摘要
目的:观察粪菌移植(fecal microbiota transplantation,FMT)、粪菌移植联合果胶(fecal microbiota transplantation combine with pectin,FMTP)治疗对葡聚糖硫酸钠(dextran sodium sulphate,DSS)诱导结肠炎小鼠体重、DAI(disease activity index)指数、血清学、组织病理学等的影响以及结肠黏膜固有层巨噬细胞M1/M2的变化情况,探究粪菌移植治疗溃疡性结肠炎的可能机制。方法:C57BL/6小鼠予以3.0%DSS喂养7 d建造结肠炎模型后按比例随机分为DSS-FMT组(结肠炎模型组,6只)、DSS+FMT组(粪菌移植组,6只)、DSS+FMTP组(粪菌移植联合果胶组,6只),NC组(正常对照组,6只)予以蒸馏水喂养。第8~14 d予以DSS+FMT组、DSS+FMTP组粪菌滤液灌肠处理,0.15 m L/次,隔日1次,共4次;DSS+FMTP组同时予以5%果胶灌胃,0.2 m L/次,1次/日,总共7次。观察各组小鼠体重、疾病活动指数(DAI)、结肠长度、组织病理学、血清学、肠黏膜巨噬细胞M1/M2变化等情况。结果:DSS-FMT组分别与DSS+FMT组、DSS+FMTP组在第10 d体重(16.03+0.23 g vs 17.05±0.70 g、17.45+0.50 g)差异具有统计学意义(P<0.05);第12 d,DSS-FMT组DAI(3.00+0.63)分别与DSS+FMT组(2.33+0.52)、DSS+FMTP组(1.67+0.52)相比均明显升高(P<0.05);DSS-FMT组结肠长度(5.78+0.38)cm相较于DSS+FMT组(6.69+0.50)cm和DSS+FMTP组(7.03±0.47)cm明显缩短(P<0.05);同时,经粪菌移植干预后,与DSS-FMT组相比可以降低血清炎性细胞因子IL-6(53.28+4.40 pg/m L vs 75.35+6.78 pg/m L)、TNF-á(221.76+15.31 ng/L vs 273.10+21.20ng/L),升高抗炎因子IL-4水平(37.19+7.86 pg/m L vs 16.08+12.33 pg/m L)(P<0.05),且可以改变肠黏膜巨噬细胞M1/M2分布、比例。结论:粪菌移植及粪菌移植联合果胶治疗可以改善结肠炎小鼠一般情况、改变结肠黏膜中巨噬细胞M1/M2比例、分布;其缓解结肠炎小鼠肠道炎症可能与促进巨噬细胞M2极化有关。
Objective To investigate the effect of fecal microbiota transplantation （FMT） versus FMT combined with pectin （FMTP） on body weight, disease activity index （DAI）, serological markers, histopathology, and changes in M1/M2 macrophages in the lamina propria of the colonic mucosa in mice with colitis induced by dextran sodium sulphate （DSS）, as well as possible mechanism of FMT in the treatment of ulcerative colitis. Methods： C57BL/6 mice were fed with 3.0% DSS for 7 days to establish a model of colitis, and then these mice were randomLy divided into DSS-FMT group （colitis model group with 6 mice）, DSS ＋ FMT group （FMT group with 6 mice）, DSS ＋ FMTP group （FMT combined with pectin group with 6 mice）, and NC group （control groupwith 6 mice fed by distilled water）. On days 8-14, the mice in the DSS ＋ FMT group and the DSS ＋ FMTP group were given enema with the filtrate of fecal microbiota at a dose of 0.15 mL/time once every other day for 4 times in total, and those in the DSS＋FMTP group were also given 5 % pectin by gavage at a dose of 0.2 mL/time once a day for 7 days in total. All groups were observed in terms of body weight, DAI, length of the colon, histopathology, serological markers, and changes in M1/M2 macrophages in the colonic mucosa. Results： There was a significant difference in body weight on day 10 between the DSS-FMT group and the DSS＋FMT/DSS＋FMTP groups （16.03 ±0.23 g vs 17.05 ± 0.70/17.45 ± 0.50 g, P 〈 0.05）. On day 12, the DSS-FMT group had a significant increase in DAI compared with the DSS ＋ FMT group and the DSS ＋ FMTP group （3.00 ± 0.63 vs 2.33 ± 0.52/1.67 ± 0.52, P 〈 0.05）. Compared with the DSS ＋ FMT group and the DSS ＋ FMTP group, the DSS - FMT group had a signif-icantly shortened length of the colon （5.78 ± 0.38 cm vs 6.69 ± 0.50/7.03 ± 0.47 cm, P 〈 0.05）. Compared with the DSS - FMT group, FMT significantly reduced the serum levels of inflammatory cytokines interleukin-6 （53.28 ± 4.40 pg/mL vs 75.35 ± 6.78 pg/mL, P 〈 0.05） and tumor necrosis factor-a （221.76 ± 15.31 ng/L vs 273.10 ± 21.20 ng/ L, P 〈 0.05）, increased the serum level of interleukin-4 （37.19 ± 7.86 pg/mL vs 16.08 ± 12.33 pg/mL, P 〈 0.05）, and changed the distribution and proportion of M1/M2 macrophages in the colonic mucosa. Conclu-sions： FMT and FMTP can improve the general status of mice with colitis and change the proportion and distri-bution of M1/M2 macrophages in the colonic mucosa. They may also alleviate intestinal inflammation by promoting the polarization of M2 macrophages.
出处
《西南医科大学学报》
2017年第6期577-582,共6页
Journal of Southwest Medical University
基金
四川省科技创新苗子工程培育项目(2017032)
关键词
粪菌移植
果胶
结肠炎小鼠
巨噬细胞M2
极化
Fecal microbiota transplantation
Pectin
Mouse with colitis
M2 macrophage
Polarization
