瞬时感受器电位香草酸受体1在胃食管反流病中的研究进展
摘要
胃食管反流病(gastroesophageal reflux disease,GERD)是一种食管胃动力性疾病,主要临床表现为烧心、胸闷、胸骨后疼痛等。瞬时受体电位香草酸受体1(transient receptor potential vanilloid 1,TRPV1)属于瞬时受体电位离子通道家族成员,为伤害性感受器,可被化学刺激(pH>6.8等)或热刺激(>43℃等)激活。研究发现TRPV1与GERD临床表现密切相关。通过对TRPV1的深入研究,有助于理解GERD病理生理机制和开发新型治疗药物。本文就食管中TRPV1在GERD中的研究进展作一综述。
引文
[1]Zou D,He J,Ma X,et al.Epidemiology of symptom-defined gastroesophageal reflux diase and reflux esophagitis:the systematicinvestigation of gastrointestinal diseases in China(SILC)[J].Dis Esophagus,2011,46(2):133-141.DOI:10.3109/00365521.2010.521888.
[2]Dhaliwal J.Epidemiology of gastro-oesophageal reflux disease:a systematic review[J].Gut,2014,63(6):710-717.DOI:10.1136/gut.2004.051821
[3]Ronkainen J,Aro P,Storskrubb T,et al.High prevalence of gastroesophageal reflux symptoms and esophagitis with or without symptoms in the general adult Swedish population:a Kalixanda study report[J].Scand J Gastroenterol,2005,40(3):275-285.DOI:10.1080/00365520510011579
[4]Kim N,Lee SW,Cho SI,et al.The prevalence of and risk factors for erosive oesophagitis and non-erosive reflux disease:a nationwide multicentre prospective study in Korea[J].Aliment Pharmacol Ther,2008,27(2):173-185.DOI:10.1111/j.1365-2036.2007.03561.x
[5]Horii T,Koike T,Abe Y,et al.Two distinct types of cancer of different origin may be mixed in gastroesophageal junction adenocarcinomas in Japan:Evidence from direct evaluation of gastric acid secretion[J].Scandinavian Journal of Gastroenterology,2011,46(6):710-719.DOI:10.3109/00365521.2011.565069
[6]王昭金,王延清.VR1受体在大鼠食管传入纤维的表达[J].解剖学报,2005,36(6):675-678.DOI:10.3321/j.issn:0529-1356.2005.06.022
[7]王凯,程鹏,王亚雷.TRPV1受体在胃食管反流病患者食管黏膜的表达及其与症状的关系[J].安徽医学,2012,33(2):140-143.DOI:10.3969/j.issn.1000-0399.2012.02.004.
[8]Guarino MPL,Cheng L,Ma J,et al.Increased TRPV1 gene expression in esophageal mucosa of patients with non-erosive and erosive reflux disease[J].Neurogastroenterol Motil,2010,22:746-751.DOI:10.1111/j.1365-2982.2010.01514.x.
[9]Savarino E,Tutuian R,Zentilin P,et al.Characteristics of reflux episodes and symptom association in patients with erosive esophagitis and nonerosive reflux disease:study using combined impedance-p H off therapy[J].Am J Gastroenterol,2009,105:1053-1061.DOI:10.1038/ajg.2009.670.
[10]de Bortoli N,Martinucci I,Savarino E,et al.Lower pH values of weakly acidic refluxes as determinants of heartburn perception in gastroesophageal reflux disease patients with normal esophageal acid exposure[J].Dis Esophagus,2016,29(1):3-9.DOI:10.1111/dote.12284.
[11]Okumi H,Tashima K,Matsumoto K,et al.Dietary agonists of TRPV1 inhibit gastric acid secretion in mice[J].Planta Med,2012,78(17):1801-1806.DOI:10.1055/s-0032-1315387.
[12]Ericson A,Nur EM,Petersson F,et al.The effects of capsaicin on gastrin secretion in isolated human antral glands:before and after ingestion of red chilli[J].Dig Dis Sci,2009,54(3):491-498.DOI:10.1007/s10620-008-0400-1.
