清热化湿调枢方对葡聚糖硫酸钠诱导的结肠炎模型小鼠肠黏膜屏障及相关蛋白表达的影响  

Effects of Qingre Huashi Tiaoshu Formula(清热化湿调枢方)on Intestinal Mucosal Barrier and Expression of Related Proteins in Dextran Sodium Sulfate-induced Colitis Model Mice

作　　者：苏晓兰[1] 姚梦茜 陈琳 张涛[1,2] 王琳 卿香丽 张格知[1,2] 魏玮 SU Xiaolan;YAO Mengxi;CHEN Lin;ZHANG Tao;WANG Lin;QING Xiangli;ZHANG Gezhi;WEI Wei(Wangjing Hospital,China Academy of Chinese Medical Sciences,Beijing,100102;China Academy of Chinese Medical Sciences;Chengdu University of Traditional Chinese Medicine)

机构地区：[1]中国中医科学院望京医院,北京市100102 [2]中国中医科学院 [3]成都中医药大学

出　　处：《中医杂志》2022年第16期1566-1572,共7页Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(81973638);中央级公益性科研院所基本科研业务费专项(ZZ13-YQ-035);国家重大疑难疾病中西医临床协作能力建设项目。

摘　　要：目的探讨清热化湿调枢方治疗溃疡性结肠炎的可能作用机制。方法36只C57BL/6小鼠随机抽取6只小鼠为正常组,其余小鼠均给予2.5%葡聚糖硫酸钠(DSS)水溶液自由饮用7天以制备DSS结肠炎小鼠模型。将造模成功小鼠再随机分为模型组,美沙拉嗪组以及清热化湿调枢方低、中、高剂量组,每组6只。正常组和模型组小鼠予0.5 ml纯水灌胃;美沙拉嗪组小鼠给予0.52 g/(kg·d)美沙拉嗪混悬液灌胃;清热化湿调枢方低、中、高剂量组小鼠分别给予清热化湿调枢方0.845、1.690、3.380 g/(kg·d)灌胃;各组均每日1次,连续10天。干预后测量各组小鼠体质量并进行疾病活动指数(DAI)评分,测量结肠长度并观察结肠组织病理变化,检测结肠组织黏蛋白2(MUC-2)阳性表达及带状闭合蛋白1(ZO-1)、闭合蛋白1(Claudin-1)、咬合蛋白(Occludin)表达。结果与正常组相比,模型组和清热化湿调枢方低剂量组小鼠的体质量下降,DAI评分明显升高,结肠长度变短,结肠组织ZO-1、Occludin、Claudin-1蛋白表达均降低(P<0.05)。与模型组和清热化湿调枢方低剂量组比较,美沙拉嗪组和清热化湿调枢方高、中剂量组小鼠体质量增加,DAI评分下降,结肠长度增长,结肠组织ZO-1、Claudin-1、Occludin蛋白表达升高(P<0.05)。正常组小鼠肠黏膜上皮完整,无炎性细胞浸润;模型组小鼠肠黏膜上皮缺损,杯状细胞明显减少,固有层及隐窝结构破坏严重,排列紊乱,并可见大量淋巴细胞浸润;清热化湿调枢方高剂量组和美沙拉嗪组小鼠结肠黏膜上皮几乎无缺损,极少炎性细胞浸润;而清热化湿调枢方中、低剂量组改善不明显。正常组MUC-2表达为棕黄色颗粒,广泛分布在杯状细胞胞浆(核周及核膜);模型组小鼠结肠组织中MUC-2阳性表达明显减少;美沙拉嗪组和清热化湿调枢方高、中剂量组MUC-2阳性表达较模型组有较明显的恢复。结论高、中剂量清热化湿调枢方对DSS结Objective To explore the possible mechanism of Qingre Huashi Tiaoshu Formula(清热化湿调枢方,QHTF)in the treatment of ulcerative colitis(UC).Methods Thirty-six C57BL/6 male mice were included,of which six mice were randomly selected as normal group,and the rest were given 2.5%dextran sodium sulfate(DSS)aqueous solution for 7 days to prepare DSS-induced colitis mice.The successfully modeled mice were randomly divided into five groups,namely the model group,mesalazine group,and the low-,medium-and high-dose QHTF groups,with six mice in each group.Then the normal group and the model group were given 0.5 ml of pure water by gavage;mice in the mesalazine group were given 0.52 g(/kg·d)of mesalazine suspension by gavage;mice in the low-,medium-and high-dose QHTF groups were given 0.845,1.69,and 3.38 g(/kg·d)of QHTF suspension by gavage.All groups were intervented once a day for 10 consecutive days.After intervention,the body weight,disease activity index(DAI),colon length,colon histopathological results were observed,and the positive expression of colonic tissue mucin 2(MUC-2)and the expression of occludin 1(ZO-1),claudin 1(Claudin-1)and occludin(Occludin)were detected.Results Compared to those of mice in the normal group,the body weight of mice in the model group and low-dose QHTF group decreased,and the DAI score increased,while colon length was shortened,and the expression of ZO-1,Occludin,and Claudin-1 in the colonic tissue decreased(P<0.05).Compared to the model group and low-dose QHTF group,the other three groups had increased body weight,decreased DAI,longer colon length,and increased expression of ZO-1,Occludin,and Claudin-1(P<0.05).In the normal group,the intestinal mucosal epithelium of the mice was intact with no inflammatory cell infiltration,while in the model group,the intestinal mucosal epithelium was defective with significantly reduced goblet cells,severely damaged and disorderly arranged lamina propria and crypts structure,and a large number of infiltrated lymphocytes;in the high-dose QHTF grou

关 键 词：溃疡性结肠炎 清热化湿调枢方 结肠组织 肠黏膜屏障 黏蛋白 紧密连接蛋白 

分 类 号：R285.5[医药卫生—中药学]