Ginsenoside Rg1 promotes cerebral angiogenesis via the PI3K/Akt/mTOR signaling pathway in ischemic mice
Ginsenoside Rg1 promotes cerebral angiogenesis via the PI3K/Akt/mTOR signaling pathway in ischemic mice
复制标题
人参皂苷 Rg1 通过 PI3K/Akt/mTOR 信号通路促进缺血小鼠脑血管生成
DOI：
10.1016/j.ejphar.2019.172418
复制
发表时间：
2019-08-05
影响因子：
5
通讯作者：
Xu, Renhao
中科院分区：
文献类型：
--
作者：
Chen, Junmin;Zhang, Xiangjian;Xu, Renhao
血管生成在缺血性脑卒中后的脑重构和神经功能恢复过程中起着重要作用。人参皂苷Rg1对中枢神经系统有保护作用。然而，人参皂苷Rg1对脑缺血时脑血管生成的影响尚不清楚。本研究旨在探讨人参皂苷Rg1对脑血管生成的潜在保护作用及其机制。小鼠在远端大脑中动脉闭塞（dMCAO）后24小时开始，每天给药或人参皂苷Rg1，连续14 d。与dMCAO组相比，人参皂苷Rgl改善了神经行为结果，减少了脑梗死体积。人参皂苷Rg1处理增加了梗死周围皮质区CD31、溴脱氧尿苷(+)/CD31（+）微血管和gfap阳性血管的表达。人参皂苷Rg1组VEGF表达明显增强。体外成功培养人脑微血管内皮细胞（hCMEC/D3），建立氧葡萄糖剥夺（OGD）模型。人参皂苷Rg1显著提高OGD后内皮细胞的增殖、迁移和成管能力，上调VEGF、HIF-1 α、PI3K、p-Akt、p-mTOR的表达。此外，给药PI3K/Akt/mTOR信号通路抑制剂LY294002可消除人参皂苷Rg1的有益作用。综上所述，人参皂苷Rg1通过PI3K/Akt/mTOR信号通路增加VEGF的表达，促进缺血性脑卒中后血管生成。
Angiogenesis plays an important role in the remodeling process of the ischemic brain and the recovery of neurological function after ischemic stroke. Ginsenoside Rg1 has been reported to exert neuroprotective effects on the central nervous system. However, the effects of ginsenoside Rg1 on cerebral angiogenesis in cerebral ischemia remained unclear. The current study aimed to investigate the potential protective effects of ginsenoside Rg1 on cerebral angiogenesis as well as its underlying mechanisms. Mice were subjected to treatment with vehicle or ginsenoside Rg1 daily for 14 d beginning at 24 h after distal middle cerebral artery occlusion (dMCAO). Compared with the dMCAO group, ginsenoside Rgl improved the neurobehavioral outcomes and reduced the brain infarct volume. Ginsenoside Rg1 treatment increased the expression of the cluster of differentiation 31 (CD31), bromodeoxyuridine(+) /CD31(+) microvessels and GFAP-positive vessels in the peri-infarct cortex. The expression of VEGF was significantly enhanced in ginsenoside Rg1 group. In vitro, human brain microvascular endothelial (hCMEC/D3) cells was successfully cultured, and oxygen and glucose deprivation (OGD) model was established. Ginsenoside Rg1 significantly increased proliferation, migration and tube formation of endothelial cells after OGD, as well as upregulated the expressions of VEGF, HIF-1 alpha, PI3K, p-Akt, and p-mTOR. Furthermore, administration of PI3K/Akt/mTOR signaling pathway inhibitor LY294002 abolished the beneficial effects of ginsenoside Rg1. In conclusion, ginsenoside Rg1 promoted cerebral angiogenesis through increasing the expression of VEGF via PI3K/Akt/mTOR signaling pathway after ischemic stroke.