[13]M zsik G,Szolcs nyi J,R cz I.Gastroprotection induced by capsaicin in healthy human subjects[J].World Journal of Gastroenterology,2005,11(33):5180-5184.DOI:10.3748/wjg.v11.i33.5180.
[14]Sawamura S,Shirakawa H,Nakagawa T,et al.TRP Channels in the Brain:What Are They There For?[M].USA:CRC Press,2017:295-322.DOI:10.1201/9781315152837-17.
[15]Satyanarayana MN.Capsaicin and Gastric Ulcers[J].Crit Rev Food Sci Nutr,2006,46(4):275-328.DOI:10.1080/1040-830491379236.
[16]Yang D,Luo Z,Ma S,et al.Activation of TRPV1 by dietary capsaicin improves endothelium-dependent vasorelaxation and prevents hypertension[J].Cell Metabolism,2010,12(2):130-141.DOI:10.1016/j.cmet.2010.05.015.
[17]Raimura M,Tashima K,Matsumoto K,et al.Neuronal nitric oxide synthase-derived nitric oxide is involved in gastric mucosal hyperemic response to capsaicin in rats[J].Pharmacology,2013,92(1-2):60-70.DOI:10.1159/000351853.
[18]Kvietys PR.Physiology of the Gastrointestinal Microcirculation[J].PanVascular Medicine,2015:3501-3534.DOI:10.1007/978-3-642-37078-6_136.
[19]Silva RO,Bingana RD,Sales TMAL,et al.Role of TRPV1 receptor in inflammation and impairment of esophageal mucosal integrity in a murine model of nonerosive reflux disease[J].Neurogastroenterol Motil,2018,23:e13340.DOI:10.1126/science.aar3318.
[20]Carnevale V,Rohacs T.TRPV1:A Target for Rational Drug Design[J].Pharmaceuticals(Basel),2016,9:52.DOI:10.3390/ph9030052.
[21]Hofmann NA,Barth S,Waldeck-Weiermair M,et al.TRPV1 mediates cellular uptake of anandamide and thus promotes endothelial cell proliferation and network-formation[J].Biol Open,2014,3(12):1164-1172.DOI:10.1242/bio.20149571.
[22]Mastracci L,Spaggiari PF,Zentilin P,et al.Microscopic esophagitis in gastro-esophageal reflux disease:individual lesions,biopsy sampling,and clinical correlations[J].Virchows Arch,2009,454(1):31-39.DOI:10.1007/s00428-008-0704-8.
[23]Guarino MP,Cheng L,Ma J,et al.Increased TRPV1 gene expression in esophageal mucosa of patients with non-erosive and erosive reflux disease[J].Neurogastroenterol Motil,2010,22(7):746-751.DOI:10.1111/j.1365-2982.2010.01514.x.
[24]Matthews PJ,Aziz Q,Facer P,et al.Increased capsaicin receptor TR-PV1 nerve fibres in the inflamed human oesophagus[J].Eur J Gastroenterol Hepatol,2004,16(9):897-902.DOI:10.1097/00042737-200409000-00014.
[25]Banerjee B,Medda BK,Lazarova Z,et al.Effect of reflux-induced inflammation on transient receptor potential vanilloid one(TRPV1)expression inprimary sensory neurons innervating the oesophagus of rats[J].Neurogastroenterol Motil,2007,19(8):681-691.DOI:10.1111/j.1365-2982.2007.00947.x.
[26]Banerjee B,Medda BK,Schmidt J,et al.Altered expression of P2X3 in vagal and spinal afferents following esophagitis in rats[J].Histochem Cell Biol,2009,132(6):585-597.DOI:10.1007/s00418-009-0639-4.
[27]Ma J,Altomare A,Rieder F,et al.ATP:a mediator for HCl-induced TR-PV1 activation in esophageal mucosa[J].Am J Physiol Gastrointest Liver Physiol,2011,301:1075-1082.DOI:10.1152/ajpgi.00336.2011.
