关键词: 呋塞米, 脑出血, PERK/eIF2α/CHOP通路, 脑损伤

Abstract: Objective: To investigate the effects of furosemide on PERK/eIF2α/CHOP pathway and secondary brain injury in rats with intracerebral hemorrhage (ICH). Methods: ICH rat model was established by intracerebral injection of collagenase type IV, and the rats were randomly divided into model group, low-dose furosemide group, medium dose furosemide group, high-dose furosemide group and ganglioside group, with eighteen rats in each group, another eighteen SD rats were selected as sham operation group. After drug treatment, the neurological deficits of rats in each group were scored; the water content of brain tissue was measured; Evans blue extravasation test was used to detect the blood-brain barrier injury; HE staining was used to detect the damage of hippocampal neurons; enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of interferon-γ (IFN-γ) and interleukin-6 (IL-6); Western blot was used to detect the expression of p-PERK/PERK, p-eIF2α/eIF2α and CHOP. Results: Compared with those in the sham operation group, the hippocampal neurons in the model group were degenerated and necrotic, the shrinkage was smaller, the number was significantly decreased, severe pathological damage was found, the neurological deficit score, brain water content, Evans blue exudation, levels of serum IFN-γ and IL-6, expression levels of p-PERK/PERK, p-eIF2α/eIF2α and CHOP were significantly increased (P < 0.05). Compared with those in the model group, the pathological damage of hippocampal neurons in the low, medium and high dose furosemide groups and ganglioside group were reduced, the neurological deficit score, brain water content, Evans blue exudation, levels of serum IFN-γ and IL-6, expression levels of p-PERK/PERK, p-eIF2α/eIF2α and CHOP were decreased (P < 0.05), furosemide groups were dose-dependent, and there was no significant change in each index between furosemide high-dose group and ganglioside group (P > 0.05). Conclusion: Furosemide can down-regulate the expression of PERK/eIF2α/CHOP pathway protein, relieve brain edema and hippocampal neuron damage, and repair the neural function of ICH rats.

Key words: furosemide, intracerebral hemorrhage, PERK/eIF2α/CHOP pathway, brain injury