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Panax Notoginseng Saponin Attenuates Gastric Mucosal Epithelial Cell Injury Induced by Dual Antiplatelet Drugs through COX and PI3K/Akt/ VEGF-GSK-3β-RhoA Network Pathway*- Chinese Journal of Integrative Medicine Vol. 27, Issue 11, Pages: 819-824(2021)
- Affiliations：
1.Beijing First Hospital of Integrated Chinese and Western Medicine, Beijing (100039), China
2.Center for Cardiovascular Disease, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing (100091), China
3.Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing (100102), China
- Author bio：
Dr. JIANG Hong-yan, E-mail: billhappy@yeah.net.
- Funds：
DOI：10.1007/s11655-021-2854-3
CLC：Published：01 November 2021，
Published Online：15 January 2021，
Accepted：18 December 2019
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Ming-ming WANG, Mei XUE, Zhong-hai XIN, et al.
Panax Notoginseng Saponin Attenuates Gastric Mucosal Epithelial Cell Injury Induced by Dual Antiplatelet Drugs through COX and PI3K/Akt/ VEGF-GSK-3β-RhoA Network Pathway*. [J]. Chinese Journal of Integrative Medicine 27(11):819-824(2021)Ming-ming WANG, Mei XUE, Zhong-hai XIN, et al.
Panax Notoginseng Saponin Attenuates Gastric Mucosal Epithelial Cell Injury Induced by Dual Antiplatelet Drugs through COX and PI3K/Akt/ VEGF-GSK-3β-RhoA Network Pathway*. [J]. Chinese Journal of Integrative Medicine 27(11):819-824(2021) DOI： 10.1007/s11655-021-2854-3.
摘要
目的:
2
观察PNS对双抗诱导的胃粘膜上皮细胞凋亡和通透性升高的影响
并从COX通路和PI3K/Akt通路探讨其作用机制.
方法:
2
体外培养人胃粘膜上皮细胞 (GES-1)
随机分为空白组、双抗组、PNS+双抗组、LY294002+PNS+双抗组. 流式细胞术检测GES-1凋亡率
酶标仪测定GES-1细胞通透性
放免法检测GES-1细胞培养上清液PGE2、6-keto-PGF1α浓度
ELISA法检测GES-1细胞培养上清液血管内皮细胞生长因子 (Vascular endothelial growth factor
VEGF) 浓度. Western-blot检测GES-1中COX-1、COX-2、PI3K、p-PI3K、Akt、p-Akt、GSK-3β、RhoA、GTP-RhoA蛋白表达.
结果:
2
与空白组比较
双抗组GES-1凋亡率、通透性均显著升高 (
P
<
0.05)
PGE2、6-keto-PGF1α和VEGF浓度均降低 (
P
<
0.05)
COX-1、p-PI3K、p-Akt蛋白表达均降低 (
P
<
0.05)
COX-2、GTP-RhoA、GSK-3β蛋白表达均升高 (
P
<
0.05) . 与双抗组比较
PNS+双抗组GES-1凋亡率与通透性均降低 (
P
<
0.05)
PGE2、6-keto-PGF1α和VEGF浓度均升高 (
P
<
0.05)
COX-1、p-PI3K、p-Akt蛋白表达均升高 (
P
<
0.05)
COX-2、GTP-RhoA、GSK-3β蛋白表达均降低 (
P
<
0.05) ; 加入LY294002后
COX-1和COX-2蛋白表达无影响 (
P
>
0.05)
GES-1凋亡率和通透性均显著升高 (
P
<
0.05)
GTP-RhoA及GSK-3β蛋白表达均升高 (
P
<
0.05) .
结论:
2
PNS可以减轻双抗对胃粘膜上皮细胞中COX/PG通路的抑制
减轻双抗诱导的胃粘膜上皮细胞凋亡和通透性升高
机制涉及对胃粘膜上皮细胞PI3K/Akt/GSK-3β-VEGF-RhoA通路的调节.
Abstract
Objective:
2
To elucidate the underlying mechanism of
Panax notoginseng
saponin (PNS) on gastric epithelial cell injury and barrier dysfunction induced by dual antiplatelet (DA).
Methods:
2
Human gastric mucosal epithelial cell (GES-1) was cultured and divided into 4 groups: a control
a DA
a PNS+DA and a LY294002+PNS+DA group. GES-1 apoptosis was detected by flow cytometry
cell permeability were detected using Transwell
level of prostaglandins E2 (PGE2)
6-keto-prostaglandin F1α (6-keto-PGF1α) and vascular endothelial growth factor (VEGF) in supernatant were measured by enzyme linked immunosorbent assay (ELISA)
expression of phosphatidylinositide 3-kinase (PI3K)
phosphorylated-PI3K (p-PI3K)
Akt
phosphorylated-Akt (p-Akt)
cyclooxygenase-1 (COX-1)
cyclooxygenase-2 (COX-2)
glycogen synthase kinase-3β (GSK-3β) and Ras homolog gene family member A (RhoA) were measured by Western-blot.
Results:
2
DA induced apoptosis and hyper-permeability in GES-1
reduced supernatant level of PGE2
6-keto-PGF1α and VEGF (
P
<
0.05). Addition of PNS reduced the apoptosis of GES-1 caused by DA
restored the concentration of PGE2
6-keto-PGF1α and VEGF (
P
<
0.05). In addition
PNS attenuated the alteration of COX-1 and COX-2 expression induced by DA
up-regulated p-PI3K/p-Akt
down-regulated RhoA and GSK-3β. LY294002 mitigated the effects of PNS on cell apoptosis
cell permeability
VEGF concentration
and expression of RhoA and GSK-3β significantly.
Conclusions:
2
PNS attenuates the suppression on COX/PG pathway from DA
alleviates DA-induced GES-1 apoptosis and barrier dysfunction through PI3K/Akt/ VEGF-GSK-3β-RhoA network pathway.
关键词
Keywords
Panax notoginseng saponinsdual antiplateletpermeabilitycyclooxygenasePI3K
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