An in vivo study of hypoxia-inducible factor-1α signaling in ginsenoside Rg1-mediated brain repair after hypoxia/ischemia brain injury
An in vivo study of hypoxia-inducible factor-1α signaling in ginsenoside Rg1-mediated brain repair after hypoxia/ischemia brain injury
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DOI：
10.1038/pr.2016.178
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发表时间：
2017
影响因子：
3.6
通讯作者：
Binzhi Tang;Dejian Wang;Mao-jun Li;Qing Wu;Qian Yang;Wei Shi;Chang-hui Chen
中科院分区：
文献类型：
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作者：
Binzhi Tang;Dejian Wang;Mao-jun Li;Qing Wu;Qian Yang;Wei Shi;Chang-hui Chen
背景：缺氧缺血性脑损伤是新生儿常见的中枢神经系统损伤。研究已经证明了HPLC-Rg 1在增加神经活力和促进血管生成方面的生物活性。方法：采用改良的Rice-Vannucci模型（Rice-Vannucci model，RVM）建立新生儿HI模型，分别给予Rg 1或单唾液酸四己糖神经节苷脂（monosialotetrahexosyl ganglioside，GM 1）治疗。观察大鼠神经功能和病理学变化。TUNEL法检测细胞凋亡;血管性血友病因子（vwf）的免疫组化标记微血管。结果：Rg 1和GM 1均能通过提高神经元存活率，减轻HI后神经功能缺损和病理损伤。Rg 1也能促进HI后的血管生成，而GM 1则无此作用。结论：Rg 1在新生儿HI脑损伤中具有神经保护作用，HIF-1α可能是治疗新生儿HI脑损伤的潜在靶点。
Background:Hypoxia/ischemia (HI) brain injury is a common central nervous system insult in newborns. Studies have demonstrated bioactivity of ginsenoside Rg1 in increasing neural viability and promoting angiogenesis. However, there are few reports on roles of Rg1 in brain repair of neonatal HI, and the mechanisms involved are unclear.Methods:a neonatal HI model was established by a modified Rice-Vannucci model (RVM) and pups received ginsenoside Rg1 or monosialotetrahexosyl ganglioside (GM1) treatment. Neurological function and pathologic damage of rats were evaluated. Cellular apoptosis was detected with Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Immunohistochemistry for von willebrand factor (vwf) was used to label micro vessels. Expression levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and cleaved caspase 3 (CC3) were detected by western blot.Results:Both Rg1 and GM1 reduced neurological impairment and pathologic damage after HI by enhancing neural survival. Rg1, but not GM1, could also facilitate angiogenesis after HI. These pharmacological effects of Rg1 may be attributed to regulation of expression level of VEGF and CC3 and HIF-1α signaling pathway was involved.Conclusion:Rg1 plays a neuroprotective role in brain repair following neonatal HI, and HIF-1α is a potential target for therapeutic intervention in neonates with HI brain injury.