慢性胰腺炎发生的分子机制
|
摘要
<正>慢性胰腺炎(chronic pancreatitis,CP)是饮酒、自身免疫、遗传因素等多种原因所致的胰腺实质内腺泡和小管的反复或持续性损伤,引起腺泡和胰岛细胞萎缩或消失,最终被纤维化组织替代,引起不同程度的胰腺内/外分泌功能障碍,是胰腺的一种进行性炎性疾病~([1]);临床上患者表现为持续性或反复发作性腹痛、食欲减退和脂肪泻等,严重影响患者生
引文
[1]Sakurai T,Kudo M,Fukuta N,et al.Involvement of angiotensin Ⅱ and reactive oxygen species in pancreatic fibrosis[J].Pancreatology,2011,11(Suppl 2):7-13.
[2]Yadav D,Lowenfels A B.The epidemiology of pancreatitis and pancreatic cancer[J].Gastroenterology,2013,144(6):1252-1261.
[3]Wang L W,Li Z S,Li S D,et al.Prevalence and clinical features of chronic pancreatitis in China:a retrospective multicenter analysis over 10 years[J].Pancreas,2009,38(3):248-254.
[4]Omary M B,Lugea A,Lowe A W,et al.The pancreatic stellate cell:a star on the rise in pancreatic diseases[J].J Clin Invest,2007,117(1):50-59.
[5]Bynigeri R R,Jakkampudi A,Jangala R,et al.Pancreatic stellate cell:Pandora’s box for pancreatic disease biology[J].World J Gastroenterol,2017,23(3):382-405.
[6]Apte M,Pirola R,Wilson J.The fibrosis of chronic pancreatitis:new insights into the role of pancreatic stellate cells[J].Antioxid Redox Signal,2011,15(10):2711-2722.
[7]Erkan M,Adler G,Apte M V,et al.Stella TUM:current consensus and discussion on pancreatic stellate cell research[J].Gut,2012,61(2):172-178.
[8]Andoh A,Takaya H,Saotome T,et al.Cytokine regulation of chemokine(IL-8,MCP-1,and RANTES)gene expression in human pancreatic periacinar myofibroblasts[J].Gastroenterology,2000,119(1):211-219.
[9]Ulmasov B,Neuschwander-Tetri B A,Lai J,et al.Inhibitors of Arg-Gly-Asp-Binding integrins reduce development of pancreatic fibrosis in mice[J].Cell Mol Gastroenterol Hepatol,2016,2(4):499-518.
[10]Shimizu K.Pancreatic stellate cells:molecular mechanism of pancreatic fibrosis[J].J Gastroenterol Hepatol,2008,23(Suppl 1):S119-S121.
[11]王兴鹏,龚自华.胰腺星状细胞在大鼠胰腺纤维化形成中的作用[J].中华消化杂志,2003,23(8):14-17.
[12]Tahara H,Sato K,Yamazaki Y,et al.Transforming growth factor-αactivates pancreatic stellate cells and may be involved in matrix metalloproteinase-1 upregulation[J].Lab Invest,2013,93(6):720-732.
[13]Qian Z Y,Peng Q,Zhang Z W,et al.Roles of Smad3and Smad7 in rat pancreatic stellate cells activated by transforming growth factor-beta 1[J].Hepatobiliary Pancreat Dis Int,2010,9(5):531-536.
[14]Yoo B M,Yeo M,Oh T Y,et al.Amelioration of pancreatic fibrosis in mice with defective TGF-beta signaling[J].Pancreas,2005,30(3):e71-e79.
[15]Aoki H,Ohnishi H,Hama K,et al.Autocrine loop between TGF-beta1 and IL-1beta through Smad3-and ERK-dependent pathways in rat pancreatic stellate cells[J].Am J Physiol Cell Physiol,2006,290(4):C1100-C1108.
[16]Aoki H,Ohnishi H,Hama K,et al.Existence of autocrine loop between interleukin-6 and transforming growth factor-beta1 in activated rat pancreatic stellate cells[J].J Cell Biochem,2006,99(1):221-228.
[17]Shek F W,Benyon R C,Walker F M,et al.Expression of transforming growth factor-beta 1 by pancreatic stellate cells and its implications for matrix secretion and turnover in chronic pancreatitis[J].Am J Pathol,2002,160(5):1787-1798.
[18]张青,王亚丽,卢美丽,等.TGFβ1刺激不同时间对胰腺腺泡细胞中ZNF580和EMT相关因子的影响[J].武警后勤学院学报(医学版),2016,25(12):959-963.
