基于STAT-3/NF-κB/ICAM-1通路探讨丹皮酚缓解小鼠结肠炎相关性结直肠癌的作用机制
Mechanism of Action of Paeonol in Alleviating Colitis-related Colorectal Cancer in Mice: An Analysis Based on the STAT-3/NF-κB/ ICAM-1 Pathway
  
DOI:
中文关键词:  丹皮酚  结肠炎  直肠癌  炎—癌转化  STAT-3  NF-κB  ICAM-1
英文关键词:Paeonol  Colitis  Rectal cancer  Colitis-cancer transformation  Signal transducer and activator of transduction 3  Nuclear factor κB  Intercellular adhesion molecule 1
基金项目:安徽省自然科学基金项目(2008085MH300)
作者单位
刘 博,张传凤,马克龙,汪长中,颜贵明 安徽中医药大学安徽 合肥 230012 
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中文摘要:
      目的 从STAT-3/NF-κB/ICAM-1信号通路探讨丹皮酚缓解小鼠结肠“炎—癌转化”的机制。方法 构建结肠“炎—癌转化”小鼠模型,ELISA法检测小鼠血清肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素6(interleukin-6,IL-6)、白细胞介素1β(interleukin-1β,IL-1β)和白细胞介素10(interleukin-10,IL-10)水平,Western blot法和免疫组织化学染色法检测小鼠结肠组织内信号转导及转录激活因子3(signal transdncers and activators of transduction-3,STAT-3)、核因子-κB(nuclear factor κB,NF-κB)p65和细胞间黏附分子1(intercellular adhesion molecule-1,ICAM-1)蛋白表达水平。结果 光学显微镜下可见丹皮酚治疗组小鼠结肠的炎症细胞浸润、腺体紊乱等病变明显减轻。丹皮酚可显著降低肿瘤数量、肿瘤质量及脾脏指数(P<0.05),显著降低模型小鼠血清TNF-α、IL-6、IL-1β水平(P<0.05),显著升高血清IL-10水平(P<0.05),显著降低小鼠结肠STAT-3、NF-κB p65和ICAM-1的表达水平(P<0.05),其中以丹皮酚中剂量组的作用为优(P<0.05)。结论 丹皮酚能有效缓解小鼠溃疡性结肠炎的炎症反应,其作用机制与调节STAT-3/NF-κB/ICAM-1信号通路有关。
英文摘要:
      Objective To investigate the mechanism of action of paeonol in alleviating colitis-cancer transformation in mice based on the STAT-3/NF-κB/ICAM-1 signaling pathway. Methods A mouse model of colitis-cancer transformation was established. ELISA was used to measure the serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and interleukin-10 (IL-10); Western blot and immunohistochemical staining were used to measure the protein expression levels of signal transducer and activator of transduction 3 (STAT-3), nuclear factor κB (NF-κB) p65, and intercellular adhesion molecule 1 (ICAM-1) in colon tissue. Results The paeonol treatment group had significant alleviation of inflammatory cell infiltration and gland disorder in the colon under a light microscope. Paeonol significantly reduced the number of tumors, tumor mass, spleen index, and the serum levels of TNF-α, IL-6, and IL-1β (P<0.05), significantly increased the serum level of IL-10 (P<0.05), and significantly reduced the expression levels of STAT-3, NF-κB p65, and ICAM-1 in the colon (P<0.05), and middle-dose paeonol had the best effect (P<0.05). Conclusion Paeonol can effectively alleviate inflammatory response in mice with ulcerative colitis, possibly by regulating the STAT-3/NF-κB/ICAM-1 signaling pathway.
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