甘草酸二铵抗大鼠溃疡性结肠炎作用及相关机制研究.docVIP

甘草酸二铵抗大鼠溃疡性结肠炎作用及相关机制研究 刘颖，王莹，祝青，奇正，丁虹*（武汉大学药学院，武汉 430072） [摘要] 目的 研究甘草酸二铵对TNBS诱导的大鼠溃疡性结肠炎的作用及可能作用途径。方法 以柳氮磺吡啶为对照研究甘草酸二铵对TNBS性溃疡性结肠炎大鼠的体重、结肠单位重量及结肠粘膜损伤，结肠组织MDA、MPO和SOD的影响；由HE染色，扫描、透射电镜观察结肠组织病理学变化；由免疫组化观察结肠组织IL-10、COX-2、ICAM-Ⅰ的变化。结果 与模型组相比，甘草酸二铵给药各组，均能不同程度改善结肠组织病理学变化，降低肠系数，并呈剂量依赖关系；与正常组相比，模型组大鼠结肠组织中MDA含量、MOP活性显著升高，SOD活性明显下降，甘草酸二铵可逆转上述变化；甘草酸二铵组中结肠组织IL-10表达下调，COX-2、ICAM-Ⅰ表达下调。其中以DG灌肠组中、高剂量效果最好。结论：甘草酸二铵能有效改善溃疡性结肠炎大鼠的结肠炎症反应，其作用机制与抗氧化、诱导抗炎细胞因子IL-10，降低COX-2、ICAM-1的表达有关。 关键词：溃疡性结肠炎；甘草酸二铵；抗氧化；细胞因子；灌肠 Effects of Diammonium Glycyrrhizinate in Ulcerative Colitis in rat and Its Underlying Mechanism LIU Ying , WANG Ying , ZHU Qing , QI Zheng , DING Hong*（College of Pharmaceutical Sciences , Wuhan University , Wuhan 430072 , China） ABSTRACT : OBJECTIVE To determine the effect and possible mechanism of Diammonium Glycyrrhizinate?(DG) on Ulcerative Colitis (UC) induced by trinitrobenzene sulfonic acid - ethanol (TNBS) in rat. METHODS Wistar rats with UC induced by TNBS , weight , colon mucosa damage index and histopathological score , assay of MPO , SOD and MDA by ultra violent spectrophotometry , detection of interleukin-1β (IL-1β) , interleukin-6 (IL-6) and tumer necrosis factor-α (TNF-α) by radiation immunization , expression of IL-10 , COX-2 and ICAM-Ⅰby immunohistochemical staining , were carried out to observe changes of colon ; HE staining , SEM and TEM of colon to study pathological changes. RESULTS Compared with the model group , rats in each DG group recovered with different degree. Their colon mucosa damage index and histopathological score were lower and dose-dependent ; Compared with control group , MDA , MPO and COX-2 , ICAM-Ⅰwere higher ,while SOD , IL-10 was lower , distinctly , which could be reversed by DG. DGM and DGG group were better among all groups. CONCLUSION Administration of DG intracolonically had protective effect on the colon injury in the rat model of colitis induced by TNBS, which was probably due to antioxidation , inhibition of inflammatory