| 李跃文,万强.绿原酸调控巨噬细胞极化治疗溃疡性结肠炎的机制研究[J].浙江中医药大学学报,2023,47(9):969-975, 1001. |
| 绿原酸调控巨噬细胞极化治疗溃疡性结肠炎的机制研究 |
| Mechanism Research of Chlorogenic Acid on Treating Ulcerative Colitis via Regulating Macrophage Polarization |
| DOI：10.16466/j.issn1005-5509.2023.09.001 |
| 中文关键词: 绿原酸 葡聚糖硫酸钠 溃疡性结肠炎 Wnt5a/NPC1信号通路 巨噬细胞极化 炎症反应 |
| 英文关键词: chlorogenic acid dextran sulfate sodium ulcerative colitis Wnt5a/NPC1 signaling pathway macrophage polarization inflammatory response |
| 基金项目:国家自然科学基金项目(81660770)；江西省卫生健康委科技计划项目(202310664)；江西省教育厅科学技术研究项目(GJJ190654)；金华市科技计划项目(2020-4-057) |
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| 中文摘要: |
| [目的] 探讨绿原酸(chlorogenic acid，CGA)对葡聚糖硫酸钠(dextran sulfate sodium，DSS)诱导的溃疡性结肠炎(ulcerative colitis，UC)的治疗作用及分子机制。[方法] C57BL/6小鼠50只，用3%DSS腹腔注射7 d，建立UC动物模型并随机分为5组，除UC模型组外，其余4组分别给予柳氮磺胺吡啶(sulfasalazine，SZ)100 mg/kg·d和CGA 30、60、120 mg/kg·d灌胃10 d，另以C57BL/6小鼠10只设为正常对照组。检测小鼠疾病活动指数(disease activity index，DAI)；以苏木精-伊红(hematoxylin-eosin，HE)染色观察结肠组织病理变化；酶联免疫吸附试验(enzyme linked immunosorbent assay，ELISA)检测结肠组织中肿瘤坏死因子-α(tumor necrosis factor-α，TNF-α)、白细胞介素-6(interleukin-6，IL-6)、IL-10、IL-1β水平；定量实时聚合酶链式反应(quantitative real time-polymerase chain reaction，qRT-PCR)检测结肠组织中诱导型一氧化氮合酶(inducible nitric oxide synthase，iNOS)、精氨酸酶-1(arginase-1，Arg-1)的mRNA表达；免疫印迹检测结肠组织小鼠无翅型乳腺肿瘤病毒整合位点家族成员5a(wingless type 5a，Wnt5a)、C1型尼曼-匹克蛋白(Nieman-Pick type C1，NPC1)的蛋白表达；流式细胞术检测结肠组织M1型及M2型巨噬细胞比例。[结果] 与正常对照组比较，UC模型组DAI评分显著增高，结肠组织出现明显炎症病理改变，M1型巨噬细胞比例，TNF-α、IL-6、IL-1β水平，iNOS mRNA表达，Wnt5a及NPC1蛋白表达均显著增高，M2型巨噬细胞比例、IL-10水平及Arg-1 mRNA表达均显著降低(P<0.01)。与UC模型组比较，CGA可显著降低小鼠DAI评分，减轻结肠组织炎症病理改变，降低结肠组织M1型巨噬细胞比例，TNF-α、IL-6、IL-1β水平，iNOS mRNA表达，以及Wnt5a和NPC1蛋白表达，增加M2型巨噬细胞比例、IL-10水平及Arg-1 mRNA表达(P<0.05，P<0.01)。[结论] CGA可通过减少巨噬细胞向M1型极化，从而减轻由DSS诱导的炎症反应以治疗UC，其机制与抑制Wnt5a/NPC1信号通路活化有关。 |
| 英文摘要: |
| [Objective] To investigate the therapeutic effect and molecular mechanism of chlorogenic acid(CGA) on dextan sodium sulfate(DSS)-induced ulcerative colitis(UC). [Methods] Fifty C57BL/6 mice were intraperitoneally injected with 3%DSS for 7 days to establish the animal model of UC and were randomly divided into 5 groups. Except UC model group， the other 4 groups were separately given sulfasalazine(SZ) 100 mg/kg·d and CGA 30，60，120 mg/kg·d by gavage for 10 days， and 10 C57BL/6 mice were set as normal control group. Disease activity index(DAI) was detected; hematoxylin-eosin(HE) staining was used to observe the pathological changes of colon tissues; the levels of tumor necrosis factor-α(TNF-α)， interleukin-6(IL-6)， interleukin-10(IL-10) and interleukin-1β(IL-1β) in colon tissues were detected by enzyme linked immunosorbent assay(ELISA); the mRNA expressions of inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1) in colon tissues were detected by quantitative real time-polymerase chain reaction(qRT-PCR); the expressions of wingless type mouse mammary tumor virus integration site family type 5a(Wnt5a) and Nieman-Pick type C1(NPC1) in colon tissues were detected by Western blot; the proportion of M1 and M2 macrophages in colon tissues was determined by flow cytometry. [Results] Compared with normal control group， the DAI score of UC model group was significantly increased， and there were obvious inflammatory pathological changes in colon tissue， proportion of M1 macrophages， TNF-α， IL-6， IL-1β levels， iNOS mRNA expression， Wnt5a and NPC1 protein expression were significantly increased， while proportion of M2 macrophages， IL-10 level， and Arg-1 mRNA expression were significantly decreased(P<0.01). Compared with UC model group， CGA significantly decreased DAI score， attenuated inflammatory pathological changes in colon tissue， decreased proportion of M1 macrophages， TNF-α， IL-6， IL-1β levels， iNOS mRNA expression， Wnt5a and NPC1 protein expression， and increased proportion of M2 macrophages， IL-10 level and Arg-1 mRNA expression were observed in colon tissue(P<0.05， P<0.01). [Conclusion] CGA could reduce the inflammatory response induced by DSS to treat UC by reducing macrophage polarization to M1 type， and the mechanism is related to the inhibition of Wnt5a/NPC1 signaling pathway activation. |
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