Page 87 - 中国全科医学2022-15

·1876· http://www.chinagp.net E-mail:zgqkyx@chinagp.net.cn

【Abstract】 Background As an intractable disease recognized by the WHO，current available treatments have
limitations for ulcerative colitis（UC）. Although the effectiveness of fecal microbiota transplantation （FMT） has been
confirmed，the reported efficacies are various. Objective To compare the effect of FMT between a mouse model of common UC
and a mouse model of damp-heat UC，and the medicinal flavor of fecal microbiota（new jinzhi）. Methods This experiment
was implemented from December 9th to 28th，2019. Thirty-five male SPF C57BL/6 mice were equally divided into seven groups:
normal control group（no intervention），common UC model（CUCM） group（received interventions to be a CUCM according
to the requirements），CUCM+FMT group（received interventions to be a CUCM successfully，then received an enema of
0.2 ml prepared fecal microbiota solution），CUCM+5-aminosalicylic acid（5-ASA） group（received interventions to be a
CUCM successfully，then received an enema of 0.019 5 g/ml 5-ASA），damp-heat UC model（DUCM） group（received
interventions to be a DUCM according to the requirements），DUCM+FMT group（received interventions to be a DUCM
successfully，then received an enema of 0.2 ml prepared fecal microbiota solution），and DUCM+5-ASA group（received
interventions to be a DUCM successfully，then received an enema of 0.019 5 g/ml 5-ASA）. The intestinal tissues of each group
of mice were taken out when the experiment ended，and were stained with H&E for observing the morphology，and ultrastructure
of them was observed using transmission electron microscope，Th1 and Th2 cells in them were detected using flow cytometry，and
microbial community in them were detected using high-throughput 16S rRNA gene sequencing. Routine blood test was conducted
to measure the levels of white blood cell count（WBC），red blood cell count（RBC），platelet count（PLT） and hemoglobin
（HGB）. Nimodipine method was used to evaluate the efficacy index before and after intervention. Results The mice in each
group were successfully established. The morphology of intestinal tissues stained with H&E：the intestinal mucosal surface of
CUCM group and DUCM group had different degrees of defect or shedding and necrosis，while the intestinal mucosa was basically
intact in CUCM+FMT group，CUCM+5-ASA group，DUCM+FMT group and DUCM+5-ASA group. The DUCM+FMT group
had more neatly arranged and compacted glands than did CUCM+FMT group. The ultrastructure of intestinal tissue observed using
transmission electron microscope：the surface microvilli of epithelial cells in CUCM and DUCM groups were sparse with decreased
goblet cells. The CUCM+FMT，CUCM+5-ASA，DUCM+FMT and DUCM+5-ASA groups had denser microvilli with more goblet
cells. Compared with the CUCM+FMT group，the DUCM+FMT group had denser microvilli and more goblet cells. Th1 and Th2
cell contents：there were significant differences in Th1 and Th2 cell contents，WBC，RBC，PLT and HGB across all groups of
mice（P<0.001）. Efficacy analysis：the efficacy index of CUCM+5-ASA group，DUCM+FMT group or DUCM+5-ASA group
was better than that of CUCM+FMT group （P<0.05）. Microbial community analysis：the genus with significantly decreased
abundance in CUCM and DUCM groups was Ruminococcus，and the increased abundance was Akkermansia. The CUCM+FMT
and DUCM+FMT groups had a tendency of gradually increasing similarities to the control group，indicating that the intestinal
flora of these two groups were improving. Conclusion FMT were effective for mice models of UC，especially for the mice model
of damp-heat UC. The new jinzhi has a bitter and cold flavor，which may work by regulating the intestinal flora to improve the
Th1/Th2 balance for therapeutic purposes.
【Key words】 Colitis，ulcerative；Fecal microbiota transplantation；5-aminosalicylic acid；Microflora diversity；
Th1-Th2 balance；New jinzhi

溃疡性结肠炎（ulcerative colitis，UC）是一种慢性 良反应较强，且病情容易反复，生物制剂价格昂贵，
非特异性免疫性疾病，隶属于炎症性肠病（inflammatory 经济成本太高。近年来，粪菌移植（fecal microbiota
bowel disease，IBD）的范畴，是消化系统的常见病及疑 transplantation，FMT）成为研究热门话题，其原理为将
难病 ［1-2］ ，主要以腹痛、腹泻、黏液脓血便、里急后重 健康人粪便中的功能菌群，移植入患者胃肠道内，重建
等临床表现为主 ［3］ ，反复发作是该疾病特点，多见于 具有正常功能的肠道菌群，治疗肠道及肠道外某些疾病。
直肠和乙状结肠，青壮年为好发人群。UC 的发病目前 该方法由来已久，2013 年美国食品药品监督管理局将
在全世界呈逐年上升的趋势，但 UC 的病因、发病机制 治疗难辨梭状芽孢杆菌感染写入指南，是对其安全性及
尚不明确。现代医学认为与遗传、环境、心理等因素相 有效性的认证，适应证得到进一步扩展 ［7-8］ 。多数学者
关，进而导致肠黏膜屏障受损，神经内分泌功能失调和 虽已经证实 FMT 治疗 UC 疗效的可靠性，但仍有部分
免疫失衡，从而引起肠黏膜局部溃疡而发病 ［4］ 。 学者对 FMT 治疗 UC 的疗效提出质疑，说其总体有效
UC 目前还没有治愈的方法，基本治疗原则以控 率偏低。
制症状为主，治疗药物包括氨基水杨酸制剂、糖皮质 针对 FMT 治疗 UC 疗效参差不齐的原因，笔者基
激素类、免疫抑制剂及生物制剂等 ［5-6］ 。常规药物不 于中医理论，发现金汁与 FMT 有异曲同工之效 ［9］ 。