C-Type Natriuretic Peptide Ameliorates Vascular Injury and Improves Neurological Outcomes in Neonatal Hypoxic-Ischemic Brain Injury in Mice.
C-Type Natriuretic Peptide Ameliorates Vascular Injury and Improves Neurological Outcomes in Neonatal Hypoxic-Ischemic Brain Injury in Mice.
复制标题
C型利钠肽改善新生儿缺氧缺血性脑损伤小鼠的血管损伤和神经功能预后。
DOI：
10.3390/ijms22168966
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发表时间：
2021-08-20
影响因子：
5.6
通讯作者：
Ma Q
中科院分区：
文献类型：
--
作者：
Shen G;Hu S;Zhao Z;Zhang L;Ma Q
c型利钠肽（CNP）是存在于大脑中的一种重要的血管调节剂。我们之前的研究证明了CNP在新生儿缺氧缺血性脑损伤后的先天神经保护作用。在本研究中，我们通过体内和体外模型进一步探讨了CNP在脑血管病理中的作用。在新生小鼠HI脑损伤模型中，我们发现重组CNP在脑室内剂量依赖性地减少脑梗死面积。CNP可显著减少脑水肿和免疫球蛋白G （IgG）向脑组织外渗，提示CNP具有血管保护作用。此外，在初级脑微血管内皮细胞（BMEC）中，CNP剂量依赖性地保护BMEC存活和单层完整性免受氧-葡萄糖剥夺（OGD）。CNP的血管保护作用是由其先天受体NPR2和NPR3介导的，抑制NPR2或NPR3均可抵消CNP对HI损伤后IgG渗漏和OGD下BMEC存活的保护作用。重要的是，CNP可显著改善HI损伤后的脑萎缩和神经功能缺损。综上所述，本研究表明重组CNP通过其先天受体在新生儿HI脑损伤中发挥血管保护作用，提示其可能是治疗新生儿HI脑损伤的潜在治疗靶点。
C-type natriuretic peptide (CNP) is an important vascular regulator that is present in the brain. Our previous study demonstrated the innate neuroprotectant role of CNP in the neonatal brain after hypoxic-ischemic (HI) insults. In this study, we further explored the role of CNP in cerebrovascular pathology using both in vivo and in vitro models. In a neonatal mouse HI brain injury model, we found that intracerebroventricular administration of recombinant CNP dose-dependently reduces brain infarct size. CNP significantly decreases brain edema and immunoglobulin G (IgG) extravasation into the brain tissue, suggesting a vasculoprotective effect of CNP. Moreover, in primary brain microvascular endothelial cells (BMECs), CNP dose-dependently protects BMEC survival and monolayer integrity against oxygen-glucose deprivation (OGD). The vasculoprotective effect of CNP is mediated by its innate receptors NPR2 and NPR3, in that inhibition of either NPR2 or NPR3 counteracts the protective effect of CNP on IgG leakage after HI insult and BMEC survival under OGD. Of importance, CNP significantly ameliorates brain atrophy and improves neurological deficits after HI insults. Altogether, the present study indicates that recombinant CNP exerts vascular protection in neonatal HI brain injury via its innate receptors, suggesting a potential therapeutic target for the treatment of neonatal HI brain injury.
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