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[黄精水提取物通过TRAF1/ASK1/JNK途径对过量食用辛辣物质和酒精诱导的小鼠胃黏膜损伤的保护作用]

[Protective effect of Polygonati Rhizoma aqueous extract on gastric mucosal injury in mice induced by overtaking pungent substances and alcohol via TRAF1/ASK1/JNK pathway].

作者信息

Dong Zi-Mo, Wei Ke-Jian, Zhang Wen-Long, Zhang Hui-Wen, Zhou Heng-Pu, Chen Yu-Lan, Lyu Gui-Yuan, Su Jie

机构信息

School of Pharmaceutical Sciences, Zhejiang Chinese Medical University Hangzhou 310053, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2024 Oct;49(20):5505-5515. doi: 10.19540/j.cnki.cjcmm.20240701.401.

DOI:10.19540/j.cnki.cjcmm.20240701.401
PMID:39701734
Abstract

This study aims to investigate the effect and potential mechanism of Polygonati Rhizoma aqueous extract in protecting mice from gastric mucosal injury(stomach Yin deficiency). ICR mice were administrated with the mixture of pungent substance extract and alcohol by gavage once a day for 6 weeks to establish the mouse model of gastric mucosal injury with gastric Yin deficiency. The modeled mice were randomized into three groups of model and Polygonati Rhizoma aqueous extract administrated at 0.5 g·kg(-1) and 1.0 g·kg(-1) according to the body weight. The mice were then continuously administrated with the molding agent once a day, and those in the Polygonati Rhizoma aqueous extract groups were additionally administrated the extract for 7 weeks. During this period, traditional Chinese medicine syndrome indicators related to gastric Yin deficiency were tested. After the last administration, the gastric tissue was collected to observe the histomorphological changes. The activities of antioxidant enzymes in the gastric homogenate were measured, and the levels and expression of proinflammatory cytokines in the gastric tissue were measured by enzyme-linked immunosorbent assay and immunohistochemistry, respectively. The expression levels of proteins in the tumor necrosis factor receptor(TNFR)-associated factor 1(TRAF1)/apoptosis signal regulating kinase 1(ASK1)/c-Jun N-terminal kinase(JNK) pathway were determined by Western blot, and those of apoptosis factors were determined by immunofluorescence. The results showed that the Polygonati Rhizoma aqueous extract alleviated the stomach Yin deficiency in mice, ameliorated gastric mucosal lesions, increased the activities of antioxidant enzymes in the gastric tissue(P<0.05, P<0.01), lowered the levels of pro-inflammatory cytokines in the gastric tissue(P<0.05, P<0.01), down-regulated the expression levels of proteins in the TRAF1/ASK1/JNK pathway(P<0.01) and pro-apoptotic factors in the gastric tissue, and up-regulated the expression of B-cell lymphoma-2(Bcl-2). The results suggested that the Polygonati Rhizoma aqueous extract could alleviate the symptoms of stomach Yin deficiency, such as hunger without desire to eat, thirst, and dry stool, and mitigate the gastric mucosal injury caused by overtaking pungent substances and alcohol by inhibiting the TRAF1/ASK1/JNK pathway to reduce apoptosis and inflammation in the gastric tissue.

摘要

本研究旨在探讨黄精水提取物对胃阴虚型小鼠胃黏膜损伤的保护作用及潜在机制。将ICR小鼠每天灌胃给予辛辣物质提取物和乙醇的混合物,持续6周,以建立胃阴虚型胃黏膜损伤小鼠模型。将造模成功的小鼠按体重随机分为模型组、0.5 g·kg⁻¹黄精水提取物组和1.0 g·kg⁻¹黄精水提取物组。然后小鼠每天继续给予造模剂,黄精水提取物组小鼠额外给予提取物7周。在此期间,检测与胃阴虚相关的中医证候指标。末次给药后,采集胃组织观察组织形态学变化。检测胃匀浆中抗氧化酶的活性,分别采用酶联免疫吸附测定法和免疫组织化学法检测胃组织中促炎细胞因子的水平和表达。通过蛋白质免疫印迹法测定肿瘤坏死因子受体(TNFR)相关因子1(TRAF1)/凋亡信号调节激酶1(ASK1)/c-Jun氨基末端激酶(JNK)通路中蛋白的表达水平,通过免疫荧光法测定凋亡因子的表达水平。结果显示,黄精水提取物可改善小鼠胃阴虚症状,减轻胃黏膜损伤,提高胃组织中抗氧化酶的活性(P<0.05,P<0.01),降低胃组织中促炎细胞因子的水平(P<0.05,P<0.01),下调胃组织中TRAF1/ASK1/JNK通路蛋白的表达水平(P<0.01)以及促凋亡因子的表达,上调B细胞淋巴瘤-2(Bcl-2)的表达。结果提示,黄精水提取物可缓解胃阴虚症状,如饥不欲食、口渴、大便干结等,通过抑制TRAF1/ASK1/JNK通路减轻过食辛辣物质和乙醇所致的胃黏膜损伤,减少胃组织细胞凋亡和炎症反应。

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