Abstract: Objective To investigate the effects of furosemide(FUR) on PERK/eIF2α/CHOP pathway and secondary brain injury in rats with intracerebral hemorrhage (ICH). Methods The rats were divided into sham operation group, model group(intracerebral injection of collagenase type Ⅳ in ICH), furosemide low dose (FUR-L) groups, medium dose (FUR-M) groups,high dose (FUR-H) groups and ganglioside group, with eighteen rats in each. After treatment, the neurological function was evaluated and scored by Longa and the water content of brain tissue was measured; Evans blue extravasation test was used to detect the blood-brain barrier injury; HE staining microscopy was used to detect the damage of hippocampus neurons; enzyme-linked immunosorbent assay (ELISA) was used to detect the serum level 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, Longa score, Evans blue exudation, brain water content, level of serum IFN-γ and IL-6,the expression of p-PERK/PERK, p-eIF2α/eIF2α and CHOP were all significantly increased (P＜0.05). Compared with those in the model group, The morphological changes of hippocampal neurons in the FUR-L, FUR-M and FUR-H groups and ganglioside group were restored to different degrees and the pathological damage was alleviated, Longa score, brain water content, Evans blue exudation, level of serum IFN-γ and IL-6, expression of p-PERK/PERK, p-eIF2α/eIF2α and CHOP were decreased (P＜0.05). Conclusions Furosemide can down-regulate the expression of PERK/eIF2α/CHOP pathway protein, relieve brain edema and hippocampal neuron damage and repair the neural function in ICH animal.model.

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