二氢杨梅素对小鼠葡聚糖硫酸钠结肠炎的干预作用  

Effect of dihydromyricetin on mice with ulcerative colitis induced by dextran sulfate sodium

作　　者：李佩容[1] 危蓉[1] 阎俊[1] 吴志平[1] 齐国卿[1] 谢瑞霞[1] 王小英[1] 张德奎[1] 

机构地区：[1]兰州大学第二医院消化科,甘肃兰州730030

出　　处：《中国新药与临床杂志》2017年第5期268-274,共7页Chinese Journal of New Drugs and Clinical Remedies

基　　金：国家自然科学基金(81272661);甘肃省自然科学基金(1506RJZA204)

摘　　要：目的探讨二氢杨梅素(DMY)对葡聚糖硫酸钠(DSS)诱导的小鼠溃疡性结肠炎(UC)的作用效果。方法将60只Balb/C小鼠随机分为正常对照组、模型组、DMY低剂量组(50 mg·kg^(-1)·d^(-1))、DMY中剂量组(100 mg·kg^(-1)·d^(-1))、DMY高剂量组(200 mg·kg^(-1)·d^(-1))和5-氨基水杨酸组(50 mg·kg^(-1)·d^(-1)),各10只。正常对照组小鼠每日给予蒸馏水饮用,其余组小鼠给予4%DSS连续饮用7 d,诱导小鼠急性UC模型,与此同时给予对应剂量的药物灌胃治疗。7 d后处死小鼠并计算小鼠疾病活动指数(DAI)、光镜下结肠组织损伤评分(TDI),流式细胞法测定外周血中调节性T淋巴细胞(Treg)、辅助性T细胞17(Th17)占CD4+T细胞的百分比,Western blot及免疫组化法测定结肠组织中基质金属蛋白酶9(MMP 9)的表达水平。结果与正常对照组相比,模型组DAI、TDI明显升高(P<0.01),Treg/Th17比值明显降低(P<0.01),MMP 9表达升高(P<0.05)。与模型组相比,DMY低、中、高剂量组小鼠Treg/Th17比值明显升高(P<0.01),MMP 9表达降低(P<0.05),DMY中、高剂量组小鼠DAI、TDI明显降低(P<0.01),且随着治疗剂量增加,升高或降低幅度愈明显。结论 DMY可以显著缓解DSS诱导的小鼠UC炎症,且与剂量呈正相关。AIM To investigate the effect of dihydromyricetin （DMY） on mice with ulcerative colitis（UC） induced by dextran sulfate sodium （DSS）. METHODS Sixty Balb/C mice were divided into six groups randomly, normal control group, model group, DMY low-dose group （50 mg·kg-1·d-1） , DMY middle-dosegroup （100 mg·kg-1·d-1）, DMY high-dose group （200 mg·kg-1·d-1）, and 5-ASA group （50 mg·kg-1·d-1）. The normal control group mice were fed with distilled water, and other groups mice were provided 4%DSS to induce the acute UC models during seven days simultaneously accompanied with a certain amount of drugs gastric gavage treatment. Mice were sacrificed seven days later and the disease activity index （DAI） and tissue damage index （TDI） were calculated, the percentage of T-lymphocytes, regulatory （Treg） and Thl7 cells in CD4＋T cells in peripheral blood were measured by flow cytometry, and Western blot and immunohistochemistry were used to detect the expression level of matrix metalloproteinase 9 （MMP 9） in colonic tissues. RESULTS Compared with the normal control group, the ratio of Treg/Thl7 in the model group was significantly decreased （P 〈 0.01）, while DAI and TDI were significantly increased （P 〈 0.01） , and the expression of MMP 9 was increased （P 〈 0.05）. However, contrasting to the model group, the ratio of Treg/Thl7 in the DMY low-dose group, middle-dose group and high-dose group were significantly increased （P 〈 0.01）, and the expression of MMP 9 were decreased （P 〈 0.05）, while in the DMY middle-dose group and high-dose group, DAI and TDI were significantly decreased （P 〈 0.01）, and with the dose increasing, the Treg/Thl7 increasing or MMP 9 decreasing were more obvious. CONCLUSION DMY can significantly alleviate the inflammation of mice with ulcerative colitis induced by DSS and the effect is positively correlated with the dose.

关 键 词：二氢杨梅素 结肠炎 溃疡性 小鼠 T淋巴细胞 调节性 T淋巴细胞 辅助诱导 

分 类 号：R574.1[医药卫生—消化系统]