褪黑激素调节巨噬细胞功能减轻结肠免疫损伤

目的:研究褪黑素(MT)对大鼠结肠免疫损伤的影响及与巨噬细胞功能的关系.方法:利用2,4,6-三硝基苯磺酸(TNBS)和乙醇灌肠制备大鼠结肠炎模型.实验设正常对照组、模型对照组、5-氨基水杨酸给药组(100 mg/kg)和MT给药组(2.5,5.0,10.0 mg/kg),每大灌肠给药一次,从制备模型d 7开始共21 d.测定结肠粘膜损伤指数(CMDI)、粘膜病理组织学评分(HS)、粪便隐血实验(OBT)和髓过氧化物酶(MPO)、IL-1、TNF-α、NO水平.结果:大鼠经TNBS和乙醇处理后CMDI、HS、OBT和MPO水平以及结肠和血浆中IL-1、TNF-α和NO水平明显高于正常,MT可不同程度逆转上述变化,减轻大鼠结肠免疫损伤.结论:MT灌肠能减轻结肠炎大鼠粘膜损伤,此与MT调节巨噬细胞功能有关.

Melatonin reduces colon immunological injury in rats by regulating activity of macrophages

AIM: To investigate the effects of melatonin on the colon immunological injury of rats and the role of macrophages in this process. METHODS: The rats colitis was established by intrarectal injection with 2,4,6-trinitrobenzenesulfonic acid (TNBS) and ethanol. The animals were randomized into 6 groups: normal group, model group, 5-aminosalicylic acid group (100 mg/kg), and melatonin group (2.5, 5.0, and 10.0 mg/kg), treated intrarectally with saline, saline, 5-aminosalicylic acid, and melatonin, respectively (once a day, from d 7 after colitis established to d 28). At the end of the experiment, the colon mucosa damage index (CMDI), the score of histology (HS), the level of myeloperoxidase(MPO), and the sore of occult blood test (OBT) were evaluated. Meanwhile, the activity of interleukin-1 (IL-1), tumour necrosis factor-alpha (TNF-alpha, and nitric oxide (NO) were also detected. RESULTS: After treated with TNBS and ethanol, the extents of CMDI, HS, OBT, and the level of MPO in model group were more higher than that in normal group. Melatonin could alleviate the colon injury, and reduce the level of MPO and the degree of OBT. The activity of IL-1, TNF-alpha, and NO which released mainly from macrophages was elevated remarkably. Melatonin could depress all this parameters. CONCLUSION: Melatonin could reduce the colon damage in the colitis rats by regulating macrophage activity.