Hypidone hydrochloride(YL-0919)improves ischemic stroke in rats by inhibiting ferroptosis
10.3867/j.issn.1000-3002.2024.11.001
- VernacularTitle: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
- Author:
Xiaojuan HOU
1
,
2
;
Yue ZHANG
;
Yafan BAI
;
Hailong LI
;
Yixin YANG
;
Yunfeng LI
;
Hui MA
;
Henglin WANG
Author Information
1. 河北北方学院研究生院,河北 张家口 075000
2. 解放军总医院第六医学中心麻醉科,北京 100048
- Keywords:
hypidone hydrochloride(YL-0919);
ischemic stroke;
motor function;
ferroptosis
- From:
Chinese Journal of Pharmacology and Toxicology
2024;38(11):807-815
- CountryChina
- Language:Chinese
-
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.