[28]Ma J,Altomare A,Guarino M,et al.HCl-induced and ATP-dependent upregulation of TRPV1 receptor expression and cytokine production by human esophageal epithelial cells[J].Am J Physiol Gastrointest Liver Physiol,2012,303:635-645.DOI:10.1152/ajpgi.00097.2012.
[29]Kim JJ,Kim N,Choi YJ,et al.Increased TRPV1 and PAR2 mRNA expression levels are associated only with the esophageal reflux symptoms,but not with the extraesophageal reflux symptoms[J].Medicine(Baltimore),2016,95(32):e4387.DOI:10.1097/MD.0000000000004387.
[30]Wu L,Oshima T,Shan J,et al.PAR-2 activation enhances weak acid-induced ATP release through TRPV1 and ASICs sensitization in human esophageal epithelial cells[J].Am J Physiol Gastrointest Liver Physiol,2015,309(8):695-702.DOI:10.1152/ajpgi.00162.2015.
[31]Matsumoto K,Hosoya T,Ishikawa E,et al.Distribution of transient receptor potential cation channel subfamily V member 1-expressing nerve fibers in mouse esophagus[J].Histochem Cell Biol,2014,142(6):635-644.DOI:10.1007/s00418-014-1246-6.
[32]Ward SM,Bayguinov J,Won KJ,et al.Distribution of the vanilloid receptor(VR1)in the gastrointestinal tract[J].J Comp Neurol,2003,465(1):121-135.DOI:10.1002/cne.10801.
[33]Kollarik M,Carr MJ,Ru F,et al.Transgene expression and effective gene silencing in vagal afferent neurons in vivo using recombinant adeno-associated virus vectors[J].J Physiol,2010,588:4303-4315.DOI:10.1113/jphysiol.2010.192971.
[34]Surdenikova L,Ru F,Nassenstein C,et al.The neural crest-and placodes-derived afferent innervation of the mouse esophagus[J].Neurogastroenterol Motil,2012,24(10):517-525.DOI:10.1007/s10620-017-4883-5.
[35]Matsumoto K,Hosoya T,Ishikawa E,et al.Distribution of transient receptor potential cation channel subfamily V member 1-expressing nerve fibers in mouse esophagus[J].Histochem Cell Biol,2014,142(6):635-644.DOI:10.1007/s00418-014-1246-6.
[36]Dusenkova S,Ru F,Surdenikova L,et al.The expression profile of acid-sensing ion channel(ASIC)subunits ASIC1a,ASIC1b,ASIC2a,ASIC2b,and ASIC3 in the esophageal vagal afferent nerve subtypes[J].Am J Physiol Gastrointest Liver Physiol,2014,307(9):922-930.DOI:10.1152/ajpgi.00129.2014.
[37]Ru F,Banovcin P Jr,Kollarik M.Acid sensitivity of the spinal dorsal root ganglia C-fiber nociceptors innervating the guinea pig esophagus[J].Neurogastroenterol Motil,2015,27(6):865-874.DOI:10.1111/nmo.12561.
[38]Yu X,Hu Y,Yu S.Effects of acid on vagal nociceptive afferent subtypes in guinea pig esophagus[J].Am J Physiol Gastrointest Liver Physiol,2014,307(4):471-478.DOI:10.1016/s0016-5085(14)60204-3.
[39]Holzer P.Transient receptor potential(TRP)channels as drug targets for diseases of the digestive system[J].Pharmacology&Therapeutics,2011,131(1):142-170.DOI:10.1016/j.pharmthera.2011.03.006.
[40]Patcharatrakul T,Gonlachanvit S.Chili Peppers,Curcumins,and Prebiotics in Gastrointestinal Health and Disease[J].Curr Gastroenterol Rep,2016,18(4):19.DOI:10.1007/s11894-016-0494-0.
[41]Krarup AL,Ny L,Astrand M,et al.Randomised clinical trial:the efficacy of a transient receptor potential vanilloid 1 antagonist AZD1386 in human oesophageal pain[J].Aliment Pharmacol Ther,2011,33:1113-1122.DOI:10.1111/j.1365-2036.2011.04629.x.
