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危水香,张歆,王晗,曾玲静,黄凯伦,游玲娜,吴异兰.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[J].湖南中医药大学学报,2024,44(1):16-21[点击复制] |
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| 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 |
| 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) |
| 摘要: |
| 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Western 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。 |
| 关键词: 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 |
| DOI：10.3969/j.issn.1674-070X.2024.01.003 |
| 投稿时间：2023-07-13 |
| 基金项目: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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| Effect of Qinghuachang Drink on mice with colitis-associated colorectal cancer and Intestinal barrier function |
| WEI Shuixiang,ZHANG Xin,WANG Han,ZENG Lingjing,HUANG Kailun,YOU Lingna,WU Yilan |
| (Fujian University of Chinese Medicine, Fuzhou, Fujian 350122, China;Clinical Skills Teaching Center, Fujian University of Chinese Medicine, Fuzhou, Fujian 350122, China;Department of Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, China) |
| Abstract: |
| 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. |
| Key words: Qinghuachang Drink colitis-associated colorectal cancer intestinal barrier Claudin-1 Occludin ZO-1 |
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