<italic style="font-style: italic">Panax Notoginseng</italic> Saponin Attenuates Gastric Mucosal Epithelial Cell Injury Induced by Dual Antiplatelet Drugs through COX and PI3K/Akt/ VEGF-GSK-3β-RhoA Network Pathway<sup>*</sup>

Ming-ming WANG; Mei XUE; Zhong-hai XIN; Yan-hui WANG; Rui-jie LI; Hong-yan JIANG; Da-zhuo SHI

doi:10.1007/s11655-021-2854-3

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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^*

Original Article | Updated：2021-11-05

- 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^*
- 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 2021年27卷第11期页码：819-824
- 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：
  
  the National Natural Science Foundation of China(81273933;81102722);the Eleven Five-Year Plan of National Science and Technology Support Project(2006BAI04A01-2);the Jilin Province Major Science and Technology Achievement Transforming Project(11ZDZH005)
- DOI：10.1007/s11655-021-2854-3
  中图分类号：
- 纸质出版日期：2021-11-01，
  
  网络出版日期：2021-01-15，
  
  录用日期：2019-12-18
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Ming-ming WANG, Mei XUE, Zhong-hai XIN, 等. 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, 2021,27(11):819-824.

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, 2021,27(11):819-824.
Ming-ming WANG, Mei XUE, Zhong-hai XIN, 等. 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, 2021,27(11):819-824. DOI： 10.1007/s11655-021-2854-3.

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, 2021,27(11):819-824. DOI： 10.1007/s11655-021-2854-3.

摘要

目的:

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:

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:

与空白组比较

双抗组GES-1凋亡率、通透性均显著升高 (

0.05)

PGE2、6-keto-PGF1α和VEGF浓度均降低 (

0.05)

COX-1、p-PI3K、p-Akt蛋白表达均降低 (

0.05)

COX-2、GTP-RhoA、GSK-3β蛋白表达均升高 (

0.05) . 与双抗组比较

PNS+双抗组GES-1凋亡率与通透性均降低 (

0.05)

PGE2、6-keto-PGF1α和VEGF浓度均升高 (

0.05)

COX-1、p-PI3K、p-Akt蛋白表达均升高 (

0.05)

COX-2、GTP-RhoA、GSK-3β蛋白表达均降低 (

0.05) ; 加入LY294002后

COX-1和COX-2蛋白表达无影响 (

0.05)

GES-1凋亡率和通透性均显著升高 (

0.05)

GTP-RhoA及GSK-3β蛋白表达均升高 (

0.05) .

结论:

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:

To elucidate the underlying mechanism of

Panax notoginseng

saponin (PNS) on gastric epithelial cell injury and barrier dysfunction induced by dual antiplatelet (DA).

Methods:

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:

DA induced apoptosis and hyper-permeability in GES-1

reduced supernatant level of PGE2

6-keto-PGF1α and VEGF (

0.05). Addition of PNS reduced the apoptosis of GES-1 caused by DA

restored the concentration of PGE2

6-keto-PGF1α and VEGF (

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:

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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Panax Notoginseng Saponins Inhibits Ventricular Remodeling after Myocardial Infarction in Rats Through Regulating ATF3/MAP2K3/p38 MAPK and NFκB Pathway

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*

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*

DOI：10.1007/s11655-021-2854-3

摘要

Abstract

关键词

Keywords

references

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^*

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^*