米诺环素对氟尿嘧啶诱导的小鼠肠黏膜炎的保护作用研究  

Protective effects of Minocycline on 5-Fluorouracil-induced intestinal mucositis in mice

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作  者:黄义新[1] 刘炜[1] HUANG Yixin;LIU Wei(Department of Pharmacy, Beijing Shijitan Hospital Affiliated to Capital Medical University, Beijing 100038, China)

机构地区:[1]首都医科大学附属北京世纪坛医院药剂科,北京100038

出  处:《中国医药导报》2019年第10期20-24,共5页China Medical Herald

基  金:首都卫生发展科研专项项目-自主创新(首发2014-2-2081)

摘  要:目的研究米诺环素对氟尿嘧啶(5-Fu)诱导的肠黏膜炎的保护作用。方法 40只雄性Balb/c小鼠,随机分为5组,正常组、模型组、米诺环素低剂量组及高剂量组,每组10只。模型组由连续腹腔注射5-Fu(80 mg/kg)3 d诱导,治疗组同时灌胃给予30 mg/kg或60 mg/kg的米诺环素。测定小鼠体质量、腹泻指数,同时对小鼠空肠进行HE染色,测定小肠黏膜中的促炎性细胞因子,并对小鼠肠内容物中的短链脂肪酸进行测定,进而评价米诺环素对小鼠肠黏膜炎的保护作用。结果高剂量米诺环素可显著增加肠黏膜炎模型小鼠的体重(P <0.01),降低其腹泻指数(P <0.01),增加模型小鼠的空肠绒毛长度(P <0.01)。此外高剂量米诺环素可显著抑制肠黏膜中的IL-6(P <0.05)和TNF-α(P <0.01)的表达,同时增加小鼠肠内容物中丁酸及乙酸的含量(P <0.01)。结论米诺环素具有确切的肠黏膜保护作用,其作用与其抗炎及促进短链脂肪酸的生成有关。Objective Forty investigate the protective effect of Minocycline on 5-Fu induced intestinal mucostitis. Methods 40 male Balb/c mice were randomly divided into four groups (n = 10), Control group, 5-Fu induced mucositis model, high dose or low dose of Minocycline treated group. After the mice were intraperitoneal administrated with 80 mg/kg 5-Fu for 3 days and simultaneously treated with 30 or 60 mg/kg orally in Balb/c mice, the body weight loss, diarrhea scores, and HE stain of the intestinal, pro-inflammatory cytokines in intestine tissue and short chain fatty acids in colon contents were also determined. Results Data from this study indicated that high dose minocycline could attenuate the 5-Fu induced body weight loss (P < 0.01), and lower the diarrhea scores (P < 0.01). Also minicycline in high dose increased the intestinal vill length (P < 0.01), decreased the IL-6 (P < 0.05) and TNF-α(P < 0.01). In the colon contents, Minocycline could significantly increase the SCFAs concentration, especially for aceticacid butyricacid (P < 0.01). Conclusion All these results demonstrated that Minocycline exert protective effects on 5-Fu induced intestinal damage in mice, and these protective effects may partially oriented from its anti-inflammatory effects and enhancing short chain fatty acid production.

关 键 词:米诺环素 氟尿嘧啶 肠黏膜炎 短链脂肪酸 

分 类 号:R730.53[医药卫生—肿瘤]

 

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