白藜芦醇对缺氧缺血性脑损伤模型新生大鼠认知功能及SIRT1/NF-κB信号通路的影响
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篇名: 白藜芦醇对缺氧缺血性脑损伤模型新生大鼠认知功能及SIRT1/NF-κB信号通路的影响
TITLE:
摘要: 目的:研究白藜芦醇对缺氧缺血性脑损伤模型新生大鼠认知功能及沉默信息调节因子1(SIRT1)/核转录因子κB(NF-      κB)信号通路的影响。方法:将SD新生大鼠随机分为假手术组(生理盐水)、模型组(生理盐水)和白藜芦醇低、高剂量组(30、60 mg/kg),每组12只,假手术组大鼠行假手术,其余各组大鼠采用Rice法建立缺氧缺血性脑损伤模型,建模成功后,各组大鼠每天腹腔注射相应药物,连续给药6周。采用水迷宫实验分析各组大鼠空间学习记忆功能,记录给药1、3、6周后的逃避潜伏期和给药6周后的穿台次数。采用2,3,5-氯化三苯基四氮唑(TTC)染色法观察各组大鼠给药6周后的脑组织梗死面积,Western blot方法检测海马组织CA1区内凋亡相关蛋白B淋巴细胞瘤2(Bcl-2)及其相关X蛋白(Bax)、胱天蛋白酶3(Caspase-3)表达和SIRT1/NF-κB通路相关蛋白SIRT1、磷酸化NF-κB(p-NF-κB)表达。结果:与假手术组比较,模型组大鼠给药1、3、6周后的逃避潜伏期明显延长(P<0.05),给药6周后的穿台次数明显减少(P<0.05),脑组织梗死面积明显增加(P<0.05),海马组织CA1区内Bax、Caspase-3、p-NF-κB蛋白表达明显增强,Bcl-2、SIRT1蛋白表达明显降低(P<0.05)。与模型组比较,白藜芦醇低、高剂量组大鼠给药1、3、6周后的逃避潜伏期明显缩短(P<0.05),给药6周后的穿台次数明显增加(P<0.05),脑组织梗死面积明显减小(P<0.05),海马组织CA1区内Bax、Caspase-3、p-NF-κB蛋白表达明显降低,Bcl-2、SIRT1蛋白表达明显增强(P<0.05),且高剂量组大鼠上述指标的改善效果明显优于低剂量组(P<0.05)。结论:白藜芦醇可改善缺氧缺血性脑损伤模型新生大鼠认知功能障碍,其可能与SIRT1/NF-κB信号通路有关。
ABSTRACT: OBJECTIVE: To study the effects of resveratrol (Res) on cognitive function and SIRT1/NF-κB signaling pathway in neonatal rats with hypoxic-ischemic brain injury. METHODS: SD neonatal rats were randomly divided into sham operation group (normal saline), model group (normal saline), Res low-dose and high-dose groups (30, 60 mg/kg), with 12 rats in each group. Except that sham operation group received sham operation, hypoxic-ischemic brain injury model was established by Rice method in other groups. After modeling, the rats were given relevant medicine intraperitoneally each day, for consecutive 6 weeks. Water maze test was used to analyze spatial learning and memory function of rats in each group. The escape latency after 1, 3 and 6 weeks of administration and the times of crossing platform after 6 weeks of administration were recorded. TTC staining was used to detect cerebral infraction area of rats after 6 weeks of medication. Western blot was used to detect the expression of Bcl-2, Bax, Caspase-3, SIRT1, SIRT1/NF-κB pathway related protein SIRT1 and p-NF-κB in hippocampal CA1 region. RESULTS: Compared with sham operation group, escape latency of rats was prolonged significantly in model group after 1, 3, 6 weeks of medication (P<0.05), the times of crossing platform was decreased significantly after 6 weeks of medication (P<0.05); the area of cerebral infarction was increased significantly (P<0.05); the protein expression of Bax, Caspase-3 and p-NF-κB in hippocampus CA1 region were increased significantly, while the protein expression of Bcl-2 and SIRT1 were decreased significantly (P<0.05). Compared with model group, the escape latency of Res low-dose and high-dose groups were shortened significantly after 1, 3, 6 weeks of medication (P<0.05), while the times of crossing platform was increased significantly after 6 weeks of medication (P<0.05); the area of cerebral infarction was decreased significantly (P<0.05), and the protein expression of Bax, Caspase-3 and p-NF-κB protein in hippocampal CA1 area were decreased significantly, while the protein expression of Bcl-2 and SIRT1 were increased significantly (P<0.05). The improvement of above indexes in high-dose group were significantly better than low-dose group (P<0.05). CONCLUSIONS: Res can improve cognitive dysfunction in neonatal rats with hypoxic-ischemic brain injury, which is related with SIRT1/NF-κB signaling pathway.
期刊: 2019年第30卷第9期
作者: 陈灵,张相林,柳芳,周汉明
AUTHORS: CHEN Ling,ZHANG Xianglin,LIU Fang,ZHOU Hanming
关键字: 缺氧缺血性脑损伤;白藜芦醇;沉默信息调节因子1;核转录因子κB;认知功能;新生大鼠
KEYWORDS: Hypoxic-ischemic brain injury; Resveratrol; SIRT1; NF-κB; Cognitive function; Neonatal rat
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