清化肠饮对结肠炎相关结直肠癌小鼠及其肠道屏障功能的影响OACSTPCD
Effect of Qinghuachang Drink on mice with colitis-associated colorectal cancer and Intestinal barrier function
目的 观察清化肠饮对结肠炎相关结直肠癌(colitis-associated colorectal cancer,CAC)小鼠及其肠道屏障功能的影响.方法 将40只C57BL/6小鼠随机均分为空白组、模型组、清化肠饮组、阳性对照组.除空白组外,其余组均用氧化偶氮甲烷(azoxy-methane,AOM)/葡聚糖硫酸钠(dextran sulfate sodium salt,DSS)联合诱导建立CAC小鼠模型,清化肠饮组给予清化肠饮灌胃剂量为1.8 g/(kg·d);阳性对照组给予柳氮磺吡啶混悬液0.45 g/(kg·d);空白组给予等量无菌生理盐水灌胃.均干预8周.观察并记录小鼠一般情况、体质量、疾病活动指数(disease activity index,DAI)及肿瘤长度;采用HE染色法观察小鼠结直肠组织病理变化;采用West-ern blot法检测小鼠结直肠组织中闭合蛋白-1(Claudin-1)、咬合蛋白(Occludin)、带状闭合蛋白-1(ZO-1)蛋白表达水平.结果 模型组出现便血、脱肛等情况.与空白组相比,模型组、清化肠饮组、阳性对照组小鼠DAI评分明显升高(P<0.05或P<0.01).与空白组相比,模型组、清化肠饮组、阳性对照组小鼠结直肠长度均缩短(P<0.01或P<0.05);与模型组比较,清化肠饮组与阳性对照组结直肠长度增长(P<0.01).HE病理结果显示,模型组腺体高级别管状腺瘤形成,清化肠饮组存在低级别腺瘤和高级别瘤变.与空白组相比,模型组小鼠结直肠肿瘤组织中Claudin-1蛋白表达升高(P<0.01),Occludin、ZO-1蛋白表达水平降低(P<0.01);与模型组相比,清化肠饮组、阳性对照组Claudin-1蛋白表达水平降低(P<0.01),清化肠饮组、阳性对照组Occludin、ZO-1蛋白表达水平升高(P<0.05或P<0.01).与清化肠饮组相比,阳性对照组Claudin-1蛋白表达水平降低(P<0.01),Occludin、ZO-1蛋白表达水平升高(P<0.01).结论 清化肠饮可抑制CAC,其机制可能与改善肠道炎症反应、调节肠道屏障功能相关.
Objective To observe the effects of Qinghuachang Drink(QHCD)on the mouse model of colitis-associated colorectal cancer(CAC)and its intestinal barrier function.Methods Forty C57BL/6 mice were randomized into blank group,model group,QHCD group,and positive control group.Except for blank group,the rest groups were induced to establish a CAC model by azoxymethane(AOM)/dextran sulfate sodium salt(DSS).QHCD,positive control,and blank groups were given QHCD 1.8 g/(kg·d),sulfasalazine suspension 0.45 g/(kg·d),and the equal volume of sterile saline by gavage,respectively,for 14 d in succession.The general condition,body mass and disease activity index(DAI)of mice were observed and recorded;HE staining was used to observe the pathological changes in the colorectal tissue of mice;Western blot was used to determine the protein expression levels of Claudin-1,Occludin,ZO-1 in the colorectal tissue.Results The mice of model group had bloody stool and rectal prolapse.After intervention,the condition of mice in QHCD group was improved and the DAI score decreased(P<0.05 or P<0.01).The pathological results of HE showed that high-grade tubular adenomas formed in model group,and low-grade adenomas and high-grade neoplasia were present in QHCD group,indicating that QHCD could alleviate intestinal inflammation and delay the progression of canceration.Compared with blank group,the protein expression level of Claudin-1 in the colorectal tissue of mice in model group was higher(P<0.01),while the protein expression levels of Occludin and ZO-1 were lower(P<0.01);compared with model group,the protein expression level of Claudin-1 in the colorectal tissue of mice in both QHCD and positive control groups decreased(P<0.01),while the protein expression levels of Occludin and ZO-1 increased(P<0.05).Conclusion QHCD can inhibit CAC,and the mechanism may be related to alleviating intestinal inflammatory response and regulating intestinal barrier function.
危水香;张歆;王晗;曾玲静;黄凯伦;游玲娜;吴异兰
福建中医药大学,福建 福州 350122福建中医药大学临床技能教学中心,福建 福州 350122福建医科大学附属协和医院肿瘤内科,福建 福州 350001
中医学
清化肠饮结肠炎相关结直肠癌肠道屏障闭合蛋白-1咬合蛋白带状闭合蛋白-1
Qinghuachang Drinkcolitis-associated colorectal cancerintestinal barrierClaudin-1OccludinZO-1
《湖南中医药大学学报》 2024 (001)
16-21 / 6
福建省自然科学基金项目(2023J01337);福建中医药大学护理学院专项课题(XHL2022004).
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