雷帕霉素对蛛网膜下腔出血大鼠脑损伤的保护作用  

Protective effect of rapamycin on brain injury in rats with subarachnoid hemorrhage

作　　者：曹齐 李文杰 王强[1] 陈原 Cao Qi;Li Wenjie;Wang Qiang;Chen Yuan(Department of Pharmacy,Xinhua Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200092,China)

机构地区：[1]上海交通大学医学院附属新华医院药学部,上海2000922

出　　处：《脑与神经疾病杂志》2025年第2期110-114,共5页Journal of Brain and Nervous Diseases

基　　金：上海重点研发计划申报书(AB2021006)。

摘　　要：目的探讨雷帕霉素(RAP)对蛛网膜下腔出血(SAH)大鼠脑损伤的保护作用。方法制作雄性SD大鼠SAH模型,根据处理方法不同将大鼠分为假手术组(sham组)、SAH组、RAP组和三甲基腺嘌呤(3-MA)组,每组各20只。采用Morris水迷宫评估大鼠潜伏期时间及穿越原平台次数,采用免疫组化法检测Beclin-1和LC3-Ⅱ的表达水平,采用TUNEL法评价大脑皮质细胞凋亡的严重程度,采用透射电镜观察细胞器超微结构,分析比较组间差异。结果4组间大鼠潜伏期时间、穿越原平台次数、Beclin-1和LC3-Ⅱ表达水平、神经细胞凋亡指数均有明显差异(P<0.05),潜伏期时间由短到长、穿越原平台次数由多到少、神经细胞凋亡指数由低到高均依次为sham组、RAP组、SAH组和3-MA组,Beclin-1和LC3-Ⅱ表达水平由低到高依次为sham组、3-MA组、SAH组和RAP组,组间两两比较差异均有统计学意义(P<0.05)。结论RAP可增强自噬活性,抑制细胞凋亡,改善学习记忆功能,为临床治疗早期脑损伤(EBI)提供了一个新的思路和方法。Objective To explore the protective effect of rapamycin on brain injury in rats with subarachnoid hemorrhage(SAH).Methods Male SD rat SAH models were made and divided into sham operation group(sham group),SAH group,RAP group and 3-methyladenine(3-MA)group according to different processing methods,with 20 rats in each group.Morris water maze was used to assess latency time and number of crossing the original platform in rats,immunohistochemistry was used to detect the expression levels of Beclin-1 and LC3-Ⅱ,TUNEL assay was used to evaluate the severity of apoptosis in the cerebral cortex,transmission electron microscopy was used to observe organelle ultrastructure,and differences between groups were analyzed and compared.Results There were significant differences in latency time,number of crossing the original platform,Beclin-1 and LC3-Ⅱexpression levels,and neuronal apoptosis index among the four groups(P<0.05),latency time from short to long,number of crossing the original platform from many to few,and neuronal apoptosis index from low to high were sham,RAP,SAH,and 3-MA groups,and Beclin-1 and LC3-Ⅱexpression levels from low to high were sham,3-MA,SAH,and RAP groups,and pairwise comparisons between groups were statistically significant(P<0.05).Conclusion RAP can enhance autophagic activity and inhibit apoptosis,improving learning and memory function,providing a new idea and method for clinical treatment of early brain injury(EBI).

关 键 词：雷帕霉素 蛛网膜下腔出血 早期脑损伤 自噬 细胞凋亡 

分 类 号：R743.34[医药卫生—神经病学与精神病学]