Curcumin alleviates indomethacin-ciprofloxacin combination-induced small intestinal injury in mice by modulating Treg/Th17 balance and synergistically treats severe traumatic infections

CHEN Daiqi; YU Jing; XIA Yu; LIU Guochang; WANG Haiyan; LI Suiyan; YAN Jun

doi:10.16016/j.2097-0927.202511042

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Curcumin alleviates indomethacin-ciprofloxacin combination-induced small intestinal injury in mice by modulating Treg/Th17 balance and synergistically treats severe traumatic infections

Military Medicine | 更新时间：2026-02-04

- Curcumin alleviates indomethacin-ciprofloxacin combination-induced small intestinal injury in mice by modulating Treg/Th17 balance and synergistically treats severe traumatic infections
- Journal of Army Medical University Vol. 48, Issue 2, Pages: 116-127(2026)
- 作者机构：
  
  1.西南交通大学生命科学与工程学院，四川成都
  2.陆军军医大学大坪医院特殊环境战伤防治研究室，创伤与化学中毒全国重点实验室，重庆
- 作者简介：
  
  LI Suiyan, E-mail： lisuiyan@swjtu.edu.cn
  YAN Jun, E-mail：13883092250@163.com
- 基金信息：
  
  General Program Natural Science Foundation of Chongqing(CSTB2023NSCQ-MSX0014);the Special Project of Science and Technology Innovation Capacity Promotion of Army Medical University(2019XYY22)
- DOI：10.16016/j.2097-0927.202511042
  CLC： R181.23;R63;R656.7
- Received：07 November 2025，
  
  Revised：2026-01-04，
  
  Accepted：04 January 2026，
  
  Published：30 January 2026
- 稿件说明：
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陈代琦，余静，夏雨，等.姜黄素通过调节Treg/Th17平衡减轻吲哚美辛-环丙沙星联用所致小鼠小肠损伤并协同治疗严重创伤感染［J］.陆军军医大学学报，2026，48（02）：116-127.DOI：10.16016/j.2097-0927.202511042.

CHEN D Q，YU J，XIA Y，et al.Curcumin alleviates indomethacin-ciprofloxacin combination-induced small intestinal injury in mice by modulating Treg/Th17 balance and synergistically treats severe traumatic infections［J］.J Army Med Univ，2026，48（02）：116-127.DOI：10.16016/j.2097-0927.202511042.
陈代琦，余静，夏雨，等.姜黄素通过调节Treg/Th17平衡减轻吲哚美辛-环丙沙星联用所致小鼠小肠损伤并协同治疗严重创伤感染［J］.陆军军医大学学报，2026，48（02）：116-127.DOI：10.16016/j.2097-0927.202511042. DOI：

CHEN D Q，YU J，XIA Y，et al.Curcumin alleviates indomethacin-ciprofloxacin combination-induced small intestinal injury in mice by modulating Treg/Th17 balance and synergistically treats severe traumatic infections［J］.J Army Med Univ，2026，48（02）：116-127.DOI：10.16016/j.2097-0927.202511042. DOI：

摘要

目的

探讨姜黄素（curcumin，CUR）对吲哚美辛（indomethacin， IND）联用环丙沙星（ciprofloxacin， CIP）治疗严重创伤感染中小肠损伤的作用及其机制。

方法

将8周龄雄性C57BL/6小鼠完全随机分为4组（生存率观察，

=10；其余指标，

=8）：对照组、创伤感染组［失血+骨折+铜绿假单胞菌（

Pseudomonas aeruginosa

，

）感染］、IND+CIP治疗组和IND+CIP+CUR治疗组。观察各组小鼠建模后72 h内生存率；收集建模24 h后外周血、小肠组织及肠系膜淋巴结（mesenteric lymph node， MLN），观察各组小肠长度变化、出血状况和粘连情况；稀释涂布平板法检测各组细菌载量；HE染色观察各组肠道组织病理学改变；ELISA分别检测各组血清和小肠匀浆炎症因子水平（IL-1β、IL-6、IL-10和TNF-α）；血液生化指标检测各组肝功、肾功和心功能重要指标。流式细胞术检测各组MLN中CD4

