The alpha2-adrenergic receptor agonist clonidine protects against cerebral ischemia/reperfusion induced neuronal apoptosis in rats.

Autor: He Z; Department of Pharmacology, College of Medicine, Jiaxing University, 314001, Jiaxing, People's Republic of China. hezhi@ctgu.edu.cn.; Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, 443002, Yichang, People's Republic of China. hezhi@ctgu.edu.cn.; College of Basic Medical Sciences, China Three Gorges University, 443002, Yichang, People's Republic of China. hezhi@ctgu.edu.cn., Yin BK; Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, 443002, Yichang, People's Republic of China.; Yichang Yiling Hospital, 443000, Yichang, People's Republic of China.; Zhongnan Hospital of Wuhan University, 430071, Wuhan, People's Republic of China., Wang K; Department of Pharmacology, College of Medicine, Jiaxing University, 314001, Jiaxing, People's Republic of China., Zhao B; Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, 443002, Yichang, People's Republic of China.; College of Basic Medical Sciences, China Three Gorges University, 443002, Yichang, People's Republic of China., Chen Y; Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, 443002, Yichang, People's Republic of China.; College of Basic Medical Sciences, China Three Gorges University, 443002, Yichang, People's Republic of China., Li ZC; Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, 443002, Yichang, People's Republic of China. zichengli@ctgu.edu.cn.; College of Basic Medical Sciences, China Three Gorges University, 443002, Yichang, People's Republic of China. zichengli@ctgu.edu.cn., Chen J; Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, 443002, Yichang, People's Republic of China. chenjing@ctgu.edu.cn.; College of Medicine and Health Sciences, China Three Gorges University, No.8 Daxue Road, 443002, Yichang, People's Republic of China. chenjing@ctgu.edu.cn.
Jazyk: angličtina
Zdroj: Metabolic brain disease [Metab Brain Dis] 2024 Jun; Vol. 39 (5), pp. 741-752. Date of Electronic Publication: 2024 Jun 04.
DOI: 10.1007/s11011-024-01354-3
Abstrakt: Apoptosis is the crucial pathological mechanism following cerebral ischemic injury. Our previous studies demonstrated that clonidine, one agonist of alpha2-adrenergic receptor (α2-AR), could attenuate cerebral ischemic injury in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). However, it's unclear whether clonidine exerts neuroprotective effects by regulating neuronal apoptosis. In this study, we elucidated whether clonidine can exert anti-apoptotic effects in cerebral ischemic injury, and further explored the possible mechanisms. Neurological deficit score was measured to evaluate the neurological function. TTC staining was used for the measurement of brain infarct size. Hematoxylin-Eosin (HE) staining was applied to examine the cell morphology. TUNEL and DAPI fluorescent staining methods were used to analyze the cell apoptosis in brain tissue. Fluorescence quantitative real-time PCR was performed to assess the gene expression of Caspase-3 and P53. Western blotting assay was applied to detect the protein expression of Caspase-3 and P53. The results showed that clonidine improved neurological function, reduced brain infarct size, alleviated neuronal damage, and reduced the ratio of cell apoptosis in the brain with MCAO/R injury. moreover, clonidine down-regulated the gene and protein expression of Caspase-3 and P53 which were over-expressed after MCAO/R injury. Whereas, yohimbine (one selective α2-AR antagonist) mitigated the anti-apoptosis effects of clonidine, accompanied by reversed gene and protein expression changes. The results indicated that clonidine attenuated cerebral MCAO/R injury via suppressing neuronal apoptosis, which may be mediated, at least in part, by activating α2-AR.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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