Jang Hyunduk, Oh Mi-Young, Kim Young-Ju, Choi In-Young, Yang Hye Sung, Ryu Wi-Sun, Lee Seung-Hoon, Yoon Byung-Woo
Neuroscience Research Institute in SNUMRC, Seoul National University, Seoul, Republic of Korea; Department of Neurology, Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
J Neurosci Res. 2014 Nov;92(11):1520-8. doi: 10.1002/jnr.23427. Epub 2014 Jun 17.
Hydrogen sulfide (H2 S) is a potent vasodilator and regulates cardiovascular homeostasis. Furthermore, H2 S has a crucial role in ischemia-reperfusion injuries, especially of the heart, liver, and kidneys. This study indicates that treatment with hydrogen sulfide is able to restore neurological function after ischemic stroke by promoting angiogenesis. Treatment with H2 S augments angiogenesis in the peri-infarct area, and it significantly improves functional outcomes after 2 weeks in a rat MCAO model. H2 S promotes the phosphorylation of AKT and ERK and increases the expression of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1). H2 S-treated rats showed more newly synthesized endothelial cells in the ischemic lesion (2.31-fold, P < 0.01). H2 S-treated astrocytes increased VEGF and Ang-1 expression, and the inhibition of phosphatidylinositide 3-kinase (PI3K)/AKT signaling by LY294002 significantly reduced H2 S-induced VEGF and Ang-1 expression in astrocytes. Finally, H2 S stimulated endothelial cell migration (3.92-fold increase in wound healing assay) and tube formation (3.69-fold increase, P < 0.001) through PI3K/AKT signaling. In conclusion, treatment with H2 S promotes angiogenesis and thereby contributes to improvement of functional outcome after cerebral ischemia. Our findings strongly suggest that H2 S may be of value in regenerative recovery after stroke.
硫化氢（H₂S）是一种强效血管舒张剂，可调节心血管稳态。此外，H₂S在缺血再灌注损伤中，尤其是心脏、肝脏和肾脏的缺血再灌注损伤中起着关键作用。本研究表明，硫化氢治疗能够通过促进血管生成来恢复缺血性中风后的神经功能。在大鼠大脑中动脉闭塞（MCAO）模型中，用H₂S治疗可增加梗死周围区域的血管生成，并在2周后显著改善功能结局。H₂S促进AKT和ERK的磷酸化，并增加血管内皮生长因子（VEGF）和血管生成素-1（Ang-1）的表达。经H₂S治疗的大鼠在缺血性病变中显示出更多新合成的内皮细胞（增加2.31倍；P<0.01）。经H₂S处理的星形胶质细胞增加了VEGF和Ang-1的表达，而LY294002对磷脂酰肌醇3激酶（PI3K）/AKT信号通路的抑制显著降低了H₂S诱导的星形胶质细胞中VEGF和Ang-1的表达。最后，H₂S通过PI3K/AKT信号通路刺激内皮细胞迁移（伤口愈合试验中增加3.92倍）和管腔形成（增加3.69倍；P<0.001）。总之，H₂S治疗可促进血管生成，从而有助于改善脑缺血后的功能结局。我们的研究结果强烈表明，H₂S可能对中风后的再生恢复具有重要价值。
