灰绿黄堇总生物碱对实验性溃疡性结肠炎的作用研究

The effect of alkaloids of corydalis adunca maxim on experiment ulcerative colitis induced by dextran sulfate sodium

目的研究灰绿黄堇总生物碱(ACAM)对小鼠结肠炎的作用及其机制。方法实验设正常、模型、柳氮磺胺吡啶组(SASP,520mg/kg)和ACAM组(100、200、400mg/kg)。正常组小鼠饮用蒸馏水,其余组自由饮用4%葡聚糖硫酸钠(DSS)水溶液,同时分别灌胃给予溶剂或干预药物(0.2ml/10g,1次/d×7d)。记录小鼠疾病活动指数(DAI);测定结肠组织MDA含量,SOD、MPO活性及ICAM-1、NF-κBp65表达水平。结果模型组DAI显著增高,结肠黏膜损伤严重;MDA舍量、MPO活性及ICAM-1和NF-κBp65表达明显升高。SOD活性下降(P<0.01)。SASP520mg/kg能明显逆转上述改变;ACAM100mg具有相似的作用。结论ACAM可能通过抗氧自由基作用,抑制炎性细胞活化、迁移及NF-κB激活,缓解小鼠结肠炎性反应。

Objective To investigate the effect of alkaloids of corydalis adunca maxim（ACAM） on experimental ulcerative colitis in mice. Methods BALB/C mice of 6 groups were allowed to drink either 4% dex- tran sulfate sodium （DSS） solution or distilled water freely with different doses of ACAM （50,100,200 mg/kg） or salicylazosulfapyridine（ SASP,520 mg/kg）, and solvent（0. 2 ml/10 g）once a day for 7 days, respectively. The symptom of ulcerative colitis was evaluated by disease activity index （DAI）, Myeloperoxidase （MPO）and superoxide dismutase（SOD） activities and malondialdehyde（MDA） content were determined by HE staining and im- munohistochemistry of expressions of NF-KB p65 and intercellular adhesion molecule 1 （ ICAM-1 ） proteins to ob- serve the damage of colon tissues and. possible mechanisms. Results DAI, MPO activity, MDA content and expressions of ICAM-1 and NF-KB were markedly increased, while SOD activity decreased in DSS-treated mice. Treatment of different doses of ACAM or SASP in mice decreased significantly DAI, MPO activity and MDA con- tent,improved histological changes of colon tissues, blunted the expressions of NF-KB p65 and ICAM-1 proteins, and promoted SOD activity. Conclusion ACAM has excellent therapeutic effect on ulcerative colitis caused by DSS. The possible mechanism may be related to its antioxidant and anti-inflammatory activities associated with inhibiting the NF-KB activation and ICAM-1 expression.