芪附理中灌肠方对溃疡性结肠炎大鼠模型肠黏膜紧密连接功能的调节作用。
Efficacy of Qifu Lizhong enema prescription on intestinal mucosal tight junction function modulation of ulcerative colitis rat model.
机构信息
Clinical Medical college, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China.
Basic Medical college, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China.
出版信息
J Tradit Chin Med. 2023 Apr;43(2):303-311. doi: 10.19852/j.cnki.jtcm.20220922.002.
OBJECTIVE
To investigate the efficacy and mechanism of Qifu Lizhong enema prescription(, QFLZ) on intervening ulcerative colitis (UC) rat model with TCM spleen and kidney insufficiency syndrome.
METHODS
Seventy-two male Sprague-Dawley rats were randomly assigned to six groups: normal model, mesalazine, and QFLZ high, medium, and low dose groups, each with 12 rats. After 3 d of adaptation feeding, all groups except the normal group were induced using rhubarb decoction in combination with trinitrobenzene sulfonic acid (TNBS)/55 % ethanol to establish a UC rat model. Following successful modeling, the normal and model groups received daily saline enema, while the Chinese medicine and Western medicine groups received daily QFLZ and Mesalazine enema for 2 weeks respectively. The disease activity index score, hematoxylin and eosin staining, immunohistochemistry, and Western blotting were used to determine the expression of claudin 1, claudin 2, zonula occludens-1 protein (ZO-1), and F-actin proteins in each rat colon tissue following treatment.
RESULTS
QFLZ significantly alleviated the structural disorganization in the form of epithelial glands in the intestinal mucosa of rats with UC and retarded the progression of the disease. The intestinal mucosal epithelial cells of UC rats showed decreased expression of claudin 1, ZO-1, F-actin ( 0.05), claudin 2 appeared elevated ( 0.05), which resulted in impaired TJ. Treatment with QFLZ resulted in elevated expression of claudin 1 ( 0.05), ZO-1 ( 0.05) and F-actin ( 0.05) and decreased expression of claudin 2 ( 0.05), which allowed for repair of the intestinal mucosal TJ, which in turn served as a treatment for UC.
CONCLUSIONS
The mechanism of repairing TJ function and repairing the intestinal mucosal barrier by QFLZ may be associated with up-regulation of claudin 1, ZO-1, and F-actin levels, and down-regulation of claudin 2 expression level.
目的
探讨芪附理中灌肠方干预脾肾阳虚型溃疡性结肠炎（UC）大鼠模型的疗效及作用机制。
方法
72 只雄性 Sprague-Dawley 大鼠随机分为 6 组：正常模型组、美沙拉嗪组及芪附理中灌肠方高、中、低剂量组，每组 12 只。适应性喂养 3d 后，除正常组外，其余各组均采用大黄煎剂联合三硝基苯磺酸（TNBS）/55%乙醇诱导 UC 大鼠模型。建模成功后，正常组和模型组每日给予生理盐水灌肠，中药组和西药组分别给予芪附理中灌肠方和美沙拉嗪灌肠液治疗 2 周。采用疾病活动指数评分、苏木精-伊红（HE）染色、免疫组化和 Western blot 法检测各组大鼠结肠组织中紧密连接蛋白（Claudin）1、Claudin 2、闭合蛋白-1（ZO-1）和 F-肌动蛋白（F-actin）蛋白的表达。
结果
芪附理中灌肠方能明显改善 UC 大鼠肠黏膜上皮腺体结构紊乱，延缓疾病进展。UC 大鼠肠黏膜上皮细胞 Claudin 1、ZO-1、F-actin 表达降低（ P < 0.05），Claudin 2 表达升高（ P < 0.05），导致 TJ 受损。芪附理中灌肠方治疗后 Claudin 1（ P < 0.05）、ZO-1（ P < 0.05）和 F-actin（ P < 0.05）表达升高，Claudin 2（ P < 0.05）表达降低，促进了肠黏膜 TJ 的修复，从而起到治疗 UC 的作用。
结论
芪附理中灌肠方修复 TJ 功能和修复肠黏膜屏障的作用机制可能与上调 Claudin 1、ZO-1、F-actin 水平和下调 Claudin 2 表达水平有关。
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