[42]Krarup AL,Ny L,Gunnarsson J,et al.Randomized clinical trial:inhibition of the TRPV1 system in patients with nonerosive gastroesophageal reflux disease and a partial response to PPI treatment is not associated with analgesia to esophageal experimental pain[J].Scand J Gastroenterol,2013,48:274-284.DOI:10.3109/00365521.2012.758769.
[2]Dhaliwal J.Epidemiology of gastro-oesophageal reflux disease:a systematic review[J].Gut,2014,63(6):710-717.DOI:10.1136/gut.2004.051821
[3]Ronkainen J,Aro P,Storskrubb T,et al.High prevalence of gastroesophageal reflux symptoms and esophagitis with or without symptoms in the general adult Swedish population:a Kalixanda study report[J].Scand J Gastroenterol,2005,40(3):275-285.DOI:10.1080/00365520510011579
[4]Kim N,Lee SW,Cho SI,et al.The prevalence of and risk factors for erosive oesophagitis and non-erosive reflux disease:a nationwide multicentre prospective study in Korea[J].Aliment Pharmacol Ther,2008,27(2):173-185.DOI:10.1111/j.1365-2036.2007.03561.x
[5]Horii T,Koike T,Abe Y,et al.Two distinct types of cancer of different origin may be mixed in gastroesophageal junction adenocarcinomas in Japan:Evidence from direct evaluation of gastric acid secretion[J].Scandinavian Journal of Gastroenterology,2011,46(6):710-719.DOI:10.3109/00365521.2011.565069
[6]王昭金,王延清.VR1受体在大鼠食管传入纤维的表达[J].解剖学报,2005,36(6):675-678.DOI:10.3321/j.issn:0529-1356.2005.06.022
[7]王凯,程鹏,王亚雷.TRPV1受体在胃食管反流病患者食管黏膜的表达及其与症状的关系[J].安徽医学,2012,33(2):140-143.DOI:10.3969/j.issn.1000-0399.2012.02.004.
[8]Guarino MPL,Cheng L,Ma J,et al.Increased TRPV1 gene expression in esophageal mucosa of patients with non-erosive and erosive reflux disease[J].Neurogastroenterol Motil,2010,22:746-751.DOI:10.1111/j.1365-2982.2010.01514.x.
[9]Savarino E,Tutuian R,Zentilin P,et al.Characteristics of reflux episodes and symptom association in patients with erosive esophagitis and nonerosive reflux disease:study using combined impedance-p H off therapy[J].Am J Gastroenterol,2009,105:1053-1061.DOI:10.1038/ajg.2009.670.
[10]de Bortoli N,Martinucci I,Savarino E,et al.Lower pH values of weakly acidic refluxes as determinants of heartburn perception in gastroesophageal reflux disease patients with normal esophageal acid exposure[J].Dis Esophagus,2016,29(1):3-9.DOI:10.1111/dote.12284.
[11]Okumi H,Tashima K,Matsumoto K,et al.Dietary agonists of TRPV1 inhibit gastric acid secretion in mice[J].Planta Med,2012,78(17):1801-1806.DOI:10.1055/s-0032-1315387.
[12]Ericson A,Nur EM,Petersson F,et al.The effects of capsaicin on gastrin secretion in isolated human antral glands:before and after ingestion of red chilli[J].Dig Dis Sci,2009,54(3):491-498.DOI:10.1007/s10620-008-0400-1.
[13]M zsik G,Szolcs nyi J,R cz I.Gastroprotection induced by capsaicin in healthy human subjects[J].World Journal of Gastroenterology,2005,11(33):5180-5184.DOI:10.3748/wjg.v11.i33.5180.
[14]Sawamura S,Shirakawa H,Nakagawa T,et al.TRP Channels in the Brain:What Are They There For?[M].USA:CRC Press,2017:295-322.DOI:10.1201/9781315152837-17.