T细胞中IFN-γ、IL-4、TGF-β和IL-17阳性百分比；qPCR检测各组叉头状蛋白P3（forkhead box protein P3， FOXP3）和维甲酸受体相关孤儿受体γ（retinoic acid receptor-related orphan receptor γ， RORγ）-

mRNA表达。

结果

IND+CIP治疗组和IND+CIP+CUR治疗组均能显著提高严重创伤感染小鼠生存率（

0.05），CUR联用能够降低小鼠细菌载量（

0.01）。IND+CIP治疗组会引发小肠损伤，并随时间推移呈现加重趋势，表现为小肠TNF-α（

0.01）、IL-6（

0.01）和IL-1β水平升高（

0.05），IL-10水平降低（

0.05），并伴有小肠病理损伤；IND+CIP+CUR治疗组能显著逆转小肠损伤，降低炎性因子水平（

0.01），使小肠结构恢复正常，相关血液生化指标与IND+CIP治疗组无明显差异。与IND+CIP治疗组相比，IND+CIP+CUR治疗组CD4

T细胞中

FOXP3

表达增高（

0.01），

RORγ

表达降低（

0.01）。

结论

CUR联用IND和CIP可有效治疗严重创伤感染，同时拮抗IND和CIP疗法中出现的小肠损伤，并对重要脏器功能无明显副作用，其机制可能与调节性T细胞（regulatory T cell， Treg）-辅助性T细胞17（helper T cell 17， Th17）平衡有关。

Abstract

Objective

To investigate the effect and underlying mechanisms of curcumin (CUR) on small intestinal injuries associated with severe traumatic infections after combined treatment of ciprofloxacin (CIP) and indomethacin (IND).

Methods

Adult male C57BL/6 mice (8 weeks old) were randomly divided into (10 animals for survival rate observation

10 for other indicators) control group

model group [hemorrhage+ fracture+

Pseudomonas aeruginosa (PA)

infection

]

IND+CIP treatment group

and IND+ CIP+CUR treatment group. The survival rates within 72 h post-modelling were observed across all groups. At 24 h post-modelling

peripheral blood samples

small intestinal tissues and mesenteric lymph nodes (MLN) were harvested. Small intestinal length

hemorrhagic status

and adhesions were also observed grossly in each group. Bacterial load was determined

via

dilute plating. HE staining was used to observe histopathological alterations in intestinal tissues across groups. ELISA was employed to measure the contents of inflammatory cytokines

IL-1β

IL-6

IL-10 and TNF-α in the serum and small intestinal homogenate of each group. Liver

renal

and cardiac functions were evaluated by measuring key biochemical indicators. Flow cytometry was applied to measure the percentages of IFN-γ

IL-4

TGF-β

and IL-17 positive cells within CD4

T cells in the MLN. Real-time quantitative polymerase chain reaction (qPCR) was performed to detect the mRNA expression of

forkhead box protein P3

(FOXP3

) and

retinoic acid receptor-related orphan receptor gamma (RORγ)

in each group.

Results

Both the IND+CIP treatment group and the IND+CIP+CUR treatment group significantly improved survival rates in mice with severe traumatic infections (

0.05). CUR addition reduced bacterial load in the mice (

0.01). The IND+CIP treatment group exhibited small intestinal injury

which worsened over time

manifested by elevated contents of TNF-α (

0.01)

IL-6 (

0.05)

and IL-1β (

0.05) and decreased IL-10 (

0.01) in the small intestine tissues

accompanied with pathological damage in the small intestine. The IND+CIP+CUR treatment group had significantly reversed small intestinal injury

reduced inflammatory factor levels (

0.01)

and restored normal small intestinal structure

showing no significant differences in relevant blood biochemical indicators when compared to the IND+CIP treatment group. The expression of

FOXP3

was increased and that of

RORγ

was decreased

in CD4

T cells from the IND+CIP+CUR treatment group than the IND+CIP treatment group (both

0.01).

Conclusion

The combination of CUR with IND and CIP can effectively alleviate severe traumatic infections

while antagonize small intestinal damage observed in IND and CIP therapy

with no significant adverse effects on vital organ functions. This mechanism may be related to the balance between regulatory T (Treg) cells and T helper 17 (Th17) cells.

关键词

Keywords

references

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