2018 年第 4 期 第 13 卷

阿卡宁治疗炎症性肠病模型小鼠的实验研究

Experimental study of alkannin treating mouse model with inflammatory bowel disease

作者：杨厚涞孙华文王秋爽王琦

英文作者：

单位：430060武汉大学人民医院胃肠外一科

英文单位：

关键词：炎症性肠病；阿卡宁；转化生长因子β1；白细胞介素17

英文关键词：

• 摘要：

• 目的    探讨阿卡宁在炎症性肠病模型小鼠急性炎症中的治疗作用及可能机制。方法    选取64只6～8周龄雌性无特定病原体级Bal/c小鼠完全随机分为8组，每组8只。正常对照组给予充足的食物和水，每天给予1 ml食用橄榄油灌胃；模型组给予充足的食物、3%葡聚糖硫酸钠（DSS）灭菌水溶液，每天给予1 ml食用橄榄油灌胃；1 mg/kg阿卡宁（AKN-1）组、2 mg/kg阿卡宁（AKN-2）组、4 mg/kg阿卡宁（AKN-4）组、8 mg/kg阿卡宁（AKN-8）组、16 mg/kg阿卡宁（AKN-16）组分别给予充足的食物、3%DSS灭菌水溶液，每天给予1 ml溶解相应剂量阿卡宁的食用橄榄油灌胃；阳性对照组给予充足的食物、3%DSS灭菌水溶液，每天给予1 ml溶解美沙拉嗪的食用橄榄油灌胃。每天给药1次，连续6 d。比较各组小鼠结肠大体形态损伤指数评分(CMDI)、结肠病理组织学评分（TDI）和转化生长因子β1（TGF-β1）、白细胞介素17（IL-17）的mRNA和蛋白表达水平。结果    AKN-1组及AKN-2组CMDI及TDI与模型组比较，差异无统计学意义（均P＞0.05）。AKN-4组、AKN-8组、AKN-16组CMDI及TDI均明显低于模型组（均P＜0.05）。AKN-1组、AKN-2组、AKN-4组、AKN-8组、AKN-16组的TGF-β1、IL-17 mRNA表达水平均明显低于模型组［TGF-β1 mRNA：（2.90±0.33）、（2.71±0.73）、（2.14±0.19）、（2.06±0.35）、（1.63±0.31）比（3.88±0.58）；IL-17 mRNA：（2.48±0.35）、（2.25±0.64）、（2.07±0.21）、（1.78±0.24）、（1.67±0.23）比（3.21±0.41）］（均P＜0.05）。AKN-1组、AKN-2组、AKN-4组、AKN-8组、AKN-16组的TGF-β1、IL-17蛋白表达水平均明显低于模型组（均P＜0.05）。结论    阿卡宁可以作用于TGF-β1—辅助性T细胞17—IL-17轴，发挥抗炎效果，对炎症性肠病有一定的治疗作用。

• Objective    To investigate the therapeutic effect and possible mechanisms of alkannin on inflammatory bowel disease in mice. Methods    Sixty-four specific-pathogen-free female Bal/c mice were randomly divided into 8 groups, with 8 mice in each group. The normal control group was given food, water, and 1 ml edible olive oil. The model group was given food, 3% dextran sodium sulfate（DSS） sterile aqueous solution and 1 ml edible olive oil. The 1 mg/kg alkannin（AKN-1） group, 2 mg/kg alkannin（AKN-2） group, 4 mg/kg alkannin（AKN-4） group, 8 mg/kg alkannin（AKN-8） group, 16 mg/kg alkannin（AKN-16） group were given food, 3% DSS sterile aqueous solution and 1 ml edible olive oil dissolved with alkannin. The positive control group was given food, 3% DSS sterile aqueous solution and 1 ml edible olive oil dissolved with mesalazine. After 6 days of treatment, colon macroscopic damage index(CMDI), tissue damage index(TDI) were used to evaluate the therapeutic effect. Expression levels of transforming growth factor-β1(TGF-β1) and interleukin-17(IL-17) mRNA and protein were tested. Results   There were no significant differences of CMDI and TDI scores among AKN-1 group, AKN-2 group and model group(P＞0.05). CMDI and TDI scores in AKN-4 group, AKN-8 group and AKN-16 group were significantly lower than those in model group(P＜0.05). Expression levels of TGF-β1 mRNA and IL-17 mRNA in AKN-1, AKN-2, AKN-4, AKN-8 and AKN-16 groups were significantly lower than those in model group［TGF-β1 mRNA： （2.90±0.33）,（2.71±0.73）,（2.14±0.19）,（2.06±0.35）,（1.63±0.31） vs （3.88±0.58）； IL-17 mRNA： （2.48±0.35）,（2.25±0.64）,（2.07±0.21）,（1.78±0.24）,（1.67±0.23） vs （3.21±0.41）］(P＜0.05). Expression levels of TGF-β1 and IL-17 in AKN-1, AKN-2, AKN-4, AKN-8 and AKN-16 groups were significantly lower than those in model group(P＜0.05). Conclusion    Alkannin can change the TGF-β1-helper T cell 17-IL-17 axis to exert anti-inflammatory effect on inflammatory bowel disease in mice.