Helicobacter pylori và Axit Acetylsalicylic Tăng Cường Quá Trình Apoptosis Qua Đường Phân Tử Fas Trong Các Tế Bào Biểu Mô Dạ Dày Của Thỏ

Digestive Diseases and Sciences - Tập 47 - Trang 809-817 - 2002
Kazuhiro Watanabe1, Satoshi Hoshiya1, Kengo Tokunaga1, Akifumi Tanaka1, Hidehiro Watanabe2, Shinya Nagamatsu3, Hitoshi Ishida1, Shin'ichi Takahashi1
1Third Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan
2The First Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan
3Biochemistry II, Kyorin University School of Medicine, Tokyo, Japan

Tóm tắt

Cơ chế gây ra sự apoptosis tế bào biểu mô dạ dày do cả H. pylori và NSAIDs vẫn chưa được làm rõ. Các tế bào biểu mô dạ dày bình thường được thu thập từ dạ dày thỏ đã được nuôi cấy với H. pylori sống và/hoặc axit acetylsalicylic trong 24 giờ như một mô hình in vitro cho tổn thương tế bào biểu mô dạ dày. Tỷ lệ biểu hiện kháng nguyên Fas trong các tế bào biểu mô dạ dày được đo bằng FACScan. Trong nhóm E, nơi mà sự nhiễm H. pylori của các tế bào biểu mô được theo sau bởi điều trị bằng NSAID, tỷ lệ biểu hiện kháng nguyên Fas cao hơn đáng kể so với tỷ lệ quan sát được sau điều trị bằng H. pylori hoặc NSAID một mình. Mặc dù việc điều trị bằng thuốc đơn độc không làm tăng đáng kể tỷ lệ biểu hiện Fas so với các tế bào đối chứng. Kết quả cho thấy H. pylori và NSAID gây tổn thương tế bào dạ dày với cơ chế apoptosis qua đường phân tử Fas một cách hiệp đồng và rằng hiệu ứng này đặc biệt mạnh mẽ khi điều trị bằng NSAID được thực hiện sau nhiễm H. pylori.

Từ khóa

#Helicobacter pylori #Axit Acetylsalicylic #Apoptosis #Kháng nguyên Fas #Tế bào biểu mô dạ dày

