甘草酸二铵抗大鼠溃疡性结肠炎作用及相关机制研究  

Effects of diammonium glycyrrhizinate on ulcerative colitis in rats and the underlying mechanism

作　　者：刘颖[1] 王莹[1] 齐正[1] 丁虹[1] 

机构地区：[1]武汉大学药学院,武汉430072

出　　处：《中国新药杂志》2007年第24期2027-2031,共5页Chinese Journal of New Drugs

摘　　要：目的:研究甘草酸二铵(DG)对2,4,6-三硝基苯磺酸(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(SASP,225 mg.kg-1)为阳性对照,研究甘草酸二铵结肠给药(2,10,50 mg.kg-1,qd,共给药7 d)对TNBS性溃疡性结肠炎大鼠的结肠单位长度重量、结肠黏膜损伤评分、髓过氧化物酶(MPO)、结肠组织丙二醛(MDA)和超氧化物歧化酶(SOD)以及血清白介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)含量的影响;由HE染色、扫描和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环氧酶-2(COX-2)和细胞间黏附分子-1(ICAM-Ⅰ)表达的变化。结果:模型动物结肠组织发生明显病理学变化,伴有充血、溃疡以及大量的炎性细胞浸润,DG组均不同程度改善结肠组织病理学变化,降低单位长度结肠重量,并呈剂量依赖关系。与正常组比较,模型组大鼠结肠组织中MPO活性和MDA含量显著升高,SOD活性明显下降;DG能显著逆转模型组MPO,MDA和SOD的变化。与模型组比较,DG组结肠组织COX-2和ICAM-Ⅰ表达下调,血清中IL-1β和TNF-α表达量也有不同程度下降。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、降低促炎性细胞因子水平等有关。Objective：To determine the effect of diammonium glycyrrhizinate （DG） and possible mechanism on ulcerative colitis （UC） induced by trinitrobenzene sulfonic acid （TNBS） in rats. Methods ： UC was induced by TNBS and ethanol in Wistar rats. After DG （2, 10 and 50 mg· kg^-1 ） was given into the colon for 7 days, the colon mucosa damage index and histopathological score were determined, levels of MPO, MDA and .SOD were measured by ultra violent spectrophotometry, and interleukin-1 （IL-1β） and tumor necrosis factor-α （TNF-α） in serum were detected by radiation immunization. The expression of COX-2 and ICAM- I was detected by immunohistochemical staining, and pathological changes in colon were observed by light microscopy after HE staining and by electromicroscopy. Results： The colonic mucosa of UC rats showed hyperemia, ulcers and infiltrated inflammatory cells. DG dose-dependently attenuated the severity of gross lesions and reduced the histopathological scores. MPO activity and MDA concentration in colon, and IL-1β and TNF-α in serum were significantly increased; SOD activity was reduced in UC rats. DG attenuated these changes, and also reduced the expression of COX-2 and ICAM- I in UC colon. Conclusion： Colon administration of DG exerts a protective effect on colon injury in TNBS-induced UC rats, which may be due to anti-oxidation and inhibition of inflammatory cytokines.

关 键 词：溃疡性结肠炎 甘草酸二铵 抗氧化 细胞因子 结肠给药 

分 类 号：R965.1[医药卫生—药理学] R975.6[医药卫生—药学]