四君子汤对溃疡性结肠炎小鼠模型肠黏膜屏障的作用机制  

Mechanism underlying effect of Sijunzi decoction on intestinal mucosal barrier of mice with ulcerative colitis

作　　者：黄婧渝 农辉[1] 裴羡 黄雪[1] 谭至柔[2] 覃蒙斌[2] 李卉[3] 张钰琴[4] 

机构地区：[1]广西医科大学第一附属医院老年病学消化内科,广西壮族自治区南宁市530021 [2]广西医科大学第一附属医院消化内科,广西壮族自治区南宁市530021 [3]广西医科大学第一附属医院药剂科,广西壮族自治区南宁市530021 [4]广西医科大学第一附属医院中医科,广西壮族自治区南宁市530021

出　　处：《世界华人消化杂志》2015年第27期4326-4334,共9页World Chinese Journal of Digestology

基　　金：广西中医药民族医药自筹经费科研课题资助项目;No.GZZC14-53~~

摘　　要：目的:探讨四君子汤对溃疡性结肠炎(ulcerative colitis,UC)小鼠模型肠黏膜屏障的作用机制.方法:50只♂BALB/c小鼠,体质量18-20 g,随机分为正常组、模型组、四君子汤低剂量组(2.25 g/kg)、中剂量组(4.50 g/kg)、高剂量组(9.01 g/kg).正常组自由饮用蒸馏水,其余4组给予3%葡聚糖硫酸钠(dextran sulphate sodium,DSS)溶液7 d诱导建立UC模型.第8天起,正常组、模型组予蒸馏水灌胃,四君子汤各组按不同剂量四君子汤灌胃,每天进行疾病活动指数(disease active index,DAI)评分.第15天处死小鼠,ELISA法测量血浆中D-乳酸水平,免疫组织化学法检测结肠黏膜occludin蛋白的表达.结果:与正常组相比,模型组、四君子汤各组D A I评分和结肠组织病理评分升高(P<0.01),而四君子汤中、高剂量组DAI评分和结肠组织病理评分较模型组下降(P<0.01).模型组结肠黏膜充血糜烂,而四君子汤能改善结肠黏膜损伤.模型组血浆D-乳酸含量明显增加,四君子汤各组较模型组减少.免疫组织化学结果提示模型组occludin蛋白表达较正常组减少,四君子汤中、高剂量组较模型组表达增多.四君子汤低剂量组DAI评分、结肠组织病理评分、occludin蛋白与模型组比较差异无统计学意义.结论:四君子汤可以改善DSS诱导的UC小鼠的临床表现、镜下表现,同时降低血浆D-乳酸含量、增加肠黏膜occludin蛋白的表达,其作用机制可能与改善肠黏膜屏障的通透性、保护肠黏膜屏障有关.AIM：To investigate the effect of Sijunzi decoction（SJZD） on the intestinal mucosal barrier of mice with dextran sulphate sodium（DSS）-induced ulcerative colitis and the underlying mechanism.METHODS：Fifty male BALB/c mice were randomly divided into five groups,including a normal group,a DSS group,and low-,medium- and high-dosage SJZD groups.Except the normal group,the other four groups were given distilled water containing3%DSS for 7 d to induce experimental colitis.From day 8 to day14,the normal group and DSS group were given distilled water（0.3mL/d） by gavage,and the three SJZD groups were treated with different dosages of SJZD（2.25,4.50 and 9.01 g/kg,respectively）.Disease active index（DAI） scores were calculated.On day 15,plasma and colon tissue samples were taken from mice to measure levels of plasma D-lactate by ELISA,and expression of occludin by immunohistochemistry,respectively.RESULTS：Compared with the normal group,the DAI and histological scores were significantly elevated in the DSS group and the three SJZD groups（P〈0.01）.However,DAI and histologic scores were significantly decreased in the medium- and high-dosage SJZD groups when compared with the DSS group（P〈0.01）.DSS-induced murine colitis showed ulcer,hyperemia,interstitial edema,and infiltration of inflammatory cells.Different dosages of SJZD significantly reduced histopathological injury.Plasma D-lactate was significantly increased in the DSS group,but was decreased in the three SJZD groups compared with the DSS group.Compared with the DSS group,the expression of occludin in the medium- and high-dosage SJZD groups was improved;the mean density of occludin was significantly lower in the DSS group than in the normal group,but was significantly increased in the medium- and high-dosage groups compared with the DSS group.There were no significant differences in DAI,histological score or the expression of occludin between the DSS group and the low-dosage SJZD group.CONCLUSION：SJZD can ameliorate the clinical manife

关 键 词：四君子汤 溃疡性结肠炎 肠黏膜屏障 D-乳酸 OCCLUDIN蛋白 

分 类 号：R285.5[医药卫生—中药学] R-332[医药卫生—中医学]