首页> 美国卫生研究院文献>International Journal of Biological Sciences >Lyophilized Powder of Catalpol and Puerarin Protected Cerebral Vessels from Ischemia by Its Anti-apoptosis on Endothelial Cells
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Lyophilized Powder of Catalpol and Puerarin Protected Cerebral Vessels from Ischemia by Its Anti-apoptosis on Endothelial Cells

机译:梓醇和葛根素冻干粉对血管内皮细胞的抗凋亡保护作用。

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摘要

Catalpol and puerarin are two monomers of Rehmannia glutinosa and Lobed Kudzuvine Root, which are two herbs commonly used together in ancient prescriptions of traditional Chinese medicine for cerebral ischemia. Our previous study shows that the lyophilized powder of the two monomers improved the outcome of cerebral ischemia excellently in rodents. However, if it protects vessels from ischemia is unknown. The present research studied the protection of lyophilized powder of catalpol and puerarin (CP) on endothelial cells and the relative mechanism in vivo and in vitro. Middle cerebral artery occlusion (MCAO) rats were used to study the improvement of CP on neurological deficiency, regional cerebral blood flow (rCBF), and infarct volume. The morphology of vessels and the apoptosis of brain vascular endothelial cells (BVECs) were observed and detected by immunohistochemistry approaches. To study how CP protected primary BVECs (pBVECs) from ischemic penumbra, oxygen glucose deprivation (OGD)-damaged pBVECs were cultured in the condition of insufficient nutrition and low oxygen which recapitulate the low perfusion of ischemic penumbra. Using the cell model, the mechanism by which CP protected pBVECs was studied by shRNA and pathway inhibitors. CP at the dose of 65.4 mg/kg increased regional cerebral blood flow (rCBF), reduced infarct volume, protected vessel integrity and inhibited endothelial cell apoptosis in vivo. But it only improved rCBF, vessel integrity and BVECs apoptosis at the dose of 32.7 mg/kg. In vitro, the protection of CP on pBVECs was proved to be ERK/HIF-1a- and PI3K/AKT/mTOR/HIF-1a-dependent. This study indicates a possibility of CP being a new drug for cerebral ischemia. Besides, this research provides an alternative cell model for penumbra ECs study.
机译:Catalpol和葛根素是熟地黄和Lobed Kudzuvine根的两种单体,这两种草药在古代中医脑缺血处方中通常一起使用。我们以前的研究表明,两种单体的冻干粉可以很好地改善啮齿动物的脑缺血结局。但是,是否可以保护血管免受缺血尚不清楚。本研究研究了梓醇和葛根素冻干粉对内皮细胞的保护作用及其体内外相关机制。使用大脑中动脉闭塞(MCAO)大鼠研究CP对神经系统缺陷,局部脑血流量(rCBF)和梗塞体积的改善。免疫组织化学方法观察和检测血管的形态和脑血管内皮细胞(BVECs)的凋亡。为了研究CP如何保护原发性BVEC(pBVEC)免受缺血性半影​​,在营养不足和低氧的情况下培养了缺氧缺氧(OGD)受损的pBVEC,从而再现了缺血性半影​​的低灌注。使用细胞模型,通过shRNA和途径抑制剂研究了CP保护pBVEC的机制。 65.4 mg / kg剂量的CP在体内可增加局部脑血流量(rCBF),减少梗塞体积,保护血管完整性并抑制内皮细胞凋亡。但它仅以32.7 mg / kg的剂量改善了rCBF,血管完整性和BVEC的细胞凋亡。在体外,证明CP对pBVEC的保护是ERK / HIF-1a和PI3K / AKT / mTOR / HIF-1a依赖性的。该研究表明CP可能是脑缺血的新药。此外,该研究为半影ECs研究提供了另一种细胞模型。

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