摘要
目的:通过研究应用依达拉奉前后JNK通路及自噬因子Beclin-1、LC3-Ⅱ表达的变化,探讨依达拉奉对蛛网膜下腔出血(SAH)大鼠海马区c-Jun氨基端激酶(JNK)-自噬通路的影响。方法:选取雄性清洁级健康SD大鼠(350~450 g),随机分为假手术组(Sham组)、SAH模型组(SAH组)、SAH应用JNK抑制剂组(SP600125组)、SAH联合应用依达拉奉干预组(Edaravone组)。利用颅内动脉穿刺法制成大鼠SAH模型,SP600125组于造模前30 min,利用立体定向仪行侧脑室注射SP600125溶液;Edaravone组在建模成功后予以依达拉奉干预治疗。利用H-E染色观察每组大鼠海马区神经元形态及数量变化;应用免疫组织化学显色检测p-JNK以及自噬标志物Beclin-1和LC3-Ⅱ在大鼠海马区的表达情况。结果:与Sham组比较,SAH组在各时间点海马区神经元存活数量减少,与SAH组比较,SP600125组和Edaravone组正常形态细胞数量明显增多;SAH组大鼠海马区Beclin-1、LC3-Ⅱ阳性细胞数量多于Sham组,且均在24 h达到高峰,与SAH组比较,SP600125组和Edaravone组海马区Beclin-1、LC3-Ⅱ阳性细胞数均显著减少;与Sham组比较,SAH组大鼠海马区p-JNK阳性细胞数量明显增加,与SAH组比较,SP600125组和Edaravone组海马区p-JNK阳性细胞数均显著减少。结论:依达拉奉可抑制SAH后海马区JNK信号过度激活,降低自噬激活的程度,从而对SAH后海马区神经元细胞起到保护作用。
Objective： To explore the effect of edaravone on autophagy of hippocampal neural ceils in subarachnoid hemorrhage （SAH） rats. Methods： SD rats were randomly divided into sham operating group, SAH group, and JNK inhibitor group and edaravone group. Rats in JNK inhibitor groups received SP600125 solution through the lateral ventricle 30 min before modeling. And, animals in edaravone group received intraperitoneal edaravone （5 ntg/kg） after modeling and once again 12 hours later until the rats were sacrificed. Morphological characteristics and immunochemical expressions of p-JNK, Beclin-1 and LC3-H of neural cells in hippocampus were detected. Results： Compared to sham rats, the survival neurons were statistically lesser in SAH rats, companying with significant persistent upregulation of Beclin-1, LC3-Ⅱ and p-JNK, which reached their peaks at 24 h. And, the reduced neurons caused by hemorrhage were reversed significantly owing to administration of JNK inhibitor SP600125 and intraperitoneal edaravone, companying with statistical downregulation of Beclin 1, LC3-Ⅱ and p-JNK Conclusion： Edaravone should hold potential against autophagy by inhibiting overactivation of JNK singling, thus protect the neurons in the hippocampus of SAH rats.
作者
赵雅宁
刘瑶
周娜
徐继伟
李建民
Zhao Yaning Liu Yao Zhou Na Xu Jiwei Li Jianmin(College of Nursing and Rehabilitation College of Clinical Medicine Neurosurgery Department of Affliated Hospital, North China University of Science and Technology, Tangshan 063000, China)
出处
《解剖学杂志》
CAS
CSCD
北大核心
2017年第1期40-43,F0002,共5页
Chinese Journal of Anatomy
