L1 siRNA targeted delivery from folic acid-functionalized polyethylenimine:strategies to enhance T cell killing[J]. Adv Healthc Mater,2015,4(8):1180-1189.
[66] CHANG K K,LIU L B,JIN L P,et al. IL-27 triggers IL-10 production in Th17 cells via a c-Maf/RORγt/Blimp-1 signal to promote the progression of endometriosis[J].Cell Death Dis,2017,8(3):e2666.
[67]罗颂平.中医妇科学[M].北京:高等教育出版社,2008:257-264.
[68]林素芬.子宫内膜异位症近20年中医临床文献研究[D].广州:广州中医药大学,2013.
[69]孙秀丽,王建玲,李沛霖.中药灌肠治疗子宫内膜异位症临床研究进展[J].山西中医,2012,28(10):56-58.
[70]杜娟.莪棱灌肠液保留灌肠治疗子宫内膜异位症的临床观察[D].广州:广州中医药大学,2007.
[71]刘艳巧,刘润侠,狄灵.中药保留灌肠治疗子宫内膜异位症临床观察[J].中国中医药信息杂志,2001,8(6):63.
[72]王家华.中药复方灌肠对肠道菌群的影响研究[J].医药前沿,2014(13):366-367.
[73]张宁,李自辉,赵洪伟,等.寒凝血瘀证大鼠的肠道菌群变化与粪便代谢特征分析[J].中国实验方剂学杂志,2018,24(2):79-85.
[74] Pérez-López F R,Villagrasa-Boli P,Mu1oz-Olarte M,et al. Association between endometriosis and preterm birth in women with spontaneous conception or using assisted reproductive technology:a systematic review and metaanalysis of cohort studies[J]. Reprod Sci,2018,25(3):311-319.
[75] Park S,Lim W,Bazer F W,et al. Apigenin induces ROSdependent apoptosis and ER stress in human endometriosis cells[J]. J Cell Physiol,2018,233(4):3055-3065.
[76] Yoshino O,Yamada-Nomoto K,Kobayashi M,et al.Bradykinin system is involved in endometriosis-related pain through endothelin-1 production[J]. Eur J Pain,2018,22(3):501-510.
[77] Cuevas M,Cruz M L,Ramirez A E,et al. Stress during development of experimental endometriosis influences nerve growth and disease progression[J]. Reprod Sci,2018,25(3):347-357.
[78] ZHANG C,PENG Z,BAN D,et al. Upregulation of interleukin 35 in patients with endometriosis stimulates cell proliferation[J]. Reprod Sci,2018,25(3):443-451.
[79] LV X,WANG D,MA Y,et al. Analysis of the oncogene BRAF mutation and the correlation of the expression of wild-type BRAF and CREB1 in endometriosis[J]. Int J Mol Med,2018,41(3):1349-1356.
[80] Bashti O,Noruzinia M,Garshasbi M,et al. miR-31 and miR-145 as potential non-invasive regulatory biomarkers in patients with endometriosis[J]. Cell J,2018,20(1):84-89.
[81] HAN B,Sivaramakrishnan P,LIN C J,et al. Microbial Genetic Composition Tunes Host Longevity[J]. Cell,2017,169(7):1249-1257.
[82] Koppel N,Rekdal V M,Balskus E P. Chemical transformation of xenobiotics by the human gut microbiota[J]. Science, 2017, doi:10. 1126/science. aag2770.
[83] Cervantes-Barragan L,CHAI J N,Tianero M D,et al.Lactobacillus reuteri induces gut intraepithelial CD4+CD8αα+T cells[J]. Science,2017,357(6353):806-812.
[84]马祥雪,王凤云,符竣杰,等.基于肠道菌群的中医健脾方剂作用机制的研究现状与思考[J].中国实验方剂学杂志,2017,23(5):210-215.