| 引用本文: |
刘晓娟, 王晋, 陈娜, 潘霞, 刘莎莎.基于Nrf2/AKR1B10信号通路探讨姜黄素对吲哚美辛诱导的大鼠急性小肠损伤的保护效应[J].湖南中医药大学学报,2026,46(9):1816-1824[点击复制] |
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| 基于Nrf2/AKR1B10信号通路探讨姜黄素对吲哚美辛诱导的大鼠急性小肠损伤的保护效应 |
| 刘晓娟,王晋,陈娜,潘霞,刘莎莎 |
| (湖南师范大学附属长沙市妇幼保健院, 湖南 长沙 410007) |
| 摘要: |
| 目的 探讨姜黄素对吲哚美辛诱导的大鼠急性小肠损伤的保护作用及潜在作用机制。方法 将40只雄性SD大鼠采用完全随机分组法分为对照组、模型组、小檗碱组（小檗碱，60 mg/kg）、姜黄素低剂量组（姜黄素，50 mg/kg）和姜黄素高剂量组（姜黄素,100 mg/kg），每组8只；对照组皮下注射生理盐水，其余组大鼠均皮下注射吲哚美辛（7.5 mg/kg，每日1次，连续2 d）以构建急性小肠损伤模型；各组大鼠自造模前3天起连续灌胃给予相应药物或生理盐水9 d，每天1次。造模成功后，每日监测各组大鼠体质量变化，观察各组大鼠大小便状态。HE染色观察各组大鼠病理形态学改变；ELISA检测各组大鼠小肠组织中炎症因子肿瘤坏死因子-ɑ（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）水平以及血清中氧化应激相关因子超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-Px）活性；采用免疫荧光法和Western blot检测醛酮还原酶家族1成员B10（AKR1B10）、紧密连接蛋白3（Claudin-3）、闭锁小带蛋白-1（ZO-1）、血红素加氧酶-1（HO-1）、核因子红细胞2相关因子2（Nrf2）、Kelch样环氧氯丙烷相关蛋白-1（Keap1）蛋白的表达水平。结果 HE染色病理结果显示，模型组大鼠小肠黏膜呈现典型损伤特征：绒毛上皮细胞排列紊乱并伴有核固缩，基底膜完整性破坏，固有层可见弥漫性炎症细胞浸润，符合肠黏膜损伤模型构建标准。姜黄素各剂量组大鼠小肠黏膜结构均改善，主要表现为绒毛高度回升、炎症浸润程度减轻。与对照组相比，模型组大鼠的TNF-α、IL-6、IL-1β、MDA水平显著升高（P<0.001），SOD、GSH-Px、AKR1B10、ZO-1、Claudin-3、Nrf2、HO-1、Keap1水平显著降低（P<0.05，P<0.01，P<0.001）。与模型组相比，姜黄素各剂量组大鼠的TNF-α、IL-6、IL-1β、MDA水平显著降低（P<0.05，P<0.01，P<0.001），SOD、GSH-Px、AKR1B10、ZO-1、Claudin-3、Nrf2、HO-1、Keap1水平显著升高（P<0.05，P<0.01，P<0.001）。结论 姜黄素对吲哚美辛诱导的大鼠急性小肠损伤具有保护作用，其作用机制可能与激活Nrf2/AKR1B10信号通路、上调紧密连接蛋白ZO-1和Claudin-3表达、减轻炎症反应与氧化应激有关。 |
| 关键词: 急性小肠损伤|姜黄素|非甾体抗炎药|Nrf2/AKR1B10信号通路 |
| DOI：10.3969/j.issn.1674-070X.2026.09.009 |
| 投稿时间：2026-08-03 |
| 基金项目:湖南省自然科学基金项目(2026JJ82229,2025JJ80514);长沙市卫生健康委中医药科研计划项目(SB2024-077)。 |
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| Protective effects of curcumin on indomethacin-induced acute small intestinal injury in rats based on the Nrf2/AKR1B10 signaling pathway |
| LIU Xiaojuan, WANG Jin, CHEN Na, PAN Xia, LIU Shasha |
| (Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, Changsha, Hunan 410007, China) |
| Abstract: |
| Objective To investigate the protective effect and underlying mechanism of curcumin on indomethacin-induced acute small intestinal injury in rats. Methods Forty male SD rats were randomly divided into the control group, model group, berberine group (berberine, 60 mg/kg), low-dose curcumin group (curcumin, 50 mg/kg), and high-dose curcumin group (curcumin, 100 mg/kg), with eight rats in each group. Rats in the control group were subcutaneously injected with normal saline, while those in the other groups were subcutaneously injected with indomethacin (7.5 mg/kg, once daily for two consecutive days) to establish the acute small intestinal injury model. Starting three days before modeling, rats in each group were intragastrically treated with the corresponding drugs or normal saline once daily for nine consecutive days. After successful modeling, body mass changes and the state of urine and feces were monitored daily. HE staining was used to observe the pathomorphological changes in each group. ELISA was used to detect the levels of inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in small intestinal tissue, as well as the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the level of malondialdehyde (MDA) in serum. The protein expression levels of aldo-keto reductase family 1 member B10 (AKR1B10), Claudin-3, zonula occludens-1 (ZO-1), heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nrf2), and Kelch-like ECH-associated protein 1 (Keap1) were detected by immunofluorescence and Western blot. Results HE staining showed that the small intestinal mucosa of the model group presented typical injury features: disordered arrangement of villous epithelial cells with nuclear pyknosis, disrupted basement membrane integrity, and diffuse inflammatory cell infiltration in the lamina propria, which met the criteria for establishing an intestinal mucosal injury model. The small intestinal mucosal structure was improved in all curcumin groups, mainly manifested as restored villous height and alleviated inflammatory infiltration. Compared with the control group, the levels of TNF-α, IL-6, IL-1β, and MDA in the model group were significantly increased (P<0.001), while the levels of SOD, GSH-Px, AKR1B10, ZO-1, Claudin-3, Nrf2, HO-1, and Keap1 were significantly decreased (P<0.05, P<0.01, P<0.001). Compared with the model group, the levels of TNF-α, IL-6, IL-1β, and MDA in all curcumin groups were significantly decreased (P<0.05, P<0.01, P<0.001), while the levels of SOD, GSH-Px, AKR1B10, ZO-1, Claudin-3, Nrf2, HO-1, and Keap1 were significantly increased (P<0.05, P<0.01, P<0.001). Conclusion Curcumin exerts a protective effect on indomethacin-induced acute small intestinal injury in rats, and its mechanism may be related to activating the Nrf2/AKR1B10 signaling pathway, up-regulating the expression of the tight junction proteins ZO-1 and Claudin-3, and alleviating inflammatory response and oxidative stress. |
| Key words: acute small intestinal injury|curcumin|nonsteroidal anti-inflammatory drugs|Nrf2/AKR1B10 signaling pathway |
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