• 1．南充市中心醫(yī)院普外三科, 四川南充 637000;2阿壩藏族羌族自治州黑水縣人民醫(yī)院外科,四川阿壩 623566;

目的:觀察和探討細(xì)胞角質(zhì)素CK18慢性膽囊炎患者的膽囊組織和血清中的表達(dá)及其意義。方法:35例經(jīng)腹腔鏡膽囊切除的慢性結(jié)石性膽囊炎患者(27例女性患者,8例男性患者,年齡在55.65±13.48歲),將患者分為兩個(gè)組,A組為患慢性非活動(dòng)性結(jié)石性膽囊炎者(n=10),B組為患慢性活動(dòng)性膽囊炎者(n=25),在細(xì)胞凋亡早期胱門蛋白酶分裂的CK18用M30細(xì)胞凋亡酶聯(lián)免疫吸附測(cè)定,總細(xì)胞角蛋白18(從凋亡及壞死細(xì)胞中分離)用M65酶聯(lián)免疫吸附測(cè)定。然后計(jì)算M30/M65結(jié)果:胱門蛋白酶分裂的CK18,特別是總CK18在膽汁中的表達(dá)遠(yuǎn)高于血清。在B組中,胱門蛋白酶分裂的CK18和總CK18的表達(dá)在膽囊組織和血清中表達(dá)差異相當(dāng)大。在膽囊粘膜上皮細(xì)胞胱門蛋白酶分裂的CK18染色呈強(qiáng)陽(yáng)性。結(jié)論:CK18在膽囊上皮細(xì)胞中表達(dá)。胱門蛋白酶分裂的CK18和總CK18在膽囊組織中的表達(dá)遠(yuǎn)高于血清中的表達(dá)。胱門蛋白酶分裂的CK18和總CK18的表達(dá)水平在活動(dòng)性膽囊炎和非活動(dòng)性膽囊炎中的表達(dá)并無(wú)明顯差異。

引用本文： 鄭小東,蘇拉木,東生. 細(xì)胞角質(zhì)蛋白18在慢性膽囊炎中的表達(dá)前瞻性研究. 華西醫(yī)學(xué), 2009, 24(9): 2258-2261. doi: 復(fù)制

版權(quán)信息： ?四川大學(xué)華西醫(yī)院華西期刊社《華西醫(yī)學(xué)》版權(quán)所有，未經(jīng)授權(quán)不得轉(zhuǎn)載、改編

1. MOLL R, FRANKE WW, SCHILLER DL, GEIGER B, KREPLER R. The catalogue of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells[J]. Cell, 1982,31(1):11-24.
2. CHOU CF, RIOPEL CL, ROTT LS, OMARY MB. A significant soluble keratin fraction in ’simple’ epithelial cells. Lack of an apparent phosphorylation and glycosylation role in keratin solubility[J].J Cell Sci, 1993, 105:433-444.
3. KU NO, LIAO J, OMARY MB. Apoptosis generates stable fragments of human type I keratins[J]. J Cell Biochem,1997,272:33197-33203.
4. CAULIN C, SALVESEN GS, OSHIMA RG. Caspase cleavage of keratin 18 and reorganization of intermediate filaments during epithelial cell apoptosis[J].J Cell Biol, 1997, 138:1379-1394.
5. KERR J. Shrinkage necrosis: a distinct mode of cellular death[J].J Pathol, 1971, 105:13-20.
6. KERR J, WYLLIE A, CURRIE A. Apoptosis: a basic biological phenomenon with wideranging implications in tissue kinetics[J].Br J Cancer, 1972, 26:239-257.
7. MAKIN G, HICKMAN J. Apoptosis and cancer chemotherapy[J].Cell Tissue Res, 2000, 301:143-152.
8. UENO T, TOI M, LINDER S. Detection of epithelial cell death in the body by cytokeratin 18 measurement[J].Biomedicine & Pharmacotherary, 2005, 59:S359-S362.
9. LINDER S, MANDIC HAVELKA A, UENO T, SHOSHAN MC. Determining tumor apoptosis and necrosis in patients serum using cytokeratin 18 as a biomarker[J].Cancer Letters, 2004, 214:1-9.
10. UENO T, TOI M, BIVEN K, BANDO H, OGAWA T, LINDER S. Measurement of an apoptotic product in the sera of breast cancer patients[J].Eur J Cancer, 2003, 39:769-774.