[19]Liu H,Yu K,Ma P,et al.Long noncoding RNA myocardial infarction-associated transcript regulated the pancreatic stellate cell activation to promote the fibrosis process of chronic pancreatitis[J].J Cell Biochem,2018.
[20]苏丽婷,夏时海,郑永青.转化生长因子β1Ⅱ型受体在大鼠慢性胰腺炎中的表达及氧化苦参碱对其的影响[J].世界华人消化杂志,2011,19(2):121-125.
[21]王昱良,郑永青,夏时海,等.氧化苦参碱对慢性胰腺炎胰腺组织中Ⅰ型胶原及α-SMA的影响[J].世界华人消化杂志,2010,18(13):1331-1336.
[22]宗林飞.基于JAK2/STAT3通路的氧化苦参碱抗胰腺纤维化机制研究.见:夏时海,向晓辉,主编..
[23]李嫚华,陈凯,张青,等.氧化苦参碱通过促进胰腺星状细胞株中Gli2表达发挥抗胰腺纤维化作用[J].中草药,2018,49(13):3069-3073.
[24]张斌,许威,李如月,等.氧化苦参碱抑制DBTC刺激的胰腺腺泡细胞中上皮间质转化相关蛋白及TβRⅡ和p-Smad2/3表达[J].遵义医学院学报,2017,40(5):531-535.
[25]Tsang S W,Zhang H,Lin C,et al.Rhein,a natural anthraquinone derivative,attenuates the activation of pancreatic stellate cells and ameliorates pancreatic fibrosis in mice with experimental chronic pancreatitis[J].PLo S One,2013,8(12):e82201.
[26]Liu L,Zhu Y,Nu M,et al.Neuronal transforming growth factor beta signaling via SMAD3 contributes to pain in animal models of chronic pancreatitis[J].Gastroenterology,2018,154(8):2252-2265.e2.
[27]田珍珍,朱杰,王淑华,等.慢性胰腺炎患者胰腺和血清中TLR4信号通路关键因子的检测及其意义[J].吉林大学学报(医学版),2013,39(4):763-767,866.
[28]Szabo G,Mandrekar P,Oak S,et al.Effect of ethanol on inflammatory responses.Implications for pancreatitis[J].Pancreatology,2007,7(2-3):115-123.
[29]Vonlaufen A,Phillips P A,Xu Z,et al.Withdrawal of alcohol promotes regression while continued alcohol intake promotes persistence of LPS-induced pancreatic injury in alcohol-fed rats[J].Gut,2011,60(2):238-246.
[30]Pan L F,Yu L,Wang L M,et al.The toll-like receptor4 antagonist transforming growth factor-β-activated kinase(TAK)-242 attenuates taurocholate-induced oxidative stress through regulating mitochondrial function in mice pancreatic acinar cells[J].J Surg Res,2016,206(2):298-306.
[31]Pan L F,Yu L,Wang L M,et al.The Toll-like receptor 4 antagonist TAK-242 protects against chronic pancreatitis in rats[J].Mol Med Rep,2017,16(4):3863-3868.
[32]李如月,向晓辉,张斌,等.氧化苦参碱通过胰腺星状细胞中miRNA-211-5p调节TLR4/NF-κB通路调控炎性反应[J].药物评价研究,2018,41(4):540-546.
[33]卢美丽,陈凯,张青,等.氧化苦参碱对脂多糖诱导的AR42J细胞MyD88/NF-κBp65信号通路的调节作用[J].武警后勤学院学报(医学版),2017,26(8):645-648.
[34]Lu M,Zhang Q,Chen K,et al.The regulatory effect of oxymatrine on the TLR4/MyD88/NF-κB signaling pathway in lipopolysaccharide-induced MS1 cells[J].Phytomedicine,2017,36:153-159.
[35]Wang Y S,Li Y Y,Wang L H,et al.Tanshinone IIAattenuates chronic pancreatitis-induced pain in rats via downregulation of HMGB1 and TRL4 expression in the spinal cord[J].Pain Physician,2015,18(4):E615-E628.
[36]Komar H M,Serpa G,Kerscher C,et al.Inhibition of Jak/STAT signaling reduces the activation of pancreatic stellate cells in vitro and limits caerulein-induced chronic pancreatitis in vivo[J].Sci Rep,2017,7(1):1787.
