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贵州中医药大学药学院,贵阳 550025
Published:30 November 2023,
Received:06 April 2023,
Revised:27 August 2023,
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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 Δ[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 Δ[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.
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。
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 investigation 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 increased 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.
艳山姜总黄酮胃黏膜细胞微RNA-146a-5p肿瘤坏死因子受体关联因子6抗胃溃疡作用
gastric mucosa cellmicroRNA-146a-5pTNF receptor-associated factor 6anti-gastric ulcer effect
魏晴,李玮,柴桂芳. 苗族药艳山姜的研究进展[J]. 中国实验方剂学杂志,2020,26(11):206-216.
WEI Q,LI W,CHAI G F. Research progress on Miao medicine of Alpinia zerumbet[J]. Chin J Exp Tradit Med Formulae,2020,26(11):206-216.
魏晴,梁珊珊,熊瑞,等. 艳山姜提取物对急性胃溃疡模型小鼠的保护作用研究[J]. 中国药房,2020,31(18):2190-2195.
WEI Q,LIANG S S,XIONG R,et al. Study on the protective effect of Alpinia zerumbet extract on acute gastric ulcer model mice[J]. China Pharm,2020,31(18):2190-2195.
HSU S Y. Effects of the constituents of Alpinia speciosa rhizome on experimental ulcers[J]. Taiwan Yi Xue Hui Za Zhi,1987,86(1):58-64.
MPALANTINOS M A,DE MOURA R S,PARENTE J P,et al. Biologically active flavonoids and kava pyrones from the aqueous extract of Alpinia zerumbet[J]. Phytother Res,1998,12(6):442-444.
CHAKRABORTY S,YADAV S K,SAHA B,et al. A bis-resorcinol resveratrol congener prevents indomethacin-induced gastric ulceration by inhibiting TNF-α as well as NF-κB and JNK pathways[J]. Free Radic Res,2019,53(6):596-610.
余永豪. 胃癌中miR-146a和LIN52表达及其与化疗敏感性和预后的关系[J]. 现代肿瘤医学,2020,28(13):2274-2279.
YU Y H. Expressions of miR-146a and LIN52 in gastric cancer and their relationships with chemosensitivity and prognosis[J]. J Mod Oncol,2020,28(13):2274-2279.
尹斌. miR-146a在应激性溃疡中调控作用的研究[D]. 太原:山西医科大学,2018.
YIN B. Study on the regulatory role of miR-146a in stress ulcer[D]. Taiyuan:Shanxi Medical University,2018.
YU X,LU J F,GAO M Q,et al. MiR-146a-5p promotes dental stem cells osteo/odontogenic differentiation through NF-kappa B signaling pathway by targeting TRAF6[J]. Chin J Dent Res,2022,25(4):269-275.
LIN K W,WANG Y,GONG J W,et al. Protective effects of total flavonoids from Alpinia officinarum rhizoma against ethanol-induced gastric ulcer in vivo and in vitro[J]. Pharm Biol,2020,58(1):854-862.
ZHOU D,YANG Q,TIAN T,et al. Gastroprotective effect of gallic acid against ethanol-induced gastric ulcer in rats:involvement of the Nrf2/HO-1 signaling and anti-apoptosis role[J]. Biomedecine Pharmacother,2020,126:110075.
HUA T,YANG M,SONG H H,et al. Huc-MSCs-derived exosomes attenuate inflammatory pain by regulating microglia pyroptosis and autophagy via the miR-146a-5p/TRAF6 axis[J]. J Nanobiotechnology,2022,20(1):324.
CHU T S,XU X,RUAN Z M,et al. MiR-146a contributes to atherosclerotic plaque stability by regulating the expression of TRAF6 and IRAK-1[J]. Mol Biol Rep,2022,49(6):4205-4216.
LI Y L,TAN S L,SHEN Y Y,et al. MiR-146a-5p negatively regulates the IL-1β-stimulated inflammatory response via downregulation of the IRAK1/TRAF6 signaling pathway in human intestinal epithelial cells[J]. Exp Ther Med,2022,24(4):615.
ASLANI M R,SHARGHI A,BOSKABADY M H,et al. Altered gene expression levels of IL-17/TRAF6/MAPK/USP25 axis and pro-inflammatory cytokine levels in lung tissue of obese ovalbumin-sensitized rats[J]. Life Sci,2022,296:120425.
WEN L B,SUN W,XIA D Y,et al. The m6A methyltransferase METTL3 promotes LPS-induced microglia inflammation through TRAF6/NF-κB pathway[J]. Neuroreport,2022,33(6):243-251.
AZIZ R S,SIDDIQUA A,SHAHZAD M,et al. Oxyresveratrol ameliorates ethanol-induced gastric ulcer via downregulation of IL-6,TNF-α,NF-ĸB,and COX-2 levels,and upregulation of TFF-2 levels[J]. Biomedecine Pharmacother,2019,110:554-560.
BAE J Y,PARK W S,KIM H J,et al. Protective effect of carotenoid extract from orange-fleshed sweet potato on gastric ulcer in mice by inhibition of NO,IL-6 and PGE2 production[J]. Pharmaceuticals,2021,14(12):1320.
FU S,CHEN J M,ZHANG C,et al. Gastroprotective effects of Periplaneta americana L. extract against ethanol-induced gastric ulcer in mice by suppressing apoptosis-related pathways[J]. Front Pharmacol,2021,12:798421.
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