Beijing First Hospital of Integrated Chinese and Western Medicine, Beijing, 100039, China.
Center for Cardiovascular Disease, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
Chin J Integr Med. 2021 Nov;27(11):819-824. doi: 10.1007/s11655-021-2854-3. Epub 2021 Jan 15.
To elucidate the underlying mechanism of Panax notoginseng saponin (PNS) on gastric epithelial cell injury and barrier dysfunction induced by dual antiplatelet (DA).
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.
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.
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.
阐明三七总皂苷（PNS）对双联抗血小板（DA）诱导的胃上皮细胞损伤和屏障功能障碍的作用机制。
培养人胃黏膜上皮细胞（GES-1），并分为 4 组：对照组、DA 组、PNS+DA 组和 LY294002+PNS+DA 组。流式细胞术检测 GES-1 细胞凋亡，Transwell 检测细胞通透性，酶联免疫吸附试验（ELISA）检测上清液中前列腺素 E2（PGE2）、6-酮-前列腺素 F1α（6-keto-PGF1α）和血管内皮生长因子（VEGF）的水平，Western blot 检测磷脂酰肌醇 3-激酶（PI3K）、磷酸化-PI3K（p-PI3K）、Akt、磷酸化-Akt（p-Akt）、环氧化酶-1（COX-1）、环氧化酶-2（COX-2）、糖原合成酶激酶-3β（GSK-3β）和 Ras 同源基因家族成员 A（RhoA）的表达。
DA 诱导 GES-1 细胞凋亡和高通透性，降低上清液中 PGE2、6-keto-PGF1α 和 VEGF 的水平（P<0.05）。PNS 可减少 DA 诱导的 GES-1 细胞凋亡，恢复 PGE2、6-keto-PGF1α 和 VEGF 的浓度（P<0.05）。此外，PNS 可减轻 DA 诱导的 COX-1 和 COX-2 表达改变，上调 p-PI3K/p-Akt，下调 RhoA 和 GSK-3β。LY294002 显著减轻 PNS 对细胞凋亡、细胞通透性、VEGF 浓度以及 RhoA 和 GSK-3β 表达的影响。
PNS 通过 PI3K/Akt/VEGF-GSK-3β-RhoA 通路减轻 DA 对 COX/PG 通路的抑制，减轻 DA 诱导的 GES-1 细胞凋亡和屏障功能障碍。
