Mechanism of butylphthalide activating cAMP/CREB/BDNF signaling to improve cognitive impairment after ischemia-reperfusion in mice

doi:10.12092/j.issn.1009-2501.2019.02.006

Abstract

Abstract:

AIM: To study the mechanism of butylphthalide to improve the cognitive impairment after ischemia-reperfusion in mice by stimulating cAMP/CREB/BDNF signal and to provide support for the study of butylphthalide. METHODS: The cognitive impairment model （VCI）was induced by repeated ligation of bilateral common carotid arteries in mice with ischemia-reperfusion injury. The mice were divided into sham operation group, model group and drug group. The drug group was treated with 5, 10, 20 mg/kg butylphthalide (NBP). The Morris water maze test was used to detect the cognitive ability of mice. Nissl staining was used to observe the morphology of neurons in the hippocampus of mice. The activity of SOD, the level of malondialdehyde (MDA) and nitric oxide (NO) were detected by colorimetric method. The expression of cyclic adenosine phosphate (cAMP), phosphorylated cyclic phosphoric acid (p-CREB) and brain derived neurotrophic factor (BDNF) in the hippocampus were detected by Western blot. RESULTS:Compared with the sham operation group, the cognitive function of the model group was decreased (P<0.05), the SOD expression level in the hippocampus tissue of the model group was decreased, and the levels of MDA and NO were increased (P<0.05), and Nissl staining showed that the neuron cell degeneration and necrosis were found in the model group and the expression of cAMP/CREB/BDNF signal was inhibited (P<0.05). Compared with the model group, after NBP intervened, the cognitive ability of mice was significantly improved (P<0.05), the level of SOD in hippocampus was up-regulated, and the levels of MDA and NO were decreased in a dose-dependent manner (P<0.05). The cAMP/CREB/BDNF signal activated the expression of key proteins cAMP, p-CREB and BDNF increased. Nissl staining showed that the apoptosis of neurons in hippocampus was reduced after NBP intervention. CONCLUSION: NBP can activate cAMP/CREB/BDNF signal to improve cognitive function after ischemia and reperfusion, which is one of the mechanisms of butylphthalide improvement of cognitive impairment after stroke.

Key words: butylphthalide, ischemia-reperfusion, cognitive impairment, cyclic adenosine, phosphorylated cyclic adenosine reaction original binding protein, brain derived neurotrophic factor

CLC Number:

R965.2

GUAN Qiaobing, HAN Chenyang, CHU Zhiyuan, YANG Yi, ZHANG Xiaoling. Mechanism of butylphthalide activating cAMP/CREB/BDNF signaling to improve cognitive impairment after ischemia-reperfusion in mice[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(2): 152-157.

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