Abstract

Neonatal hypoxic-ischemic encephalopathy (HIE) is a devastating condition that affects neurodevelopment and results in brain injury in infants. Morroniside (MOR), a natural secoiridoid glycoside, has been found to possess neuroprotective effect. However, the effects of MOR on neonatal HIE are unclear. An in vitro HIE model was established in murine hippocampal neurons HT-22 cells using oxygen-glucose deprivation/reoxygenation (OGD/R) stimulation. Our results showed that MOR improved OGD/R-caused cell viability reduction in HT-22 cells. MOR suppressed the production of reactive oxygen species (ROS) and malondialdehyde (MDA) in OGD/R-induced HT-22 cells in a dose-dependent manner. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GP_X) were significantly elevated by MOR. Moreover, MOR treatment caused a significant increase in bcl-2 expression, and obvious decreases in the expression levels of bax, cleaved caspase-3, and cleaved caspase-9 expression. Furthermore, MOR significantly upregulated the expression levels of nuclear Nrf2 and HO-1 in OGD/R-treated HT-22 cells. Additionally, knockdown of Nrf2 or HO-1 abrogated the effects of MOR on OGD/R-induced oxidative stress and apoptosis in HT-22 cells. In conclusion, these findings suggested that MOR protects HT-22 cells against OGD/R via regulating the Nrf2/HO-1 signaling pathway.

摘要

新生儿缺氧缺血性脑病 (HIE) 是一种破坏性疾病，会影响神经发育并导致婴儿脑损伤。Morroniside (MOR) 是一种天然的类环烯醚萜苷，已被发现具有神经保护作用。然而，MOR 对新生儿 HIE 的影响尚不清楚。使用氧-葡萄糖剥夺/复氧 (OGD/R) 刺激在小鼠海马神经元 HT-22 细胞中建立了体外HIE 模型。我们的结果表明，MOR 改善了 OGD/R 引起的 HT-22 细胞中的细胞活力降低。MOR 以剂量依赖性方式抑制 OGD/R 诱导的 HT-22 细胞中活性氧 (ROS) 和丙二醛 (MDA) 的产生。超氧化物歧化酶 (SOD) 和谷胱甘肽过氧化物酶 (GP _{X ) 的活性}) MOR 显着升高。此外，MOR 处理导致 bcl-2 表达显着增加，而 bax、cleaved caspase-3 和 cleaved caspase-9 的表达水平明显降低。此外，MOR 显着上调 OGD/R 处理的 HT-22 细胞中核 Nrf2 和 HO-1 的表达水平。此外，Nrf2 或 HO-1 的敲低消除了 MOR 对 OGD/R 诱导的 HT-22 细胞氧化应激和细胞凋亡的影响。总之，这些发现表明，MOR通过调节 Nrf2/HO-1 信号通路保护 HT-22 细胞免受 OGD/R 影响。