11. REED J. Dysregulation of apoptosis in cancer[J].J Clin Oncol, 1999,17:2941-2953.
12. WYLLIE AH. Apoptosis and carcinogenesis[J].Eur J Cell Biol, 1997,73:189-197.
13. BANTEL H, LUGERING A, HEIDEMANN J, et al.Detection of apoptosis caspase activation in sera from patients with chronic HCV infection is associated with fibrotic liver injury[J].Hepatology, 2004, 40:1078-1087.
14. MCPARTLAND JL, GUZAIL MA, KENDALL CH, PRINGLE JH. Apoptosis in chronic viral hepatitis parallels histological activity: an immunohistochemical investigation using antiactivated caspase3 and M30 cytodeath antibody[J]. Int J Exp Pathol,2005,86:19-24.
15. ROTH GA, KRENN C, BRUNNER M, et al.Elevated serum levels of epithelial cell apoptosisspecific cytokeratin 18 neoepitope m30 in critically ill patients[J]. Shock, 2004,22:218-220.
16. INUI A, SOGO T, KOMATSU H, MIYAKAWA H, FUJISAWA T. Antibobies againt cytokeratin 8/18 in a patient with de novo autoimmune hepatitis after livingdonor liver transplantation[J]. Liver Transpl, 2005, 11:504-507.
17. SELZNER M, RUDIGER H, SINDRAM D, SINDRAM D, MADDEN J, CLAVIEN PA. Mechanisms of ischemic injury are different in the steatotic and normal rat liver[J].Hepatology, 2000, 32:1280-1288.
18. LEERS MP, KOLGEN W, BJORKLUND V, et al.Immunocytochemical detection and mapping of cytokeratin18 neoepitope exposed during early apoptosis[J].J Pathol, 1999, 187:567-572.
19. BIVEN K, ERDAL H, HAGG M, et al.A novel assay for discovery and characterization of proapoptotic drugs for monitoring apoptosis[J].Apoptosis, 2003, 8(3):263-268.
20. HAGG M, BIVEN K, UENO T,〖WTBX〗et al.〖WTBZ〗 A novel highthroughput assay for screening of proapoptotic drugs[J]. Invest New Drugs,2002,20(3):253-259.
21. HETZ H, HOETZENECKER K, HACKER S, et al.Caspasecleaved cytokeratin 18 and 20 S proteasome in liver degeneration[J].J Clin Lab Anal,2007, 21:277-281.
22. YAGMUR E, TRAUTWEIN C, LEERS MP, et al.Elevated apoptosisassociated cytokeratin 18 fragments (CK18Asp386) in serum of patients with chronic liver diseases indicate hepatic and biliary inflammation[J].Clin Biochem,2007, 40(910):651-655.
23. YILMAZ Y, DOLAR E, ULUKAYA E, et al.Soluble forms of extracellular cytokeratin 18 may differentiate simple steatosis from nonalcoholic steatohepatitis[J]. World J Gastroenterol, 2007,13(6):837-844.
24. YANAGISAWA N, MIKAMI T, KOIKE M, OKAYASU I. Enhanced cell kinetics, p53 accumulation and high p21WAF1 expression in chronic cholecystitis: comparison with background mucosa of gallbladder carcinomas[J]. Histopathology, 2000, 36:54-61.
25. XIONG Y, HANNON GJ, ZHANG H, CASSO D, KOBAYASHI R, BEACH D. p21 is a universal inhibitor of cyclin kinases[J]. Nature, 1993, 366:701-707.
  1. 1. MOLL R, FRANKE WW, SCHILLER DL, GEIGER B, KREPLER R. The catalogue of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells[J]. Cell, 1982,31(1):11-24.
  2. 2. CHOU CF, RIOPEL CL, ROTT LS, OMARY MB. A significant soluble keratin fraction in ’simple’ epithelial cells. Lack of an apparent phosphorylation and glycosylation role in keratin solubility[J].J Cell Sci, 1993, 105:433-444.
  3. 3. KU NO, LIAO J, OMARY MB. Apoptosis generates stable fragments of human type I keratins[J]. J Cell Biochem,1997,272:33197-33203.
  4. 4. CAULIN C, SALVESEN GS, OSHIMA RG. Caspase cleavage of keratin 18 and reorganization of intermediate filaments during epithelial cell apoptosis[J].J Cell Biol, 1997, 138:1379-1394.
  5. 5. KERR J. Shrinkage necrosis: a distinct mode of cellular death[J].J Pathol, 1971, 105:13-20.
  6. 6. KERR J, WYLLIE A, CURRIE A. Apoptosis: a basic biological phenomenon with wideranging implications in tissue kinetics[J].Br J Cancer, 1972, 26:239-257.
