Effects of chrysophanol on HIF-1α and VEGF expressions in mice with focal cerebral ischemia/reperfusion injury

doi:10.3969/j.issn.1006-7795.2021.02.010

Abstract

Abstract: Objective To investigate the effects of chrysophanol (CHR) on the expressions of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in the penumbra of focal cerebral ischemia/reperfusion mice and further, to explore the long-term protective effect mechanism of CHR against cerebral ischemia/reperfusion injury.Methods According to the random number table, 18 healthy male 2-month-old C57BL mice were divided into 3 groups: sham operation (Sham) group (n=6), middle cerebral artery occlusion (MCAO) group (n=6), and CHR group (CHR in dose of 0.1 mg/kg was intraperitoneally injected in CHR group mice once a day for 14 days after reperfusion, n=6). The MCAO for 45 min was induced by thread embolism and the reperfusion lasted for 14 days. On the 14th day after reperfusion, the brain tissue was obtained. The expressions of HIF-1αand VEGF in the brain ischemic penumbra were observed with immunofluorescence labeling. The colocalization of HIF-1α or VEGF with neuron marker NeuN was determined with double labeling immunofluorescence. Results 1) There was little HIF-1α positive cell in Sham group. Compared with Sham group, the HIF-1α positive cells in the penumbra of MCAO group obviously increased on the 14th day after reperfusion (P<0.05). Compared with MCAO group, the HIF-1α positive cells decreased significantly in the penumbra of CHR group on the 14th day after reperfusion (P<0.05). 2) There were many VEGF positive cells in Sham group. Compared with Sham group, the VEGF positive cells in the penumbra of MCAO group obviously decreased on the 14th day after reperfusion (P<0.05). Compared with MCAO group, the VEGF positive cells increased significantly in the penumbra of CHR group on the 14th day after reperfusion (P<0.05). 3) In the penumbra of ischemic brain of mice, HIF-1α or VEGF was colocalized with neuron marker NeuN, respectively. Conclusion CHR may inhibit the expression of HIF-1α protein, upregulate the expression of VEGF protein, and reduce neuronal damage, thereby exerting long-term neuroprotection against cerebral ischemia-reperfusion injury.

Key words: chrysophanol, cerebral ischemia/reperfusion, hypoxia inducible factor-1α, vascular endothelial growth factor

CLC Number:

R743.3

Fang Yalan, Yang Nan, Zhao Yongmei, Huang Yuyou, Li Jincheng, Duan Yunxia, Gao Li, Luo Yumin. Effects of chrysophanol on HIF-1α and VEGF expressions in mice with focal cerebral ischemia/reperfusion injury[J]. Journal of Capital Medical University, 2021, 42(2): 219-224.

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URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2021.02.010

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2021/V42/I2/219

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