[37]张青,李嫚华,陈凯,等.Gli1基因沉默通过抑制JAK2/STAT3信号通路阻抑TGF-β1诱导胰腺星状细胞纤维化[J].武警后勤学院学报(医学版),2017,26(12):1028-1033.
[38]朱林佳.大柴胡汤通过调控IL-6/STAT3信号通路对L-Arginine诱发CP胰腺纤维化的防治作用[D].西安:陕西中医药大学,2016.
[39]Gukovsky I,Gukovskaya A S.Impaired autophagy triggers chronic pancreatitis:lessons from pancreas-specific atg5 knockout mice[J].Gastroenterology,2015,148(3):501-505.
[40]Diakopoulos K N,Lesina M,W9rmann S,et al.Impaired autophagy induces chronic atrophic pancreatitis in mice via sex-and nutrition-dependent processes[J].Gastroenterology,2015,148(3):626-638.e17.
[41]Antonucci L,Fagman J B,Kim J Y,et al.Basal autophagy maintains pancreatic acinar cell homeostasis and protein synthesis and prevents ER stress[J].Proc Natl Acad Sci U S A,2015,112(45):E6166-E6174.
[42]Li N,Wu X,Holzer R G,et al.Loss of acinar cell IKKαtriggers spontaneous pancreatitis in mice[J].JClin Invest,2013,123(5):2231-2243.
[43]Mareninova O A,Sendler M,Malla S R,et al.Lysosome associated membrane proteins maintain pancreatic acinar cell homeostasis:LAMP-2 deficient mice develop pancreatitis[J].Cell Mol Gastroenterol Hepatol,2015,1(6):678-694.
[44]Li C X,Cui L H,Zhuo Y Z,et al.Inhibiting autophagy promotes collagen degradation by regulating matrix metalloproteinases in pancreatic stellate cells[J].Life Sci,2018,208:276-283.
[45]Xu M,Wang G,Zhou H,et al.TGF-β1-miR-200aPTEN induces epithelial-mesenchymal transition and fibrosis of pancreatic stellate cells[J].Mol Cell Biochem,2017,431(1-2):161-168.
[46]Li L,Wang G,Hu J S,et al.RB1CC1-enhanced autophagy facilitates PSCs activation and pancreatic fibrogenesis in chronic pancreatitis[J].Cell Death Dis,2018,9(10):952.
[47]Cui L,Li C,Gao G,et al.FTY720 inhibits the activation of pancreatic stellate cells by promoting apoptosis and suppressing autophagy via the AMPK/mTOR pathway[J].Life Sci,2019,217:243-250.
[48]Cui L H,Li C X,Zhuo Y Z,et al.Saikosaponin d ameliorates pancreatic fibrosis by inhibiting autophagy of pancreatic stellate cells via PI3K/Akt/mTOR pathway[J].Chem Biol Interact,2019,300:18-26.
[49]Xue R,Wang J,Yang L,et al.Coenzyme Q10 ameliorates pancreatic fibrosis via the ROS-Triggered mTORsignaling pathway[J].Oxid Med Cell Longev,2019,2019:8039694.
[50]Xue R,Yang J,Wu J,et al.Coenzyme Q10 inhibits the activation of pancreatic stellate cells through PI3K/AKT/mTOR signaling pathway[J].Oncotarget,2017,8(54):92300-92311.
[51]Berna M J,Seiz O,Nast J F,et al.CCK1 and CCK2receptors are expressed on pancreatic stellate cells and induce collagen production[J].J Biol Chem,2010,285(50):38905-38914.
[52]Tsang S W,Zhang H J,Chen Y G,et al.Eruberin A,a natural flavanol glycoside,exerts anti-fibrotic action on pancreatic stellate cells[J].Cell Physiol Biochem,2015,36(6):2433-2446.
[53]Boulling A,Masson E,Zou W B,et al.Identification of a functional enhancer variant within the chronic pancreatitis-associated SPINK1 c.101A>G(p.Asn34Ser)-containing haplotype[J].Hum Mutat,2017,38(8):1014-1024.
[54]Qian Y Y,Zou W B,Chen J M,et al.Identification of a novel SPINK1 deletion in a teenager with idiopathic chronic pancreatitis[J].Dig Liver Dis,2017,49(8):941-943.
[55]Wang D,Xin L,Lin J H,et al.Identifying miRNA-mRNA regulation network of chronic pancreatitis based on the significant functional expression[J].Medicine(Baltimore),2017,96(21):e6668.
