• 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),將患者分為兩個組,A組為患慢性非活動性結(jié)石性膽囊炎者(n=10),B組為患慢性活動性膽囊炎者(n=25),在細胞凋亡早期胱門蛋白酶分裂的CK18用M30細胞凋亡酶聯(lián)免疫吸附測定,總細胞角蛋白18(從凋亡及壞死細胞中分離)用M65酶聯(lián)免疫吸附測定。然后計算M30/M65結(jié)果:胱門蛋白酶分裂的CK18,特別是總CK18在膽汁中的表達遠高于血清。在B組中,胱門蛋白酶分裂的CK18和總CK18的表達在膽囊組織和血清中表達差異相當(dāng)大。在膽囊粘膜上皮細胞胱門蛋白酶分裂的CK18染色呈強陽性。結(jié)論:CK18在膽囊上皮細胞中表達。胱門蛋白酶分裂的CK18和總CK18在膽囊組織中的表達遠高于血清中的表達。胱門蛋白酶分裂的CK18和總CK18的表達水平在活動性膽囊炎和非活動性膽囊炎中的表達并無明顯差異。

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

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.
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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.