|
|
|
| Exploration of the Effect of Weiling Decoction on Intestinal Barrier Function in Rats with Diarrhea-Type Irritable Bowel Syndrome Based on MLCK/MLC2 Signaling Pathway |
| ZHANG Yanyan, YAN Bo, GUO Husheng, et al |
| The Second People's Hospital of Hefei, Anhui Hefei 230011, China |
|
|
|
|
Abstract Objective: To observe the effect of Weiling Decoction (WLD) on intestinal barrier function in rats with diarrhea-type irritable bowel syndrome (IBS-D) and to explore its possible mechanism based on the MLCK/MLC2 signaling pathway. Methods: Fifty SD rats were randomly divided into a control group (CON group), a model group (IBS-D group), a pinaverium bromide group (PB group, 0.13mg/kg), a low-dose Weiling Decoction group (WLD-L group, 5.31g/kg), and a high-dose Weiling Decoction group (WLD-H group, 10.62g/kg), with 10 rats in each group. The IBS-D rat model was established using acetic acid enema combined with chronic restraint stress. After successful modeling, the rats in each drug group were administered the corresponding drug by gavage once daily for 14 consecutive days. After the drug administration, the diarrhea index and abdominal wall withdrawal reflex score of rats in each group were detected. Intestinal permeability was assessed using fluorescein isothiocyanate-labeled dextran (FITC-dextran). Histopathological changes in colonic tissue were observed by hematoxylin-eosin (HE) staining. Inflammatory factors (TNF-α, IL-6, IL-1β) in colonic tissue were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the expression levels of tight junction proteins (ZO-1, occludin, claudin-1) and MLCK/MLC2 signaling pathway-related proteins (MLCK, MLC2, p-MLC2) in colonic tissue. Results: Compared with the IBS-D group, the diarrhea index, abdominal wall withdrawal reflex score, intestinal permeability, and levels of inflammatory factors TNF-α, IL-6, and IL-1β were significantly reduced in the PB, WLD-L, and WLD-H groups (P<0.05). The degree of intestinal villus damage in colonic tissue was significantly alleviated, and the expression levels of tight junction proteins ZO-1, occludin, and claudin-1 were significantly increased (P<0.05). Additionally, the expression levels of MLCK/MLC2 signaling pathway-related proteins MLCK and p-MLC2/MLC2 were significantly decreased (P<0.05). The results of the above indicators in the PB and WLD-H groups were superior to those in the WLD-L group (P<0.05). Conclusion: WLD can improve intestinal barrier function in IBS-D rats by inhibiting the MLCK/MLC2 signaling pathway, downregulating the expression of inflammatory factors, and upregulating the expression of tight junction proteins in the intestine.
|
|
|
|
|
|
[1] 卞立群,黄绍刚,魏玮,等.肠易激综合征中医诊疗专家共识(2024)[J].中医杂志,2024,65(18):1948-1956.
[2] 曾旺晴,刘新文.胃苓汤联合美沙拉嗪肠溶片治疗溃疡性结肠炎脾虚湿蕴证临床观察[J].光明中医,2024,39(9):1840-1843.
[3] 耿永亮.黄芪建中汤合胃苓汤治疗脾胃虚寒型胃脘痛的治疗效果[J].内蒙古中医药,2024,43(6):3-4.
[4] Xie Y,Zhan X,Tu J,et al.Atractylodes oil alleviates diarrhea-predominant irritable bowel syndrome by regulating intestinal inflammation and intestinal barrier via SCF/c-kitand MLCK/MLC2 pathways[J].Ethnopharmacol,2021,272(2):113925-113933.
[5] 赖碧玉,洪梦颖,李兴,等.乙酸灌肠联合束缚夹尾应激诱导肝郁脾虚型腹泻型肠易激综合征大鼠模型的制备[J].中国实验动物学报,2024,32(3):317-328.
[6] Zhang SH,Tian DM,Xia ZX,et al.Chang-Kang-Fang alleviates diarrhea predominant irritable bowel syndrome (IBS-D) through inhibiting TLR4/NF-κB/NLRP3 pathway[J].Ethnopharmacol,2024,330(10):118236.
[7] Ji SY,Zhang Q.Momordica charantia polysaccharides alleviate diarrhea-predominant irritable bowel syndrome by regulating intestinal inflammation and barrier via NF-κB pathway[J].Allergol Immunopathol,2022,50(3):62-70.
[8] 李孟,郭艳辉,刘珂宏,等.黄芩汤治疗小儿湿热型腹泻的疗效及对血清IL-6、IL-10、TNF-α水平的影响[J].时珍国医国药,2022,33(5):1161-1163.
[9] Chu Y,Zhu Y,Zhang Y,et al.Tetrandrine attenuates intestinal epithelial barrier defects caused by colitis through promoting the expression of Occludin via the AhR-miR-429 pathway[J].Faseb,2021,35(5):21502.
[10] Huang S,Fu Y,Xu B,et al.Wogonoside alleviates colitis by improving intestinal epithelial barrier function via the MLCK/pMLC2 pathway[J].Phytomedicine,2020,68(1):153179-153189. |
|
|
|
2025, Vol. 31 