[56]Hegyi E,Sahin-Tóth M.Genetic risk in chronic pancreatitis:The trypsin-dependent pathway[J].Dig Dis Sci,2017,62(7):1692-1701.
[57]Weiss F U,Skube M E,Lerch M M.Chronic pancreatitis:an update on genetic risk factors[J].Curr Opin Gastroenterol,2018,34(5):322-329.
[2]Yadav D,Lowenfels A B.The epidemiology of pancreatitis and pancreatic cancer[J].Gastroenterology,2013,144(6):1252-1261.
[3]Wang L W,Li Z S,Li S D,et al.Prevalence and clinical features of chronic pancreatitis in China:a retrospective multicenter analysis over 10 years[J].Pancreas,2009,38(3):248-254.
[4]Omary M B,Lugea A,Lowe A W,et al.The pancreatic stellate cell:a star on the rise in pancreatic diseases[J].J Clin Invest,2007,117(1):50-59.
[5]Bynigeri R R,Jakkampudi A,Jangala R,et al.Pancreatic stellate cell:Pandora’s box for pancreatic disease biology[J].World J Gastroenterol,2017,23(3):382-405.
[6]Apte M,Pirola R,Wilson J.The fibrosis of chronic pancreatitis:new insights into the role of pancreatic stellate cells[J].Antioxid Redox Signal,2011,15(10):2711-2722.
[7]Erkan M,Adler G,Apte M V,et al.Stella TUM:current consensus and discussion on pancreatic stellate cell research[J].Gut,2012,61(2):172-178.
[8]Andoh A,Takaya H,Saotome T,et al.Cytokine regulation of chemokine(IL-8,MCP-1,and RANTES)gene expression in human pancreatic periacinar myofibroblasts[J].Gastroenterology,2000,119(1):211-219.
[9]Ulmasov B,Neuschwander-Tetri B A,Lai J,et al.Inhibitors of Arg-Gly-Asp-Binding integrins reduce development of pancreatic fibrosis in mice[J].Cell Mol Gastroenterol Hepatol,2016,2(4):499-518.
[10]Shimizu K.Pancreatic stellate cells:molecular mechanism of pancreatic fibrosis[J].J Gastroenterol Hepatol,2008,23(Suppl 1):S119-S121.
[11]王兴鹏,龚自华.胰腺星状细胞在大鼠胰腺纤维化形成中的作用[J].中华消化杂志,2003,23(8):14-17.
[12]Tahara H,Sato K,Yamazaki Y,et al.Transforming growth factor-αactivates pancreatic stellate cells and may be involved in matrix metalloproteinase-1 upregulation[J].Lab Invest,2013,93(6):720-732.
[13]Qian Z Y,Peng Q,Zhang Z W,et al.Roles of Smad3and Smad7 in rat pancreatic stellate cells activated by transforming growth factor-beta 1[J].Hepatobiliary Pancreat Dis Int,2010,9(5):531-536.
[14]Yoo B M,Yeo M,Oh T Y,et al.Amelioration of pancreatic fibrosis in mice with defective TGF-beta signaling[J].Pancreas,2005,30(3):e71-e79.
[15]Aoki H,Ohnishi H,Hama K,et al.Autocrine loop between TGF-beta1 and IL-1beta through Smad3-and ERK-dependent pathways in rat pancreatic stellate cells[J].Am J Physiol Cell Physiol,2006,290(4):C1100-C1108.
[16]Aoki H,Ohnishi H,Hama K,et al.Existence of autocrine loop between interleukin-6 and transforming growth factor-beta1 in activated rat pancreatic stellate cells[J].J Cell Biochem,2006,99(1):221-228.
[17]Shek F W,Benyon R C,Walker F M,et al.Expression of transforming growth factor-beta 1 by pancreatic stellate cells and its implications for matrix secretion and turnover in chronic pancreatitis[J].Am J Pathol,2002,160(5):1787-1798.
[18]张青,王亚丽,卢美丽,等.TGFβ1刺激不同时间对胰腺腺泡细胞中ZNF580和EMT相关因子的影响[J].武警后勤学院学报(医学版),2016,25(12):959-963.
[19]Liu H,Yu K,Ma P,et al.Long noncoding RNA myocardial infarction-associated transcript regulated the pancreatic stellate cell activation to promote the fibrosis process of chronic pancreatitis[J].J Cell Biochem,2018.
