中国药理学与毒理学杂志2024，Vol.38Issue(11)：807-815,9.DOI:10.3867/j.issn.1000-3002.2024.11.001
盐酸羟哌吡酮(YL-0919)通过抑制铁死亡改善大鼠缺血性脑卒中
Hypidone hydrochloride(YL-0919)improves ischemic stroke in rats by inhibiting ferroptosis
摘要
Abstract
OBJECTIVE To study the way in which hypidone hydrochloride(code:YL-0919)improves motor function after ischemic stroke(IS)and explore the related mechanism.METHODS Adult male SD rats were used to establish a middle cerebral artery occlusion(MCAO)model that simulated acute IS.All animals were randomly divided into four groups:sham group,MCAO group,MCAO+YL-0919 group,and MCAO+YL-0919+erastin(Era,ferroptosis inducer)group.The drug administration groups received the first ip injection 6 h after operation,followed by continuous ip injection once per day.After 7-10 d of drug administration,the effect of YL-0919 on motor function after IS were evaluated via neu-rological function test,adhesive-removal test,rotarod test,balance beam test and open field test.After 7 d of drug administration,TTC staining was used to detect the cerebral infarction area while the colo-rimetry method was used to measure the contents of glutathione(GSH),malondialdehyde(MDA),and ferrous ions(Fe2+)in the penumbra of the cerebral cortex.Western blotting was used to detect the expression levels of glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(xCT),acyl-CoA synthetase long-chain family member 4(ACSL4),and transferrin receptor 1(TFR1)in the cortical penumbra.RESULTS Compared with the sham group,the MCAO group showed higher neurological function scores(P<0.01),with notably prolonged time for tape removal and first contact with the right forepaw(P<0.01),spent significantly more time crossing the balance beam(P<0.01)but endured a notably shorter duration on the rotarod(P<0.01),reduced the movement distance in the open field(P<0.01),had a remarkably increased infarct area(P<0.01)but significantly level of GSH in the cortical penumbra region decreased(P<0.01),while MDA and Fe2+levels were markedly increased(P<0.01).Protein expression levels of GPX4 and xCT were reduced(P<0.05),while those of ACSL4 and TFR1 were elevated(P<0.05).Compared with the MCAO group,these changes were significantly reversed after YL-0919 administration.However,when Era and YL-0919 were administered simultaneously,the reversal effect of YL-0919 was significantly weakened.CONCLUSION YL-0919 can improve motor function impairment and reduce cerebral infarction areas in rats after IS,and the mechanism may be related to the inhibition of ferroptosis.关键词
盐酸羟哌吡酮(YL-0919)/缺血性脑卒中/运动功能/铁死亡Key words
hypidone hydrochloride(YL-0919)/ischemic stroke/motor function/ferroptosis分类
医药卫生引用本文复制引用
侯晓娟,张悦,白亚璠,李海龙,杨艺歆,李云峰,麻慧,王恒林..盐酸羟哌吡酮(YL-0919)通过抑制铁死亡改善大鼠缺血性脑卒中[J].中国药理学与毒理学杂志,2024,38(11):807-815,9.基金项目
国家自然科学基金(82204360) （82204360）
国家科技创新2030重大专项(2021ZD0200900) National Natural Science Foundation of China(82204360) （2021ZD0200900）
and National Science and Technology Innovation 2030 Major Program(2021ZD0200900) （2021ZD0200900）
