Hypoxia inducible factor-1alpha mediates protection of DL-3-n-butylphthalide in brain microvascular endothelial cells against oxygen glucose deprivation-induced injury.
Studies have demonstrated that DL-3-n-butylphthalide can significantly alleviate oxygen glucose deprivation-induced injury of human umbilical vein endothelial cells at least partly associated with its enhancement on oxygen glucose deprivation -induced hypoxia inducible factor-1α expression. In this study, we hypothesized that DL-3-n-butylphthalide can protect against oxygen glucose deprivation-induced injury of newborn rat brain microvascular endothelial cells by means of upregulating hypoxia inducible factor-1α expression. MTT assay and Hoechst staining results showed that DL-3-n-butylphthalide protected brain microvascular endothelial cells against oxygen glucose deprivation-induced injury in a dose-dependent manner. Western blot and immunofluorescent staining results further confirmed that the protective effect was related to upregulation of hypoxia inducible factor-1α. Real-time RT-PCR reaction results showed that DL-3-n-butylphthalide reduced apoptosis by inhibiting downregulation of pro-apoptotic gene caspase-3 mRNA expression and upregulation of apoptosis-executive protease bcl-2 mRNA expression; however, DL-3-n-butylphthalide had no protective effects on brain microvascular endothelial cells after knockdown of hypoxia inducible factor-1α by small interfering RNA. These findings suggest that DL-3-n-butylphthalide can protect brain microvascular endothelial cells against oxygen glucose deprivation-induced injury by upregulating bcl-2 expression and downregulating caspase-3 expression though hypoxia inducible factor-1α pathway.
Department of Neurology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China.
Weihong
W
Yang
Department of Neurology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China.
Ling
L
Li
Department of Neurology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China.
Ruxun
R
Huang
Department of Neurology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China.
Zhong
Z
Pei
Department of Neurology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China.
Songjie
S
Liao
Department of Neurology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China.
Jinsheng
J
Zeng
DL-3-n-butylphthalide; apoptosis; brain microvascular endothelial cells; hypoxia inducible factor-1α