[20]苏丽婷,夏时海,郑永青.转化生长因子β1Ⅱ型受体在大鼠慢性胰腺炎中的表达及氧化苦参碱对其的影响[J].世界华人消化杂志,2011,19(2):121-125.
[21]王昱良,郑永青,夏时海,等.氧化苦参碱对慢性胰腺炎胰腺组织中Ⅰ型胶原及α-SMA的影响[J].世界华人消化杂志,2010,18(13):1331-1336.
[22]宗林飞.基于JAK2/STAT3通路的氧化苦参碱抗胰腺纤维化机制研究.见:夏时海,向晓辉,主编..
[23]李嫚华,陈凯,张青,等.氧化苦参碱通过促进胰腺星状细胞株中Gli2表达发挥抗胰腺纤维化作用[J].中草药,2018,49(13):3069-3073.
[24]张斌,许威,李如月,等.氧化苦参碱抑制DBTC刺激的胰腺腺泡细胞中上皮间质转化相关蛋白及TβRⅡ和p-Smad2/3表达[J].遵义医学院学报,2017,40(5):531-535.
[25]Tsang S W,Zhang H,Lin C,et al.Rhein,a natural anthraquinone derivative,attenuates the activation of pancreatic stellate cells and ameliorates pancreatic fibrosis in mice with experimental chronic pancreatitis[J].PLo S One,2013,8(12):e82201.
[26]Liu L,Zhu Y,Nu M,et al.Neuronal transforming growth factor beta signaling via SMAD3 contributes to pain in animal models of chronic pancreatitis[J].Gastroenterology,2018,154(8):2252-2265.e2.
[27]田珍珍,朱杰,王淑华,等.慢性胰腺炎患者胰腺和血清中TLR4信号通路关键因子的检测及其意义[J].吉林大学学报(医学版),2013,39(4):763-767,866.
[28]Szabo G,Mandrekar P,Oak S,et al.Effect of ethanol on inflammatory responses.Implications for pancreatitis[J].Pancreatology,2007,7(2-3):115-123.
[29]Vonlaufen A,Phillips P A,Xu Z,et al.Withdrawal of alcohol promotes regression while continued alcohol intake promotes persistence of LPS-induced pancreatic injury in alcohol-fed rats[J].Gut,2011,60(2):238-246.
[30]Pan L F,Yu L,Wang L M,et al.The toll-like receptor4 antagonist transforming growth factor-β-activated kinase(TAK)-242 attenuates taurocholate-induced oxidative stress through regulating mitochondrial function in mice pancreatic acinar cells[J].J Surg Res,2016,206(2):298-306.
[31]Pan L F,Yu L,Wang L M,et al.The Toll-like receptor 4 antagonist TAK-242 protects against chronic pancreatitis in rats[J].Mol Med Rep,2017,16(4):3863-3868.
[32]李如月,向晓辉,张斌,等.氧化苦参碱通过胰腺星状细胞中miRNA-211-5p调节TLR4/NF-κB通路调控炎性反应[J].药物评价研究,2018,41(4):540-546.
[33]卢美丽,陈凯,张青,等.氧化苦参碱对脂多糖诱导的AR42J细胞MyD88/NF-κBp65信号通路的调节作用[J].武警后勤学院学报(医学版),2017,26(8):645-648.
[34]Lu M,Zhang Q,Chen K,et al.The regulatory effect of oxymatrine on the TLR4/MyD88/NF-κB signaling pathway in lipopolysaccharide-induced MS1 cells[J].Phytomedicine,2017,36:153-159.
[35]Wang Y S,Li Y Y,Wang L H,et al.Tanshinone IIAattenuates chronic pancreatitis-induced pain in rats via downregulation of HMGB1 and TRL4 expression in the spinal cord[J].Pain Physician,2015,18(4):E615-E628.
[36]Komar H M,Serpa G,Kerscher C,et al.Inhibition of Jak/STAT signaling reduces the activation of pancreatic stellate cells in vitro and limits caerulein-induced chronic pancreatitis in vivo[J].Sci Rep,2017,7(1):1787.
[37]张青,李嫚华,陈凯,等.Gli1基因沉默通过抑制JAK2/STAT3信号通路阻抑TGF-β1诱导胰腺星状细胞纤维化[J].武警后勤学院学报(医学版),2017,26(12):1028-1033.
[38]朱林佳.大柴胡汤通过调控IL-6/STAT3信号通路对L-Arginine诱发CP胰腺纤维化的防治作用[D].西安:陕西中医药大学,2016.
