复方甘草酸苷对小鼠实验性结肠炎NF-κB、STAT3信号转导通路的影响

Influence of Compound Glycyrrhizin on NF-κB and STAT3 Signal Transduction Pathway in Murine Experimental Colitis

背景:溃疡性结肠炎(UC)的病因、发病机制不明,且缺乏有效治愈手段。对相关信号转导通路的研究有助于了解药物干预的作用机制。目的:观察复方甘草酸苷对小鼠实验性结肠炎的治疗作用及其对NF-κB、STAT3信号转导通路的影响。方法:40只健康昆明小鼠随机分为四组,一组为正常对照组,另三组以噁唑酮诱导实验性结肠炎,随后分别腹腔注射0.9%NaCl溶液(模型对照组)、复方甘草酸苷(甘草酸苷组)或予柳氮磺砒啶(SASP)灌胃(SASP组)7 d。观察各组小鼠疾病活动指数(DAI)、结肠组织大体和组织学损伤评分以及髓过氧化物酶(MPO)活性,蛋白质印记法检测结肠黏膜NF-κB、STAT3活化水平。结果:模型对照组DAI、大体和组织学损伤评分、MPO活性以及结肠黏膜固有层单个核细胞中活化NF-κB p65、STAT3的表达均显著高于正常对照组(P<0.05),甘草酸苷组和SASP组则较模型对照组显著降低(P<0.05),甘草酸苷组与SASP组间仅DAI和组织学损伤评分有显著差异(P<0.05)。结论:复方甘草酸苷能有效改善小鼠实验性结肠炎的炎症活动水平,其作用机制可能与下调NF-κB、STAT3信号转导通路有关。

Background： The etiology and pathogenesis of ulcerative colitis （UC） is not yet clear and is still lack of effective therapeutic approaches. Studies on related signal transduction pathway might be helpful for understanding the mechanism of drug intervention. Aims： To investigate the therapeutic effect of Compound Glycyrrhizin on murine experimental colitis and its influence on NF-κB and STAT3 signal transduction pathway. Methods： Forty healthy Kunming mice were randomly allocated into 4 groups. Ten mice served as normal controls, and the others were treated with oxazolone to induce experimental colitis and then each ten mice received intraperitoneal injection of normal saline （colitis-control group）, Compound Glycyrrhizin （Glycyrrhizin group） or intragastric administration of salicylazosulfapyridine （SASP group）, respectively for 7 days. Mice in each group were assessed with disease activity index （DAI）, scores of macroscopic and microscopic injury and activity of myeloperoxidase （MPO） in colonic tissue. Activation of NF-κB and STAT3 in colonic mucosa was assessed by Western blotting. Results： DAI, scores of macroscopic and microscopic injury and MPO activity, as well as expressions of activated NF-κB p65 and STAT3 in lamina propria mononuclear cells were significantly increased in colitis-control group when compared with those in normal control group （P〈0.05）. In Glycyrrhizin group and SASP group, all the abovementioned indices were decreased when compared with the colitis-control group （P〈0.05）. Only DAI and score of microscopic injury showed significant differences between Glycyrrhizin group and SASP group （P〈0.05）. Conclusions： Compound Glycyrrhizin can ameliorate the inflammatory activity of murine experimental colitis, probably by downregulating the NF-κB and STAT3 signal transduction pathway.