实验性结肠炎中一氧化氮的变化及其在体内和体外受褪黑素的抑制作用
Change of nitric oxide in experimental colitis and its inhibition by melatonin in vivo and in vitro.
作者信息
Mei Q, Xu J-M, Xiang L, Hu Y-M, Hu X-P, Xu Z-W
机构信息
Digestive Department, The First Affiliated Hospital, Anhui Medical University, Hefei, China.
出版信息
Postgrad Med J. 2005 Oct;81(960):667-72. doi: 10.1136/pgmj.2004.030817.
AIM
To investigate the change of nitric oxide (NO) in rat colitis and its inhibition by melatonin in vivo and in vitro.
METHODS
In vivo, rat colitis was established intracolonically with trinitrobenzenesulphonic acid (TNBS) and ethanol. The animals were randomised into five groups: control group, model group, melatonin group (2.5, 5.0, 10.0 mg/kg), and treated intracolonically with saline, saline and melatonin respectively (once a day, from day 7 after colitis was established to day 28). After the end of the experiment, the mucosal damage index (CMDI) and histology score (HS) were evaluated and the level of myeloperoxidase (MPO) and malondiadehyde (MDA) and NO in the colon tissue were measured. In vitro, the co-culture model of the inflamed colon mucosa (from the colitis) with lipopolysaccharide (LPS), and the colonocytes oxidative injury model by hydroxyl radical, were designed respectively to elucidate the inhibition of NO by melatonin.
RESULTS
After treated with TNBS/ethanol, the extent of CMDI and HS, the levels of MPO, MDA, and NO in the model group, were higher than that in the control group; melatonin ameliorated these parameters effectively. The stimulation of LPS increased the level of NO and MPO and MDA in the co-culture model of inflamed colon mucosa, and melatonin significantly reduced the level of MPO, MDA, and NO. In the coloncyte oxidative injury model by hydroxyl radical, the contents of LDH, MDA, and NO were increased; melatonin reversed this oxidative injury considerably.
CONCLUSION
This study showed that TNBS/ethanol induced colitis was pharmacologically controlled by melatonin in vivo and in vitro.
目的
研究大鼠结肠炎中一氧化氮（NO）的变化以及褪黑素在体内和体外对其的抑制作用。
方法
在体内，用三硝基苯磺酸（TNBS）和乙醇经结肠内注射建立大鼠结肠炎模型。将动物随机分为五组：对照组、模型组、褪黑素组（2.5、5.0、10.0 mg/kg），分别经结肠内注射生理盐水、生理盐水和褪黑素（每天一次，从结肠炎模型建立后第7天至第28天）。实验结束后，评估黏膜损伤指数（CMDI）和组织学评分（HS），并检测结肠组织中髓过氧化物酶（MPO）、丙二醛（MDA）和NO的水平。在体外，分别设计炎症结肠黏膜（来自结肠炎模型）与脂多糖（LPS）的共培养模型以及羟基自由基诱导的结肠上皮细胞氧化损伤模型，以阐明褪黑素对NO的抑制作用。
结果
TNBS/乙醇处理后，模型组的CMDI和HS程度、MPO、MDA和NO水平均高于对照组；褪黑素有效改善了这些参数。LPS刺激增加了炎症结肠黏膜共培养模型中NO、MPO和MDA的水平，而褪黑素显著降低了MPO、MDA和NO的水平。在羟基自由基诱导的结肠上皮细胞氧化损伤模型中，乳酸脱氢酶（LDH）、MDA和NO的含量增加；褪黑素显著逆转了这种氧化损伤。
结论
本研究表明，TNBS/乙醇诱导的结肠炎在体内和体外均可被褪黑素药物性控制。
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