[15]Satyanarayana MN.Capsaicin and Gastric Ulcers[J].Crit Rev Food Sci Nutr,2006,46(4):275-328.DOI:10.1080/1040-830491379236.
[16]Yang D,Luo Z,Ma S,et al.Activation of TRPV1 by dietary capsaicin improves endothelium-dependent vasorelaxation and prevents hypertension[J].Cell Metabolism,2010,12(2):130-141.DOI:10.1016/j.cmet.2010.05.015.
[17]Raimura M,Tashima K,Matsumoto K,et al.Neuronal nitric oxide synthase-derived nitric oxide is involved in gastric mucosal hyperemic response to capsaicin in rats[J].Pharmacology,2013,92(1-2):60-70.DOI:10.1159/000351853.
[18]Kvietys PR.Physiology of the Gastrointestinal Microcirculation[J].PanVascular Medicine,2015:3501-3534.DOI:10.1007/978-3-642-37078-6_136.
[19]Silva RO,Bingana RD,Sales TMAL,et al.Role of TRPV1 receptor in inflammation and impairment of esophageal mucosal integrity in a murine model of nonerosive reflux disease[J].Neurogastroenterol Motil,2018,23:e13340.DOI:10.1126/science.aar3318.
[20]Carnevale V,Rohacs T.TRPV1:A Target for Rational Drug Design[J].Pharmaceuticals(Basel),2016,9:52.DOI:10.3390/ph9030052.
[21]Hofmann NA,Barth S,Waldeck-Weiermair M,et al.TRPV1 mediates cellular uptake of anandamide and thus promotes endothelial cell proliferation and network-formation[J].Biol Open,2014,3(12):1164-1172.DOI:10.1242/bio.20149571.
[22]Mastracci L,Spaggiari PF,Zentilin P,et al.Microscopic esophagitis in gastro-esophageal reflux disease:individual lesions,biopsy sampling,and clinical correlations[J].Virchows Arch,2009,454(1):31-39.DOI:10.1007/s00428-008-0704-8.
[23]Guarino MP,Cheng L,Ma J,et al.Increased TRPV1 gene expression in esophageal mucosa of patients with non-erosive and erosive reflux disease[J].Neurogastroenterol Motil,2010,22(7):746-751.DOI:10.1111/j.1365-2982.2010.01514.x.
[24]Matthews PJ,Aziz Q,Facer P,et al.Increased capsaicin receptor TR-PV1 nerve fibres in the inflamed human oesophagus[J].Eur J Gastroenterol Hepatol,2004,16(9):897-902.DOI:10.1097/00042737-200409000-00014.
[25]Banerjee B,Medda BK,Lazarova Z,et al.Effect of reflux-induced inflammation on transient receptor potential vanilloid one(TRPV1)expression inprimary sensory neurons innervating the oesophagus of rats[J].Neurogastroenterol Motil,2007,19(8):681-691.DOI:10.1111/j.1365-2982.2007.00947.x.
[26]Banerjee B,Medda BK,Schmidt J,et al.Altered expression of P2X3 in vagal and spinal afferents following esophagitis in rats[J].Histochem Cell Biol,2009,132(6):585-597.DOI:10.1007/s00418-009-0639-4.
[27]Ma J,Altomare A,Rieder F,et al.ATP:a mediator for HCl-induced TR-PV1 activation in esophageal mucosa[J].Am J Physiol Gastrointest Liver Physiol,2011,301:1075-1082.DOI:10.1152/ajpgi.00336.2011.
[28]Ma J,Altomare A,Guarino M,et al.HCl-induced and ATP-dependent upregulation of TRPV1 receptor expression and cytokine production by human esophageal epithelial cells[J].Am J Physiol Gastrointest Liver Physiol,2012,303:635-645.DOI:10.1152/ajpgi.00097.2012.
[29]Kim JJ,Kim N,Choi YJ,et al.Increased TRPV1 and PAR2 mRNA expression levels are associated only with the esophageal reflux symptoms,but not with the extraesophageal reflux symptoms[J].Medicine(Baltimore),2016,95(32):e4387.DOI:10.1097/MD.0000000000004387.
