薇转安对胃癌前病变大鼠的影响：调节胃黏膜微生物群与炎症因子机制研究

Effects of Weizhuan'an on rats with precancerous lesions of gastric cancer based on regulating gastric mucosal microflora and inflammatory factors

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Frontiers in Pharmacology

影响因子:4.8

分区:医学3区 / 药学3区

发表日期:2024

作者: Yuting Lu, Huayi Liu, Jiaju Shang, Yijia Mao, Lingkai Meng, Changbai Gao

DOI: 10.3389/fphar.2024.1446244

摘要

本研究旨在观察薇转安方对胃癌前病变（PLGC）大鼠的干预作用及其对胃黏膜微生物群和炎症因子的调节作用，并探讨其药效机制。将大鼠随机分为空白对照组（BCG）、不同剂量的薇转安方低、中、高剂量组（LDG、MDG、HDG）以及自然恢复组（NRG）。给予药物的剂量对应的薇转安方制剂，NRG和BCG组则给予等体积蒸馏水，持续12周。取出大鼠胃黏膜样本，观察其整体和病理变化；采用16S rDNA扩增子测序检测胃黏膜微生物群变化，利用细胞因子抗体微阵列和Western印迹分析炎症因子。结果显示，与BCG组相比，PLGC大鼠的胃黏膜病理、微生物群和炎症因子均显著变化，尤其在MDG和HDG组得到明显改善（p < 0.05）。与NRG组相比，益生菌如乳酸杆菌和Veillonella的丰度增加，病原菌如变形菌门和假单胞菌的丰度降低（p < 0.05，p < 0.01），胃黏膜中IL-2、IL-4、IL-13和MCP-1的相对含量降低（p < 0.05）。同时，上调DNA结合转录调节因子、ABC型多药运输系统及相关酶的表达，显著影响病毒蛋白与细胞因子及受体、T细胞受体等信号通路（p < 0.05，p < 0.01），促进药物吸收利用和修复受损的胃黏膜。本研究证实，薇转安方通过调节胃黏膜微生物群和炎症因子，可有效治疗大鼠PLGC。

Abstract

This study aimed to observe the intervention of Weizhuan'an prescription on rats with precancerous lesions of gastric cancer (PLGC) as well as its regulation on gastric mucosal microflora and inflammatory factors and explore the pharmacodynamic mechanisms of Weizhuan'an Formula.The rats were classified into the blank control group (BCG); low-, medium-, and high-dose groups of Weizhuan'an prescription (LDG, MDG, and HDG, respectively); and natural recovery group (NRG) at random. The rats in the traditional Chinese medicine (TCM) group were given corresponding doses of Weizhuan'an formula, while the rats in the NRG and BCG were given an equivalent volume of distilled water for 12 weeks. After that, gastric mucosa samples of rats were collected to observe the general and pathological changes in the gastric mucosa; the changes in gastric mucosal microflora were detected by 16S rDNA amplicon sequencing, and the inflammatory factors were analyzed by cytokine antibody microarray and Western blotting.The results suggest that compared with the BCG, the pathology of gastric mucosa and gastric mucosal microflora and inflammatory factors in rats with PLGC have changed significantly, while Weizhuan'an formula effectively improved them, especially in the MDG and HDG (p < 0.05). Compared with the NRG, the abundance of probiotics such as Lactobacillus and Veillonella were increased, while the abundance of pathogens such as Proteobacteria and Pseudomonas was decreased (p < 0.05, p < 0.01), and the relative contents of IL-2, IL-4, IL-13, and MCP-1 in gastric mucosa were decreased (p < 0.05). Moreover, it can upregulate the DNA-binding transcriptional regulator, ABC type multidrug transport system, and related enzymes and affect the signaling pathways such as viral protein interaction with cytokine and cytokine receptor and T cell receptor signaling pathway significantly (p < 0.05, p < 0.01), which can promote drug absorption and utilization and repair damaged gastric mucosa.The study confirmed that Weizhuan'an prescription can treat rats with PLGC by regulating gastric mucosal microflora and inflammatory factors.