Tài liệu tham khảo

Hopkins RJ, Girardi LS, Turney EA: Relationship between Helicobacter pylori eradication and reduced duodenal and gastric ulcer recurrence: A review. Gastroenterology 110:1244–1252, 1996 McCarthy DM: Mechanisms of mucosal injury and healing: The role of non-steroidal anti-inflammatory drugs. Scand J Gastroenterol 208:498–501, 1995 Derry S, Loke YK: Risk of gastrointestinal haemorrhage with long term use of aspirin: Meta-analysis. BMJ 321:1170–1171, 2000 Chan FK, Sung JJ, Chung SC, To KF, Yung MY, Leung VK, Lee YT, Chan CS, Li EK, Woo J: Randomised trial of eradication of Helicobacter pylori before non-steroidal antiinflammatory drug therapy to prevent peptic ulcers. Lancet 350:975–979, 1997 Santucci L, Fiorucci S, Patoia L, Di Matteo FM, Brunori PM, Morelli A: Severe gastric mucosal damage induced by NSAIDs in healthy subjects is associated with Helicobacter pylori infection and high levels of serum pepsinogens. Dig Dis Sci 40:2074–2080, 1995 Graham DY, Lidsky MD, COX AM, Evans DJ, Evans DG, Alpert L, Klein PD, Sessoms SL, Michaletz PA, Saeed ZA: Long-term nonsteroidal anti-inflammatory drug use and Helicobacter pylori infection. Gastroenterology 100:1653–1657, 1991 Hawkey CJ, Tulassay Z, Szczepanski L, van Rensburg CJ, Filipowicz-Sosnowska A, Lanas A, Wason CM, Peacock RA, Gillon KRW: Randomised controlled trial of Helicobacter pylori eradication in patients on non-steroidal anti-inflammatory drugs: HELP NSAIDs study. Lancet 352:1016–1021, 1998 Wagner S, Beil W, Westermann J, Logan RP, Bock CT, Trautwein C, Bleck JS, Manns MP: Regulation of gastric epithelial cells growth by Helicobacter pylori: Evidence for a major role of apoptosis. Gastroenterology 113:1836–1847, 1997 Tanaka M, Ito H, Adachi S, Akimoto H, Nishikawa T, Kasajima T, Marumo F, Hiroe M: Hypoxia induces apoptosis with enhanced expression of Fas antigen messenger RNA in cultured neonatal rat cardiomyocytes. Circ Res 75:426–433, 1994 Rudi J, Kuck D, Strand S, von Herbay A, Mariani SM, Krammer PH, Galle PR, Stremmel W: Involvement of the CD95 (APO-1/Fas) receptor and ligand system in Helicobacter pylori-induced gastric epithelial apoptosis. J Clin Invest 102:1506–1514, 1998 Yonehara S, Ishii A, Yonehara M: A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumor necrosis factor. J Exp Med 169:1747–1756, 1989 Covacci A, Censini S, Bugnoli M, Petracca R, Burroni D, Macchia G, Massone A, Papini E, Xiang Z, Figura N, Rappuoli R: Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer. Proc Natl Acad Sci USA 90:5791–5795, 1993 Cover TL, Tummuru MKR, Cao P, Thompson SA, Blaser MJ: Divergence of genetic sequences for vacuolating cytotoxin among Helicobacter pylori strains. J Biol Chem 269:10566–10573, 1994 Phadnis SH, Ilver D, Janzon L, Normark S, Westblom TU: Pathological significance and molecular characterization of the vacuolating toxin gene of Helicobacter pylori. Infect Immun 62:1557–1565, 1994 Awakawa T, Sugiyama T, Hisano K, Karita M, Yachi A: Detection and identification of cagA of Helicobacter pylori by polymerase chain reaction. Eur J Gastroenterol Hepatol 7(suppl 1):S75–S78, 1995 Ueda F, Kyoi T, Mimura K, Kimura K, Yamamoto M: Intercellular communication in cultured rabbit gastric epithelial cells. Jpn J Phamacol 57:321–328, 1991 Towbin H, Staehelin T, Gordon J: Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: Procedure and some application. Proc Natl Acad Sci USA 76:4350–4354, 1979 Wyllie AH: Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 284:555–556, 1980 Lanza FL, Evans DG, Graham DY: Effect of Helicobacter pylori infection on the severity of gastroduodenal mucosal injury after the acute administration of naproxen or aspirin to normal volunteers. Am J Gastroenterol 86:735–737, 1991 French LE, Hahne M, Viard I, Radlgruber G, Zanone R, Becker K, Muller C, Tschopp J: Fas and Fas ligand in embryos and adult mice: Ligand expression in several immuneprivileged tissues and co-expression in adult tissues characterized by apoptotic cell turnover. J Cell Bio 133:335–343, 1996 Houghton J, Korah RM, Condon MR, Kim KH: Apoptosis in Helicobacter pylori-associated gastric and duodenal ulcer disease is mediated via the Fas antigen pathway. Dig Dis Sci 44:465–478, 1999 Kim JM, Kim JS, Jung HC, Song IS, Kim CY: Apoptosis of human gastric epithelial cells via caspase-3 activation in response to Helicobacter pylori infection: Possible involvement of neutrophils through tumor necrosis factor alpha and soluble Fas ligands. Scand J Gastroenterol 35:40–48, 2000 Shirin H, Moss SF: Helicobacter pylori induced apoptosis. Gut 43:592–594, 1998 Moss SF, Calam J, Agarwal B, Wang S, Holt PR: Induction of gastric epithelial apoptosis by Helicobacter pylori. Gut 38:498–501, 1996 Crabtree JE, Farmery SM, Lindley IJD, Figura N, Peichl P, Tompkins DS: CagA/cytotoxin strains of Helicobacter pylori and interleukin-8 in gastric epithelial cell lines. J Clin Pathol 47:945–950, 1994 Santucci L, Fiorucci S, Giansanti M, Brunori PM, Di Matteo FM, Morelli A: Pentoxifylline prevents indomethacin induced acute gastric mucosal damage in rats: Role of tumor necrosis factor alpha. Gut 35:909–915, 1994