[30]Wu L,Oshima T,Shan J,et al.PAR-2 activation enhances weak acid-induced ATP release through TRPV1 and ASICs sensitization in human esophageal epithelial cells[J].Am J Physiol Gastrointest Liver Physiol,2015,309(8):695-702.DOI:10.1152/ajpgi.00162.2015.
[31]Matsumoto K,Hosoya T,Ishikawa E,et al.Distribution of transient receptor potential cation channel subfamily V member 1-expressing nerve fibers in mouse esophagus[J].Histochem Cell Biol,2014,142(6):635-644.DOI:10.1007/s00418-014-1246-6.
[32]Ward SM,Bayguinov J,Won KJ,et al.Distribution of the vanilloid receptor(VR1)in the gastrointestinal tract[J].J Comp Neurol,2003,465(1):121-135.DOI:10.1002/cne.10801.
[33]Kollarik M,Carr MJ,Ru F,et al.Transgene expression and effective gene silencing in vagal afferent neurons in vivo using recombinant adeno-associated virus vectors[J].J Physiol,2010,588:4303-4315.DOI:10.1113/jphysiol.2010.192971.
[34]Surdenikova L,Ru F,Nassenstein C,et al.The neural crest-and placodes-derived afferent innervation of the mouse esophagus[J].Neurogastroenterol Motil,2012,24(10):517-525.DOI:10.1007/s10620-017-4883-5.
[35]Matsumoto K,Hosoya T,Ishikawa E,et al.Distribution of transient receptor potential cation channel subfamily V member 1-expressing nerve fibers in mouse esophagus[J].Histochem Cell Biol,2014,142(6):635-644.DOI:10.1007/s00418-014-1246-6.
[36]Dusenkova S,Ru F,Surdenikova L,et al.The expression profile of acid-sensing ion channel(ASIC)subunits ASIC1a,ASIC1b,ASIC2a,ASIC2b,and ASIC3 in the esophageal vagal afferent nerve subtypes[J].Am J Physiol Gastrointest Liver Physiol,2014,307(9):922-930.DOI:10.1152/ajpgi.00129.2014.
[37]Ru F,Banovcin P Jr,Kollarik M.Acid sensitivity of the spinal dorsal root ganglia C-fiber nociceptors innervating the guinea pig esophagus[J].Neurogastroenterol Motil,2015,27(6):865-874.DOI:10.1111/nmo.12561.
[38]Yu X,Hu Y,Yu S.Effects of acid on vagal nociceptive afferent subtypes in guinea pig esophagus[J].Am J Physiol Gastrointest Liver Physiol,2014,307(4):471-478.DOI:10.1016/s0016-5085(14)60204-3.
[39]Holzer P.Transient receptor potential(TRP)channels as drug targets for diseases of the digestive system[J].Pharmacology&Therapeutics,2011,131(1):142-170.DOI:10.1016/j.pharmthera.2011.03.006.
[40]Patcharatrakul T,Gonlachanvit S.Chili Peppers,Curcumins,and Prebiotics in Gastrointestinal Health and Disease[J].Curr Gastroenterol Rep,2016,18(4):19.DOI:10.1007/s11894-016-0494-0.
[41]Krarup AL,Ny L,Astrand M,et al.Randomised clinical trial:the efficacy of a transient receptor potential vanilloid 1 antagonist AZD1386 in human oesophageal pain[J].Aliment Pharmacol Ther,2011,33:1113-1122.DOI:10.1111/j.1365-2036.2011.04629.x.
[42]Krarup AL,Ny L,Gunnarsson J,et al.Randomized clinical trial:inhibition of the TRPV1 system in patients with nonerosive gastroesophageal reflux disease and a partial response to PPI treatment is not associated with analgesia to esophageal experimental pain[J].Scand J Gastroenterol,2013,48:274-284.DOI:10.3109/00365521.2012.758769.