法舒地尔对蛛网膜下腔出血大鼠铁死亡的影响  

Effect of fasudil on neuronal ferroptosis in rats with subarachnoid hemorrhage

作　　者：孙林林 马玉德[1] 张朋垒 焦继超[1] 李富姣 李志营[2] 王艺博 孟方方 邵彩霞[4] Sun Linlin;Ma Yude;Zhang Penglei;Jiao Jichao;Li Fujiao;Li Zhiying;Wang Yibo;Meng Fangfang;Shao Caixia(Department of Neurosurgery,Zhengzhou Seventh People's Hospital,Zhengzhou 450000,Henan Province,China)

机构地区：[1]郑州市第七人民医院神经外科,450000 [2]郑州市第七人民医院医务科,450000 [3]郑州市第七人民医院急诊科,450000 [4]郑州市第七人民医院手术室,450000 [5]青岛市第六人民医院感染科

出　　处：《中华老年心脑血管病杂志》2022年第10期1094-1097,共4页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：河南省医学科技攻关计划项目(LHGJ20210744,LHGJ20210755)。

摘　　要：目的探索法舒地尔(Fasudil)对蛛网膜下腔出血(subarachnoid hemorrhage,SAH)大鼠铁死亡的影响。方法24只SD大鼠按随机数字表法分为假手术组(Sham组,n=8)、SAH组(n=8)、SAH+Fasudil组(Fasudil组,n=8)。颈内动脉刺破法造SAH模型。Fasudil组造模后腹腔注射Fasudil(10 mg/kg 1次/12 h)。造模成功24 h后观察大鼠神经功能(Garcia JH评分及穿梭箱试验),检测脑组织Fe^(2+)浓度,免疫组织化学染色、Western blot检测谷胱甘肽过氧化物酶4(GPX4)及长链脂酰辅酶A合成酶4(ACSL4)蛋白的表达。结果与Sham组比较,SAH组大鼠Garcia JH评分显著降低,海马区脑组织中Fe^(2+)含量显著增高,GPX4表达明显减少,ACSL4蛋白表达明显增高,差异有统计学意义(P<0.05)。与SAH组比较,Fasudil组大鼠Garcia JH评分增高[(13.88±3.94)分vs(10.13±4.39)分,P<0.05],海马区脑组织中Fe^(2+)含量显著降低[(0.069±0.023)nmol/mg vs(0.098±0.051)nmol/mg,P<0.05],GPX4表达显著增高[(47.63±7.74)个vs(22.13±7.12)个,P<0.05],ACSL4蛋白表达显著减少[(40.67±17.79)个vs(53.12±15.67)个,P<0.05]。Fasudil组大鼠GPX4/GAPDH蛋白表达水平显著高于SAH组,ACSL4/GAPDH蛋白表达水平显著低于SAH组,差异有统计学意义(P<0.05)。结论法舒地尔减轻铁死亡,改善了大鼠的神经功能。Objective To explore the effects of fasudil on ferroptosis in rats with subarachnoid hemorrhage(SAH).Methods A total of 24 Sprague-Dawley rats were randomly and equally di-vided into sham group(n=8),SAH group(n=8),and Fasudil group(n=8).SAH model was es-tablished by puncturing the internal carotid artery in rats from the SAH group and Fasudil group.Fasudil(10 mg/kg q12 h)was injected intraperitoneally in the Fasudil group after model-ing.The neurological function of the rats was observed in 24 h after modeling(Garcia JH score and shuttle box test).The Fe^(2+)concentration in brain tissue was detected,and the expression of glutathione peroxidase 4(GPX4)and acyl-CoA synthetase long-chain family member 4(ACSL4)was detected by immunohistochemical staining and Western blotting.Results Compared with the Sham group,the neurological function was deteriorated,the Fe^(2+)content in the hippocampus was increased,the expression of GPX4 was decreased and that of ACSL4 was increased in the rats from the SAH group(P<0.05).The Fasudil group had significantly higher Garcia JH score(13.88±3.94 vs 10.13±4.39,P<0.05),reduced Fe^(2+)content in the hippocampus(0.069±0.023 nmol/mg vs 0.098±0.051 nmol/mg,P<0.05),enhanced GPX4 level(47.63±7.74 vs 22.13±7.12,P<0.05),and decreased ACSL4 expression level(40.67±17.79 vs 53.12±15.67,P<0.05)when compared with the SAH group.The expression level of GPX4/GAPDH protein was significantly increased while the protein expression level of ACSL4/GAPDH was decreased in the Fasudil group than the with SAH group(P<0.05).Conclusion Fasudil hydrochloride atten-uates ferroptosis and improves neurological function in rats.

关 键 词：蛛网膜下腔出血 细胞死亡 RHO相关激酶类 海马 

分 类 号：R965[医药卫生—药理学]