1.北京中医药大学东方医院,北京市丰台区方庄芳星园一区6号,100078
2.北京中医药大学中医学院
b01350@bucm.edu.cn
收稿:2025-12-14,
修回:2026-04-29,
录用:2026-01-19,
网络首发:2026-07-15,
纸质出版:2026-07-17
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高明旭,刘雷蕾,路理杰等.清肠温中方对有菌/伪无菌急性溃疡性结肠炎模型小鼠肠黏液屏障影响的比较研究[J].中医杂志,2026,67(14):1528-1537.
GAO Mingxu,LIU Leilei,LU Lijie,et al.Comparative Study on the Effects of Qingchang Wenzhong Decoction (清肠温中方) on the Intestinal Mucus Barrier in Conventional and Pseudo-Germ-Free Model Mice of Acute Ulcerative Colitis[J].Journal of Traditional Chinese Medicine,2026,67(14):1528-1537.
高明旭,刘雷蕾,路理杰等.清肠温中方对有菌/伪无菌急性溃疡性结肠炎模型小鼠肠黏液屏障影响的比较研究[J].中医杂志,2026,67(14):1528-1537. DOI: 10.13288/j.11-2166/r.2026.14.011.
GAO Mingxu,LIU Leilei,LU Lijie,et al.Comparative Study on the Effects of Qingchang Wenzhong Decoction (清肠温中方) on the Intestinal Mucus Barrier in Conventional and Pseudo-Germ-Free Model Mice of Acute Ulcerative Colitis[J].Journal of Traditional Chinese Medicine,2026,67(14):1528-1537. DOI: 10.13288/j.11-2166/r.2026.14.011.
目的
2
探讨清肠温中方治疗急性溃疡性结肠炎(UC)的作用机制。
方法
2
100只雄性C57BL/6J小鼠采用随机数字表法分为伪无菌组(45只)和有菌组(55只)。伪无菌组小鼠建立伪无菌鼠模型和急性UC模型,将造模成功的45只伪无菌急性UC模型小鼠再随机分为伪无菌模型组、伪无菌清肠温中方组、伪无菌美沙拉秦组各15只。55只有菌组小鼠再随机分为空白组(10只)及有菌模型组、有菌清肠温中方组、有菌美沙拉秦组各15只,除空白组外其余各组小鼠建立急性UC模型,空白组小鼠不做干预。实验第32天开始,伪无菌清肠温中方组、有菌清肠温中方组给予清肠温中方颗粒9.71 g/(kg·d)去离子水溶液灌胃,伪无菌美沙拉秦组、有菌美沙拉秦组给予美沙拉秦肠溶片151.67 mg/(kg·d)去离子水溶液灌胃,其余各组小鼠予去离子水0.1 ml/10 g灌胃,每日1次,共7天。实验第25天伪无菌组和有菌组随机选取6只小鼠检测体质量,并进行粪便肠道菌群16s rDNA测序,比较两组小鼠差异菌群的生物学信息[包括操作分类单元(OTUs)数量、香农(Shannon)指数、观测物种数(Observed_species)指数、系统发育多样性(PD whole tree)]。实验第39天,检测各组小鼠体质量,并进行疾病活动指数(DAI)评分;测量结肠长度、结肠湿重;HE染色观察结肠组织病理学,并进行结肠组织学病变评分;检测结肠组织黏液屏障指标黏多糖、黏蛋白2(MUC2)表达。
结果
2
实验第25天,伪无菌组和有菌组小鼠体质量比较差异无统计学意义(
P
>0.05);与有菌组比较,伪无菌组OTUs数量、Shannon指数、Observed_species指数、PD whole tree均显著降低(
P
<0.01)。实验第39天,与空白组比较,有菌模型组小鼠体质量降低、DAI评分升高,结肠湿重增加、结肠长度降低,结肠组织学病变评分显著增加,黏多糖、MUC2表达降低(
P
<0.01),而伪无菌模型组上述各指标差异均无统计学意义(
P
>0.05)。与有菌模型组比较,有菌清肠温中方组上述各指标均显著改善,有菌美沙拉秦组仅DAI评分、结肠湿重降
低(
P
<0.01)。伪无菌模型组、伪无菌清肠温中方组、伪无菌美沙拉秦组小鼠各指标差异均无统计学意义(
P
>0.05)。
结论
2
清肠温中方可能通过调控肠道菌群促进肠黏膜屏障重建,从而发挥治疗急性UC的作用。
Objective
2
To explore the mechanisms of
Qingchang Wenzhong Decoction
(清肠温中方, QWD) in treating ulcerative colitis (UC).
Methods
2
A total of 100 male C57BL/6J mice were assigned to a pseudo-germ-free group (n=45) and a conventional group (n=55) using a random number table. Pseudo-germ-free model was established by giving antibiotic treatment and subsequently subjected to acute UC induction. After the model was successfully established, the 45 pseudo-germ-free acute UC mice were randomly allocated to a pseudo-germ-free model group, a pseudo-germ-free QWD group, and a pseudo-germ-free mesalazine group, with 15 mice in each group. The 55 conventional mice were randomly divided into a normal control group (n=10), as well as a conventional model group, a conventional QWD group, and a conventional mesalazine group, with 15 mice in each group. Except for the normal control group, acute UC models were established in all other groups. Mice in the control group received no intervention. From day 32 of the experiment, mice in the pseudo-germ-free QWD group and the conventional QWD group were administered with QWD granules at a dose of 9.71 g/(kg·d) by gavage with deionized water, while those in the pseudo-germ-free mesalazine group and the conventional mesalazine group were given mesalazine enteric-coated tablets at a dose of 151.67 mg/(kg·d) by gavage. Mice in the remaining groups received an equal volume of deionized water once daily for 7 consecutive days. On day 25 of the experiment, six mice were randomly selected from both the pseudo-germ-free group and the conventional group to measure body weight, and fecal samples were collected for 16S rDNA sequencing to compare differences in gut microbiota, including operational taxonomic units (OTUs), Shannon index, Observed_species index, and phylogenetic diversity (PD whole tree). On day 39, body weight was measured in all groups, and the disease activity index (DAI) was evaluated. Colon length and colon wet weight were recorded. Histopathological changes in colonic tissues were assessed by hematoxylin and eosin (HE) staining, and histological injury scores were determined. In addition, the expression levels of mucopolysaccharides and mucin 2 (MUC2) in colonic tissues were measured.
Results
2
On day 25, there was no significant difference in body weight between the pseudo-germ-free group and the conventional microbiota group (
P
>0.05). Compared to the conventional microbiota group, the pseudo-germ-free group showed significantly reduced OTUs, Shannon index, Observed_species index, and PD whole tree (
P
<0.01). On day 39, compared to the normal control group, mice in the conventional model group showed a significant decrease in the body weight and an increase in DAI, along with increased colon wet weight, shortened colon length, markedly elevated histopathological scores, and reduced expression of mucopolysaccharides and MUC2 (
P
<0.01). In contrast, no significant differences were observed in these parameters in the pseudo-germ-free model group (
P
>0.05). Compared to the conventional model group, the conventional QWD group showed significant improvement in all measured parameters, whereas the conventional mesalazine group showed reductions only in DAI scores and colon wet weight (
P
<0.01). No statistically significant differences were observed among the pseudo-germ-free model group, the pseudo-germ-free QWD group, and the pseudo-germ-free mesalazine group (
P
>0.05).
Conclusion
2
QWD may promote the reconstruction of the intestinal mucus barrier by regulating the intestinal flora, thereby exerting a therapeutic effect on acute UC.
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