摘要
目的探讨盐酸法舒地尔对癫痫大鼠大脑海马神经元氧化应激及凋亡的保护作用。方法将30只SD大鼠随机分成3组,分别为对照组、癫痫模型组(模型组)和盐酸法舒地尔处理组(治疗组),每组10只。采用氯化锂-匹罗卡品诱发癫痫大鼠模型,造模成功后予盐酸法舒地尔10 mg·kg-1腹腔注射治疗,每天1次。采用HE和尼氏染色法观察各组海马组织和神经细胞形态变化,ELISA检测各组大脑海马组织活性氧(ROS)、超氧化物歧化酶1(SOD1)、谷胱甘肽(GSH)活性及丙二醛(MDA)含量的变化,Real-time PCR检测各组大鼠大脑海马组织Bcl-2及Caspase-3基因表达,Western blot检测各组海马中BCL-2及Caspase-3蛋白表达水平。结果 HE染色显示对照组和治疗组两侧海马无明显损伤,海马CA1区及门区细胞排列整齐,形态完整,模型组海马CA1及门区细胞排列不规则。尼氏染色结果显示治疗组两侧海马组织CA1区神经细胞计数增加(P<0.05)。ELISA检测结果显示治疗组较模型组相比海马组织SOD1和GSH活性增加,ROS和MDA含量降低(P<0.05);Realtime PCR和Western blot检测结果显示Caspase-3基因和蛋白表达减少,BCL-2基因和蛋白表达增加(P均<0.05)。结论盐酸法舒地尔抑制氧化应激和降低凋亡的发生,从而对癫痫大鼠脑组织起到抗氧化和抗凋亡作用,具有神经保护的作用。
Objective To investigate the protective effect of Fasudil hydrochloride on oxidative stress and apoptosis of Kainic acid-induced Epilepsy model of rat and the intervention effect of fasudil hydrochloride on the related functional changes. Methods Thirty SD rats were randomly divided into three groups: control group,epilepsy model group(model group)and fasudil hydrochloride treatment group(treatment group),with10 rats in each group. The epileptic rat model was induced by lithium pilocarpine chloride. After the model was established,fasudil hydrochloride was injected intraperitoneally once a day. The morphological changes of hippocampal tissues and nerve cells were observed by HE and Nissl’s staining. The activities of reactive oxygen species(ROS),superoxide dismutase-1(SOD1),glutathione(GSH)and malondialdehyde(MDA)were detected by ELISA. The expression of Bcl-2 and Caspase-3 in hippocampus was detected by real-time PCR. The expression levels of BCL-2 and Caspase-3 in hippocampus were detected by Western blot. Results HE staining showed that there was no obvious damage to both sides of the hippocampus in the control group and the treatment group,and the cells in the CA1 area and portal area of the hippocampus were arranged orderly and intact,while the cells in the CA1 and portal area of the hippocampus in the model group were arranged irregularly. Nissl’s staining results showed that the number of neurons in CA1 area of hippocampus increased in the treatment group(P<0.05). The results of ELISA showed that compared with the model group,the activities of SOD1 and GSH were increased,the contents of ROS and MDA were decreased(P<0.05);the expression of Caspase-3 gene and protein was decreased,and the expression of BCL-2 gene and protein was increased(P all< 0. 05). Conclusion The fasudil hydrochloride inhibits oxidative s tress and reduces the occurrence of apoptosis,thus it has a neuroprotective effect against oxidative stress and apoptotic on the brain tissue of epileptic in model rats.
作者
黄燕飞
黑常春
龚歆
任双来
李媛媛
HUANG Yanfei;HEI Changchun;GONG Xin;REN Shuanglai;LI Yuanyuan(Department of General Medicine,People’s Hospital of Ningxia Hui Autonomous Region,Yinchuan 750021,China;Department of Anatomy and Histology of Basic Medical School,Ningxia Medical University,Yinchuan 750004,China;Ningxia Key Laboratory of Craniocerebral Diseases,Yinchuan 750004,China)
出处
《宁夏医科大学学报》
2020年第8期770-775,共6页
Journal of Ningxia Medical University
基金
宁夏自然科学基金(NZ14165)。
关键词
大鼠
癫痫
盐酸法舒地尔
氧化应激
凋亡
rat
fasudil hydrochloride
hippocampus
oxidative stress
apoptosis
