Role of intestinal bacteria in small intestinal ulcer formation and prevention in rats treated with a nonsteroidal antiinflammatory drug.

肠道细菌在接受非甾体抗炎药治疗的大鼠小肠溃疡形成和预防中的作用。

• 批准号: 06670296
• 负责人: OHNISHI Yoshinari
• 金额: $ 1.34万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670296/
• 关键词: Nonsteroidal antiinflammatry drug; Small intestinal ulcer; Intestinal bacteria; Germ-free rats; Gnotobiotes; Lactobacillus acidophilus; Bifidobacterium adolescentis; Escherichia coli

This study examined the role of intestinal bacteria in induction and repression of ulcer formation in the ileum of rats treated with one of the nonsteroidal antiinflammatry drugs (NSAIDs), 5-bromo-2-(4-fluorophenyl)-3-(4-methylsulfonylphenyl) thiophene (BFMeT). BFMeT was administered by intragastric gavage once at doses of 500-1500 mg/kg of body weight in a volume of 10 ml/kg to Wistar rats treated with and without antibiotics (bacitracin, neomycin, streptomycin), germ-free rats and gnotobiotic rats, and 72 hours later their gastrointestinal tracts were examined for ulcer formation. Single oral administration of BFMeT induced ileal ulcers in specific pathogen-free rats. However, the rats given antibiotics to reduce the intestinal bacteria had no ulcers.BFMeT-treated germ-free rats and gnotobiotic rats mono-associated with Bifidobacterium adolescentis or Lactobacillus acidophilus also had no intestinal ulcers. However, the drug induced ileal ulcers in gnotobiotic rats mono-associated wi … More th Eubacterium limosum or Escherichia coli. The number of viable microorganisms in the ulcerated ileum was 13.6-fold higher in the aerobic culture and 8.8-fold higher in the anaerobic culture when compared with that in the normal rats. An overnight culture of B.adolescentis or L.acidophilus or yogurt containing Bifidobacterium breve and Streptococcus thermophilus, when given as drinking water, inhibited the ulcer formation in the ileum of rats treated with BFMeT.Gram staining of the ileal contents of normal rats revealed that 97.4% of the stained microorganisms were Gram-positive rods and only 1.2% were Gram-negative rods. In the group of rats with ulcers induced by BFMet, the Gram-positive rods decreased by 56.4% and the Gram-negative rods including Escherichia coli, Klebsiella, Proteus and Bacteroides increased by 37.3%. However, in the group of rats administered the Bifidobacterium culture, the Lactobacillus culture or yogurt, percentages of the Gram-negative rods were decreased. Although Lactobacillus was a major bacterium in the ileum of normal rats, the Gram-negative facultatively anaerobic rods Escherichia coli, Klebsiella and Proteus were increased in the ulcerated ileum of rats treated with BFMeT,suggesting that these bacteria are associated with the ulcer formation in rats treated with NSAIDs, and that Lactobacillus and Bifidobacterium inhibit it by repressing the growth of ulcer-inducing bacteria. Less

