Preventive and inhibitive effects of Yiwei Xiaoyu granules on the development and progression of spasmolytic polypeptide-expressing metaplasia lesions.
Preventive and inhibitive effects of Yiwei Xiaoyu granules on the development and progression of spasmolytic polypeptide-expressing metaplasia lesions.
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益胃消瘀颗粒对解痉多肽化生病变发生发展的预防和抑制作用
DOI：
10.4251/wjgo.v13.i11.1741
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发表时间：
2021-11-15
影响因子：
3
通讯作者：
Li YP
中科院分区：
文献类型：
--
作者：
Chen WQ;Tian FL;Zhang JW;Yang XJ;Li YP
背景痉挛性多肽表达化生（SPEM）是一种潜在的癌前病变。目的探讨益胃消瘀颗粒（YWXY）对微小RNA（miR）-7介导的SPEM病变的预防和抑制作用。方法收集慢性萎缩性胃炎患者和健康体检者的胃粘膜活检标本，并签署知情同意书。给三苯氧胺诱发的SPEM小鼠灌胃YWXY，于实验第10天取胃粘膜。通过免疫组化和免疫荧光法对SPEM、病变进行验证，并探讨其可能的机制。逆转录-定量聚合酶链反应检测RNA转录本。结果miR-7在SPEM病变中表达下调，三叶因子2（TFF 2）和丛生蛋白在人胃黏膜中表达上调。体内实验表明，愈胃消瘀汤可通过调节Ki 67抑制三苯氧胺诱导的SPEM损伤中的细胞增殖。同时，免疫荧光法检测到YWXY可通过调节TFF 2恢复miR-7的表达，而逆转录-定量聚合酶链反应检测不到，提示YWXY可能通过介导TFF 2靶向miR-7。结果提示，益胃消瘀汤治疗后3 d内，血管内皮生长因子-β和胃内因子的表达均恢复正常，提示益胃消瘀汤可能通过调节血管内皮生长因子-β和胃内因子的表达来抑制SPEM的发生、发展。结论miR-7表达下调是SPEM的早期事件，可能通过调节胃黏膜中TFF 2的表达而实现。在SPEM小鼠模型中，YWXY能够通过介导TFF 2抑制细胞增殖并恢复miR-7的表达。
BACKGROUND Spasmolytic polypeptide-expressing metaplasia (SPEM) is a potential preneoplastic lesion. AIM To elucidate the microRNA (miR)-7-mediated preventive and inhibitive effects of Yiwei Xiaoyu granules (YWXY) in SPEM lesions. METHODS Gastric mucosa biopsies were collected from chronic atrophic gastritis patients and healthy people with signed informed consent. YWXY was administered to the mice with induced SPEM by tamoxifen, and the gastric mucosa was harvested on the tenth day of the experiment. Then immunohistochemistry and immunofluorescence were performed to validate the SPEM, lesions and the potential mechanism was investigated. RNA transcripts were detected with reverse transcription-quantitative polymerase chain reaction. RESULTS The expression of miR-7 was downregulated in the SPEM lesions, and expression of trefoil factor 2 (TFF2) and clusterin was high in the human gastric mucosa. In vivo experiments showed that YWXY could inhibit the cell proliferation in the tamoxifen-induced SPEM lesions by regulating Ki67. Simultaneously, YWXY could restore the expression of miR-7 by regulating TFF2 by detection with immunofluorescence but not with reverse transcription-quantitative polymerase chain reaction, indicating its potential mechanism of targeting miR-7 by mediating TFF2. The expression of vascular endothelial growth factor-β and gastric intrinsic factor was restored within 3 d of YWXY administration for the SPEM lesions, speculating that the possible mechanism of YWXY is to inhibit the development and progression of SPEM by regulating vascular endothelial growth factor-β and gastric intrinsic factor. CONCLUSION miR-7 downregulation is an early event in SPEM through regulation of TFF2 in human gastric mucosa. YWXY is able to inhibit the cell proliferation and restore the expression of miR-7 by mediating TFF2 in the SPEM mouse model.
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