摘要
目的探讨外源性硫化氢(H2S)对蛛网膜下腔出血(SAH)大鼠早期脑损伤(EBI)的改善作用及相关机制。方法将36只SD大鼠随机分为假手术组、模型组和H2S供体-NaHS治疗组,每组12只。采用改良血管内穿刺法制作大鼠SAH模型;造模后2 h,治疗组大鼠按100μmol/kg剂量腹腔内注射2 mL NaHS溶液,假手术组及模型组大鼠均腹腔内注射等量生理盐水。造模24 h后,对各组大鼠进行神经行为学评估及脑含水量检测;采用苏木素-伊红(HE)染色检测海马组织病理学变化;采用分光光度计法检测海马组织中内源性H2S,以及氧化应激相关指标超氧化物歧化酶(SOD)、丙二醛(MDA)的水平;采用原位末端标记法(TUNEL)染色检测海马组织神经元凋亡情况;采用Western blot检测海马组织中硫氧还蛋白-1(TRX1)、硫氧还蛋白互作蛋白(TXNIP)以及凋亡相关因子Bcl-2、cleaved-caspase3的表达。结果与SAH模型组比较,NaHS治疗组大鼠神经行为学评分显著升高,脑含水量显著降低;海马组织的病理学损伤得到明显改善且内源性H2S、SOD水平显著升高,而MDA水平显著降低;海马神经元凋亡率显著降低;Trx1及Bcl-2蛋白表达水平显著增加,而TXNIP及cleaved-caspase3表达水平显著降低。结论外源性硫化氢可改善SAH大鼠早期脑损伤,这可能与激活海马组织硫氧还蛋白系统,进而降低氧化应激反应、抑制神经元凋亡有关。
Objective To investigate the effect of exogenous hydrogen sulfide(H2S)on early brain injury(EBI)in SAH rats and its related mechanisms.Methods 36 SD rats were randomly divided into sham operation group,model group and H2S donor-NaHS treatment group,with 12 rats in each group.Rat SAH model was established by modified intravascular puncture method.2 h after modeling,the treatment group rats were intraperitoneally injected with 2 mL NaHS at a dose of 100μmol/kg,and the sham group and model group rats were intraperitoneally injected with the same amount of normal saline.After 24 hours of modeling,neurobehavioral assessment and content of brain water were conducted in each group of rat.Hematoxylin-eosin(HE)staining was used to detect histopathological changes in the hippocampus.The levels of endogenous H2S,superoxide dismutase(SOD)and malondialdehyde(MDA)in hippocampus were measured by spectrophotometer method.The apoptosis of neurons in hippocampus was detected by TUNEL staining.Western blot was used to detect the expressions of thioredoxin-1(TRX1),thioredoxin interacting protein(TXNIP),and apoptosis-related factors Bcl-2 and cleaved-caspase3 in the hippocampus.Results Compared with SAH model group,NaHS treatment significantly increased neurobehavioral score and decreased the content of brain water.The pathological damage of hippocampus was significantly improved,and endogenous H2S and SOD levels were significantly increased,while MDA level was significantly decreased.The apoptosis rate of hippocampal neurons was significantly reduced.TRX1 and Bcl-2 protein expression levels were significantly increased,while TXNIP and cleaved-caspase3 protein expression levels were significantly decreased.Conclusion Exogenous hydrogen sulfide can improve the early brain injury of SAH rats,which may be related to the activation of the thioredoxin system in the hippocampus,thereby reducing the oxidative stress response and inhibiting the apoptosis of neurons.
作者
曾进
田密
成建
蒙迪
聂伟
ZENG Jin;TIAN Mi;CHENG Jian;MENG Di;NIE Wei(Internal Medicine-Neurology, The First Affiliated Hospital of Hunan College of traditional Chinese Medicine, Zhuzhou 412000, Hunan, China)
出处
《西部医学》
2021年第6期829-834,共6页
Medical Journal of West China
关键词
硫化氢
蛛网膜下腔出血
早期脑损伤
海马
硫氧还蛋白
Hydrogen sulfide
Subarachnoid hemorrhage
Early brain injury
Hippocampus
Thioredoxin