本研究检查了接受非甾体类抗炎药 (NSAID) 5-溴-2-(4-氟苯基)-3-(4-甲基磺酰苯基)噻吩 (BFMeT) 治疗的大鼠回肠溃疡形成中肠道细菌的作用。 BFMeT以500-1500mg/kg体重的剂量和10ml/kg的体积对使用和不使用抗生素(杆菌肽、新霉素、链霉素)处理的Wistar大鼠、无菌大鼠和无菌大鼠灌胃一次，72小时后检查其胃肠道溃疡形成情况。在特定无病原体大鼠中单次口服 BFMeT 诱导回肠溃疡。然而，给予抗生素以减少肠道细菌的大鼠没有出现溃疡。BFMeT处理的无菌大鼠和与青春双歧杆菌或嗜酸乳杆菌单一相关的无菌大鼠也没有出现肠道溃疡。然而，该药物在与利莫苏姆真杆菌或大肠杆菌单一相关的限生大鼠中引起回肠溃疡。与正常大鼠相比，需氧培养中溃疡回肠中的活微生物数量高出13.6倍，厌氧培养中高出8.8倍。青春期双歧杆菌或嗜酸乳杆菌的过夜培养物或含有短双歧杆菌和嗜热链球菌的酸奶，当作为饮用水给予时，抑制了用 BFMeT 处理的大鼠回肠中的溃疡形成。对正常大鼠回肠内容物进行革兰氏染色显示，97.4% 的染色微生物是革兰氏阳性杆状微生物，并且只有 1.2% 为革兰氏阴性杆菌。在BFMet诱发溃疡的大鼠组中，革兰氏阳性杆菌减少了56.4%，革兰氏阴性杆菌包括大肠杆菌、克雷伯氏菌、变形杆菌和拟杆菌增加了37.3%。然而，在给予双歧杆菌培养物、乳杆菌培养物或酸奶的大鼠组中，革兰氏阴性杆菌的百分比下降。虽然乳酸杆菌是正常大鼠回肠中的主要细菌，但在用 BFMeT 治疗的大鼠溃疡回肠中，革兰氏阴性兼性厌氧杆菌、克雷伯氏菌和变形杆菌增加，表明这些细菌与用 NSAIDs 治疗的大鼠的溃疡形成有关，并且乳酸菌和 双歧杆菌通过抑制溃疡诱导细菌的生长来抑制它。较少的

项目成果

M.Uejima,T.Kinouchi,Y.Ohnishi et al.: "Role of intestinal bacteria in ileal ulcer formation in rats treated with a nonsteroidal antiinflammatory drug." Microbiol Immunol.,. (発表予定).

M. Uejima、T. Kinouchi、Y. Ohnishi 等人：“用非类固醇抗炎药治疗的大鼠肠道细菌在回肠溃疡形成中的作用”，（即将出版）。

K. Kataoka, T. Kinouchi, S. Akimoto and Y. Ohnishi: "Bioactivation of cysteine conjugates of l-nitropyrene oxides by cysteine conjugate β-lyase purified from Peptostreptococcus magnus." Appl. Environ. Microbiol.61. 3781-3787 (1995)

K. Kataoka、T. Kinouchi、S. Akimoto 和 Y. Ohnishi：“从消化链球菌环境微生物中纯化的半胱氨酸缀合物 β-裂合酶对 L-硝基芘氧化物的生物活化。” 3781-3787（1995）

大西克成: "腸内菌の代謝" ヘルシスト. 17(3). 64-69 (1994)

Katsunari Onishi：“肠道细菌的代谢”Healthist 17(3) (1994)。

K.Kataoka,T.Kinouchi,S.Akimoto and Y.Ohnishi: "Bioactivation of cysteine conjugates of 1-nitropyrene oxides by cysteine conjugate β-lyase purified from Peptostreptococcus magnus." Appl.Environ.Microbiol.,. 61,. 3781-3787 (1995)

K. Kataoka、T. Kinouchi、S. Akimoto 和 Y. Ohnishi：“从消化链球菌中纯化的半胱氨酸结合物 β-裂合酶对 1-硝基芘氧化物的半胱氨酸结合物进行生物活化。” 61、3781-3787(1995)

Motoo Uejima, Takemi Kinouchi, Keiko Kataoka, Isao Hiraoka and Yoshinari Ohnishi: "Role of intestinal bacteria in ileal ulcer formation in rats treated with a nonsteroidal antiinflammatory drug." Microbiol Immunol.(To be submitted). (1996)

Motoo Uejima、Takemi Kinouchi、Keiko Kataoka、Isao Hiraoka 和 Yoshinari Ohnishi：“肠道细菌在接受非类固醇抗炎药治疗的大鼠回肠溃疡形成中的作用。”