Improvement effect and mechanism of total flavonoids from
Alpinia zerumbet on gastric mucosa injury induced by absolute ethanol- ZHONGGUO YAOFANG Vol. 34, Issue 22, Pages: 2701-2707(2023)
- 作者机构：
贵州中医药大学药学院，贵阳 550025
- 作者简介：
- 基金信息：
DOI：10.6039/j.issn.1001-0408.2023.22.03
CLC： R965Received：06 April 2023，
Revised：2023-08-27，
Accepted：26 September 2023，
Published：30 November 2023
- 稿件说明：
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魏晴,薛娟,梁珊珊.艳山姜总黄酮改善无水乙醇致胃黏膜细胞损伤的作用及机制 [J].中国药房,2023,34(22):2701-2707.
WEI Qing,XUE Juan,LIANG Shanshan.Improvement effect and mechanism of total flavonoids from Alpinia zerumbet on gastric mucosa injury induced by absolute ethanol[J].ZHONGGUO YAOFANG,2023,34(22):2701-2707.
魏晴,薛娟,梁珊珊.艳山姜总黄酮改善无水乙醇致胃黏膜细胞损伤的作用及机制 [J].中国药房,2023,34(22):2701-2707. DOI： 10.6039/j.issn.1001-0408.2023.22.03.
WEI Qing,XUE Juan,LIANG Shanshan.Improvement effect and mechanism of total flavonoids from Alpinia zerumbet on gastric mucosa injury induced by absolute ethanol[J].ZHONGGUO YAOFANG,2023,34(22):2701-2707. DOI： 10.6039/j.issn.1001-0408.2023.22.03.
摘要
目的
2
探讨艳山姜总黄酮通过微RNA-146a-5p（miR-146a-5p）对无水乙醇诱导的胃黏膜细胞损伤的改善作用及潜在机制。
方法
2
以人胃黏膜细胞GES-1为对象，以无水乙醇诱导建立急性胃溃疡细胞模型，在考察不同质量浓度艳山姜总黄酮对细胞活力影响及筛选作用浓度的基础上，检测细胞中miR-146a-5p的相对表达量，细胞中肿瘤坏死因子受体关联因子6（TRAF6）、核因子κB p65（NF-κB p65）、肿瘤坏死因子α（TNF-α）蛋白的表达水平，以及细胞上清液中白细胞介素1β（IL-1β）、IL-6、前列腺素E
2
（PEG
2
）水平；验证miR-146a-5p与TRAF6的靶向关系，并观察过表达miR-146a-5p、敲减TRAF6对模型细胞上清液中IL-1β、IL-6、PEG
2
水平的影响，以及敲减miR-146a-5p对艳山姜总黄酮抗胃溃疡作用的影响。
结果
2
与空白组比较，模型组细胞中miR-146a-5p的相对表达量和上清液中PGE
2
水平均显著降低（
P
＜0.01），细胞中TRAF6、NF-κB p65、TNF-α蛋白的表达水平和上清液中IL-1β、IL-6水平均显著升高（
P
＜0.01）。与模型组比较，模型+艳山姜总黄酮（60 mg/L）组细胞中miR-146a-5p的相对表达量和上清液中PGE
2
水平均显著升高（
P
＜0.01），细胞中TRAF6、NF-κB p65、TNF-α蛋白的表达水平和上清液中IL-1β、IL-6水平均显著降低（
P
＜0.05或
P
＜0.01）。miR-146a-5p与TRAF6存在靶向关系且呈负相关；过表达miR-146a-5p或敲减TRAF6后，细胞上清液中IL-1β、IL-6水平均显著降低，PGE
2
水平显著升高（
P
＜0.05）。敲减miR-146a-5p后，艳山姜总黄酮作用下的细胞上清液中IL-1β、IL-6水平和细胞中TRAF6蛋白的表达水平均显著升高，PGE
2
水平显著降低（
P
＜0.05）。
结论
2
艳山姜总黄酮对无水乙醇致胃黏膜细胞损伤有一定的改善作用，其机制可能与上调miR-146a-5p的表达、抑制TRAF6的表达，进而抑制相关炎症因子的分泌有关。
Abstract
OBJECTIVE
2
To explore the improvement effect and potential mechanism of total flavonoids from
Alpinia zerumbet
on gastric mucosa injury induced by absolute ethanol through microRNA-146a-5p （miR-146a-5p）.
METHODS
2
Using human gastric mucosa GES-1 cells as objects， the acute gastric ulcer model was established by absolute ethanol； based on the i
nvestigation of the effects of different concentrations of total flavonoids from
A. zerumbet
on cell activity and the selection of action concentration， the relative expression level of miR-146a-5p in GES-1 cells was detected， the protein expressions of tumor necrosis factor （TNF） receptor-associated factor 6（TRAF6）， nuclear factor-κB p65 （NF-κB p65） and TNF-α were detected， and the levels of interleukin-1β （IL-1β）， IL-6 and prostaglandin E
2
（PGE
2
） in cell supernatant were determined. The targeting relationship between miR-146a-5p and TRAF6 was verified； the effects of overexpressed miR-146a-5p and TRAF6 knockdown on the levels of IL-1β， IL-6 and PEG
2
in supernatant of model cells as well as the effects of miR-146a-5p knockdown on anti-gastric ulcer effect of total flavonoids from
A. zerumbet
were observed.
RESULTS
2
Compared with the blank group， the relative expression of miR-146a-5p in cells and the level of PGE
2
in cell supernatant were decreased significantly in the model group （
P
＜0.01）， while the protein expressions of TRAF6， NF-κB p65 and TNF-α in cells and the levels of IL-1β and IL-6 in cell supernatant were increased significantly （
P
＜0.01）. Compared with the model group， the relative expression of miR-146a-5p in cells and the level of PGE
2
in cell supernatant were increased significantly in model+
A. zerumbet
total flavonoids （60 mg/L） group （
P
＜0.01）， while the protein expressions of TRAF6， NF-κB p65 and TNF-α in cells and the levels of IL-1β and IL-6 in cell supernatant were decreased significantly （
P
＜0.05 or
P
＜0.01）. There was a targeted relationship and a negative correlation between miR-146a-5p and TRAF6. After overexpression of miR-146a-5p or TRAF6 knockdown， the levels of IL-1β and IL-6 were decreased significantly in cell supernatant， while the level of PGE
2
was increase
d significantly （
P
＜0.05）. After miR-146a-5p knockdown， the levels of IL-1β and IL-6 in cell supernatant and the protein expression of TRAF6 in cells administered with total flavonoids of
A. zerumbet
were increased significantly， while the level of PGE
2
was decreased significantly （
P
＜0.05）.
CONCLUSIONS
2
Total flavonoids of
A. zerumbet
can improve the gastric mucosa injury induced by absolute ethanol. The mechanism may be related to up-regulating the expression of miR-146a-5p， inhibiting the expression of TRAF6， and further inhibiting the secretion of related inflammatory factors.
关键词
Keywords
references
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