[39]Gukovsky I,Gukovskaya A S.Impaired autophagy triggers chronic pancreatitis:lessons from pancreas-specific atg5 knockout mice[J].Gastroenterology,2015,148(3):501-505.
[40]Diakopoulos K N,Lesina M,W9rmann S,et al.Impaired autophagy induces chronic atrophic pancreatitis in mice via sex-and nutrition-dependent processes[J].Gastroenterology,2015,148(3):626-638.e17.
[41]Antonucci L,Fagman J B,Kim J Y,et al.Basal autophagy maintains pancreatic acinar cell homeostasis and protein synthesis and prevents ER stress[J].Proc Natl Acad Sci U S A,2015,112(45):E6166-E6174.
[42]Li N,Wu X,Holzer R G,et al.Loss of acinar cell IKKαtriggers spontaneous pancreatitis in mice[J].JClin Invest,2013,123(5):2231-2243.
[43]Mareninova O A,Sendler M,Malla S R,et al.Lysosome associated membrane proteins maintain pancreatic acinar cell homeostasis:LAMP-2 deficient mice develop pancreatitis[J].Cell Mol Gastroenterol Hepatol,2015,1(6):678-694.
[44]Li C X,Cui L H,Zhuo Y Z,et al.Inhibiting autophagy promotes collagen degradation by regulating matrix metalloproteinases in pancreatic stellate cells[J].Life Sci,2018,208:276-283.
[45]Xu M,Wang G,Zhou H,et al.TGF-β1-miR-200aPTEN induces epithelial-mesenchymal transition and fibrosis of pancreatic stellate cells[J].Mol Cell Biochem,2017,431(1-2):161-168.
[46]Li L,Wang G,Hu J S,et al.RB1CC1-enhanced autophagy facilitates PSCs activation and pancreatic fibrogenesis in chronic pancreatitis[J].Cell Death Dis,2018,9(10):952.
[47]Cui L,Li C,Gao G,et al.FTY720 inhibits the activation of pancreatic stellate cells by promoting apoptosis and suppressing autophagy via the AMPK/mTOR pathway[J].Life Sci,2019,217:243-250.
[48]Cui L H,Li C X,Zhuo Y Z,et al.Saikosaponin d ameliorates pancreatic fibrosis by inhibiting autophagy of pancreatic stellate cells via PI3K/Akt/mTOR pathway[J].Chem Biol Interact,2019,300:18-26.
[49]Xue R,Wang J,Yang L,et al.Coenzyme Q10 ameliorates pancreatic fibrosis via the ROS-Triggered mTORsignaling pathway[J].Oxid Med Cell Longev,2019,2019:8039694.
[50]Xue R,Yang J,Wu J,et al.Coenzyme Q10 inhibits the activation of pancreatic stellate cells through PI3K/AKT/mTOR signaling pathway[J].Oncotarget,2017,8(54):92300-92311.
[51]Berna M J,Seiz O,Nast J F,et al.CCK1 and CCK2receptors are expressed on pancreatic stellate cells and induce collagen production[J].J Biol Chem,2010,285(50):38905-38914.
[52]Tsang S W,Zhang H J,Chen Y G,et al.Eruberin A,a natural flavanol glycoside,exerts anti-fibrotic action on pancreatic stellate cells[J].Cell Physiol Biochem,2015,36(6):2433-2446.
[53]Boulling A,Masson E,Zou W B,et al.Identification of a functional enhancer variant within the chronic pancreatitis-associated SPINK1 c.101A>G(p.Asn34Ser)-containing haplotype[J].Hum Mutat,2017,38(8):1014-1024.
[54]Qian Y Y,Zou W B,Chen J M,et al.Identification of a novel SPINK1 deletion in a teenager with idiopathic chronic pancreatitis[J].Dig Liver Dis,2017,49(8):941-943.
[55]Wang D,Xin L,Lin J H,et al.Identifying miRNA-mRNA regulation network of chronic pancreatitis based on the significant functional expression[J].Medicine(Baltimore),2017,96(21):e6668.
[56]Hegyi E,Sahin-Tóth M.Genetic risk in chronic pancreatitis:The trypsin-dependent pathway[J].Dig Dis Sci,2017,62(7):1692-1701.
[57]Weiss F U,Skube M E,Lerch M M.Chronic pancreatitis:an update on genetic risk factors[J].Curr Opin Gastroenterol,2018,34(5):322-329.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |