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李前昆, 邹巍莹, 宾东华, 余炼.基于ERK/JNK通路探究参苓白术散对克罗恩病大鼠结肠黏膜氧化应激的影响[J].湖南中医药大学学报,2025,45(6):1000-1007[点击复制] |
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| 基于ERK/JNK通路探究参苓白术散对克罗恩病大鼠结肠黏膜氧化应激的影响 |
| 李前昆,邹巍莹,宾东华,余炼 |
| (湖南中医药大学, 湖南 长沙 410208;江华瑶族自治县人民医院, 湖南 永州 425500;湖南中医药大学第一附属医院, 湖南 长沙 410007) |
| 摘要: |
| 目的 探究参苓白术散通过调节细胞外信号调节蛋白激酶/c-Jun（ERK/JNK）氨基末端激酶（ERK/JNK）通路影响克罗恩病（CD）大鼠结肠炎性表达及氧化应激的机制。方法 采用随机法将60只SD大鼠均分为空白组（CG组）、模型组（M组）、美沙拉秦组（MG组）及参苓白术散高、中、低剂量组（SLZ-H、SLZ-M、SLZ-L组）。使用2,4,6-三硝基苯磺酸（TNBS）灌肠液诱导CD模型，造模成功后各组给予相应差异处理。监测每组大鼠在用药期间的体质量变化，14 d后进行结肠组织病理学观察及黏膜损伤指数（CMDI）评分，ELISA检测C反应蛋白（CRP）、白细胞介素（IL）-2、IL-8、白蛋白（ALB）、血红蛋白（Hb）、γ-干扰素（INF-γ）的含量；DHE-荧光法检测活性氧（ROS）的含量；Western blot法检测肠黏膜组织中JNK、磷酸化JNK（p-JNK）、ERK1/2、磷酸化ERK1/2（p-ERK1/2）蛋白表达水平。结果 与CG组比较，M组大鼠CMDI评分明显升高（P＜0.01），血清中IFN-γ、IL-2、IL-8、CRP水平显著升高（P＜0.01），ALB、Hb水平明显下降（P＜0.01），结肠组织中ROS水平明显升高（P＜0.01），JNK、p-JNK、ERK1/2、p-ERK1/2蛋白表达显著升高（P＜0.01）；与M组相比，MG组及SLZ-H组、SLZ-M组CMDI评分显著降低（P＜0.01），SLZ-H组IFN-γ、IL-2、IL-8、CRP水平明显下降（P＜0.01），ALB、Hb水平显著上升（P＜0.01），SLZ-M组IFN-γ、IL-2水平明显下降（P＜0.01），MG组Hb水平显著上升（P＜0.01），MG、SLZ各剂量组JNK、p-ERK1/2蛋白表达明显降低（P＜0.01），SLZ-H组、SLZ-M组p-JNK、ERK1/2蛋白表达显著降低（P＜0.01）；与MG组对比，SLZ-L组CMDI评分升高（P＜0.05），SLZ-H组IL-2明显下降（P＜0.01），IL-8和 ROS水平降低（P＜0.05），p-JNK、p-ERK1/2蛋白水平显著降低（P＜0.01），JNK、ERK1/2蛋白表达降低（P＜0.05），SLZ-M组p-ERK1/2降低（P＜0.05）。结论 参苓白术散可抑制肠道氧化应激反应，以此缓解CD大鼠肠道炎症，其作用机制可能是通过对ERK/JNK通路的抑制作用，削减ROS生成量，减少IFN-γ、IL-2、IL-8等炎症因子的释放，促使CRP水平降低，提升ALB与Hb水平。 |
| 关键词: 克罗恩病 参苓白术散 炎症因子 活性氧 细胞外信号调节蛋白激酶/c-Jun氨基末端激酶 |
| DOI：10.3969/j.issn.1674-070X.2025.06.002 |
| 投稿时间：2025-03-14 |
| 基金项目:湖南省自然科学基金高校联合基金项目（2025JJ90101）；湖南省教育厅科学研究重点项目（24A0275）。 |
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| Effects of Shenling Baizhu Powder on colonic oxidative stress in rats with Crohn's disease based on ERK/JNK pathway |
| LI Qiankun, ZOU Weiying, BIN Donghua, YU Lian |
| (Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Jianghua Yao Autonomous County People's Hospital, Yongzhou, Hunan 425500, China;The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China) |
| Abstract: |
| Objective To explore the mechanism by which Shenling Baizhu Powder (SLBZP) affects colonic inflammatory expression and oxidative stress in rats with Crohn's disease (CD) by regulating the extracellular signal-regulated kinase/c-Jun N-terminal kinase (ERK/JNK) pathway.Methods A total of 60 SD rats were randomly and evenly divided into the blank group (CG group), the model group (M group), the mesalazine group (MG group), and the high-, medium-, and low-dose SLBZP groups (SLBZP-H, SLBZP-M, and SLBZP-L groups). The CD model was induced by enema solution of 2,4,6-trinitrobenzenesulfonic acid (TNBS) and corresponding treatments were given to each group after successful modeling. The changes in body mass of rats in each group during the medication period were continuously monitored. After 14 days, colonic histopathological observation and colonic mucosal damage index (CMDI) scoring were conducted. ELISA was used to detect the content of C-reactive protein (CRP), interleukin (IL)-2, IL-8, albumin (ALB), hemoglobin (Hb), and interferon-γ (IFN-γ). The content of reactive oxygen species (ROS) was detected by DHE-fluorescence method. The protein expression levels of JNK, phosphorylated JNK (p-JNK), ERK1/2, and phosphorylated ERK1/2 (p-ERK1/2) in the intestinal mucosal tissue were measured by Western blot.Results Compared with CG group, the CMDI score of M group significantly increased (P<0.01), the serum levels of IFN-γ, IL-2, IL-8, and CRP were significantly higher (P<0.01), the levels of ALB and Hb significantly decreased (P<0.01), the level of ROS in the colonic tissue was significantly elevated (P<0.01), and the protein expressions of JNK, p-JNK, ERK1/2, and p-ERK1/2 significantly increased (P<0.01). Compared with M group, the CMDI scores of MG, SLBZP-H, and SLBZP-M groups significantly decreased (P<0.01); the levels of IFN-γ, IL-2, IL-8, and CRP in SLBZP-H group were significantly reduced (P<0.01), while the levels of ALB and Hb significantly increased (P<0.01); the levels of IFN-γ and IL-2 in SLBZP-M group decreased significantly (P<0.01); the level of Hb in MG group increased significantly (P<0.01); the protein expressions of JNK and p-ERK1/2 in MG group and all SLBZP groups were significantly downregulated (P<0.01), and the protein expressions of p-JNK and ERK1/2 in SLBZP-H and SLBZP-M groups were significantly reduced (P<0.01). Compared with MG group, SLBZP-L group showed an increase in the CMDI score (P<0.05), and the IL-2 level was significantly lower (P<0.01), the levels of IL-8 and ROS were reduced (P<0.05), the protein levels of p-JNK and p-ERK1/2 were significantly diminished (P<0.01), and the protein expressions of JNK and ERK1/2 decreased (P<0.05); p-ERK1/2 in SLSLBZP-M group was reduced (P<0.05).Conclusion SLBZP is capable of alleviating the intestinal inflammatory response in CD rats by suppressing the intestinal oxidative stress reaction. Its underlying mechanism of action may involve the inhibition of the ERK/JNK pathway, leading to a reduction in ROS generation, a decrease in the release of inflammatory cytokines such as IFN-γ, IL-2, and IL-8, a lowering of the CRP level, and an elevation in the levels of ALB and Hb. |
| Key words: Crohn's disease Shenling Baizhu Powder inflammatory factors reactive oxygen species extracellular signal-regulated protein kinase/c-Jun N-terminal kinase |
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