  7. 7. MAKIN G, HICKMAN J. Apoptosis and cancer chemotherapy[J].Cell Tissue Res, 2000, 301:143-152.
  8. 8. UENO T, TOI M, LINDER S. Detection of epithelial cell death in the body by cytokeratin 18 measurement[J].Biomedicine & Pharmacotherary, 2005, 59:S359-S362.
  9. 9. LINDER S, MANDIC HAVELKA A, UENO T, SHOSHAN MC. Determining tumor apoptosis and necrosis in patients serum using cytokeratin 18 as a biomarker[J].Cancer Letters, 2004, 214:1-9.
  10. 10. UENO T, TOI M, BIVEN K, BANDO H, OGAWA T, LINDER S. Measurement of an apoptotic product in the sera of breast cancer patients[J].Eur J Cancer, 2003, 39:769-774.
  11. 11. REED J. Dysregulation of apoptosis in cancer[J].J Clin Oncol, 1999,17:2941-2953.
  12. 12. WYLLIE AH. Apoptosis and carcinogenesis[J].Eur J Cell Biol, 1997,73:189-197.
  13. 13. BANTEL H, LUGERING A, HEIDEMANN J, et al.Detection of apoptosis caspase activation in sera from patients with chronic HCV infection is associated with fibrotic liver injury[J].Hepatology, 2004, 40:1078-1087.
  14. 14. MCPARTLAND JL, GUZAIL MA, KENDALL CH, PRINGLE JH. Apoptosis in chronic viral hepatitis parallels histological activity: an immunohistochemical investigation using antiactivated caspase3 and M30 cytodeath antibody[J]. Int J Exp Pathol,2005,86:19-24.
  15. 15. ROTH GA, KRENN C, BRUNNER M, et al.Elevated serum levels of epithelial cell apoptosisspecific cytokeratin 18 neoepitope m30 in critically ill patients[J]. Shock, 2004,22:218-220.
  16. 16. INUI A, SOGO T, KOMATSU H, MIYAKAWA H, FUJISAWA T. Antibobies againt cytokeratin 8/18 in a patient with de novo autoimmune hepatitis after livingdonor liver transplantation[J]. Liver Transpl, 2005, 11:504-507.
  17. 17. SELZNER M, RUDIGER H, SINDRAM D, SINDRAM D, MADDEN J, CLAVIEN PA. Mechanisms of ischemic injury are different in the steatotic and normal rat liver[J].Hepatology, 2000, 32:1280-1288.
  18. 18. LEERS MP, KOLGEN W, BJORKLUND V, et al.Immunocytochemical detection and mapping of cytokeratin18 neoepitope exposed during early apoptosis[J].J Pathol, 1999, 187:567-572.
  19. 19. BIVEN K, ERDAL H, HAGG M, et al.A novel assay for discovery and characterization of proapoptotic drugs for monitoring apoptosis[J].Apoptosis, 2003, 8(3):263-268.
  20. 20. HAGG M, BIVEN K, UENO T,〖WTBX〗et al.〖WTBZ〗 A novel highthroughput assay for screening of proapoptotic drugs[J]. Invest New Drugs,2002,20(3):253-259.
  21. 21. HETZ H, HOETZENECKER K, HACKER S, et al.Caspasecleaved cytokeratin 18 and 20 S proteasome in liver degeneration[J].J Clin Lab Anal,2007, 21:277-281.
  22. 22. YAGMUR E, TRAUTWEIN C, LEERS MP, et al.Elevated apoptosisassociated cytokeratin 18 fragments (CK18Asp386) in serum of patients with chronic liver diseases indicate hepatic and biliary inflammation[J].Clin Biochem,2007, 40(910):651-655.
  23. 23. YILMAZ Y, DOLAR E, ULUKAYA E, et al.Soluble forms of extracellular cytokeratin 18 may differentiate simple steatosis from nonalcoholic steatohepatitis[J]. World J Gastroenterol, 2007,13(6):837-844.
  24. 24. YANAGISAWA N, MIKAMI T, KOIKE M, OKAYASU I. Enhanced cell kinetics, p53 accumulation and high p21WAF1 expression in chronic cholecystitis: comparison with background mucosa of gallbladder carcinomas[J]. Histopathology, 2000, 36:54-61.
  25. 25. XIONG Y, HANNON GJ, ZHANG H, CASSO D, KOBAYASHI R, BEACH D. p21 is a universal inhibitor of cyclin kinases[J]. Nature, 1993, 366:701-707.