天津医药

天津医药 ›› 2019, Vol. 47 ›› Issue (10): 1040-1045.doi: 10.11958/20190667

• 实验研究 • 上一篇    下一篇

鬼针草总黄酮通过ERK1/2/NF-κB通路减轻局灶性脑缺血大鼠认知功能障碍

李丽丽，焦富英   

  1. 辽宁中医药大学附属第二医院脑病一科（邮编110034）
  • 收稿日期:2019-03-12 修回日期:2019-08-01 出版日期:2019-10-15 发布日期:2019-11-11
  • 通讯作者: 李丽丽 E-mail:xubaojun9881@163.com
  • 基金资助:
     

Total flavones of bidens bipinnata L. alleviated cognitive impairment in rats with focal cerebral ischemia through ERK1/2/NF-κB pathway

LI Li-li, JIAO Fu-ying   

  1. Department of Encephalopathy, the Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110034, China
  • Received:2019-03-12 Revised:2019-08-01 Published:2019-10-15 Online:2019-11-11
  • Supported by:
     

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摘要： 摘要：目的 探讨鬼针草总黄酮（TFB）对局灶性脑缺血大鼠认知功能的影响及可能的作用机制。方法 72只大 鼠随机分为假手术组、模型组、阳性对照组（1 mg/kg尼莫地平）、低剂量TFB组（25 mg/kg）、中剂量TFB组（50 mg/kg）、 高剂量TFB组（100 mg/kg），每组12只。采用改良线栓法建立局灶性脑缺血大鼠模型。Morris水迷宫实验检测大鼠 学习和记忆能力，尼氏染色观察大鼠海马组织病理结构变化，酶联免疫吸附法检测海马组织脑源性神经营养因子 （BDNF）、神经生长因子（NGF）、白介素-1β（IL-1β）、白介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）含量，Western blot 检测海马组织细胞外信号调节蛋白激酶（ERK）1/2、p-ERK1/2、核转录因子（NF）-κB p65和p-NF-κB p65蛋白表达。 结果 与假手术组比，模型组大鼠逃避潜伏期延长，穿越平台次数减少，海马组织BDNF和NGF含量均降低，IL-1β、 IL-6和TNF-α含量以及p-ERK1/2和p-NF-κB p65蛋白表达水平均升高（P＜0.05）。与模型组比，第2天之后高剂量 TFB组和阳性对照组大鼠平均逃避潜伏期均降低（P＜0.05），中、高剂量TFB组和阳性对照组大鼠穿越平台次数增 加，海马组织BDNF和NGF含量升高（P＜0.05），IL-1β、IL-6和TNF-α含量以及p-ERK1/2和p-NF-κB p65蛋白表达 水平均降低，具有剂量依赖性（P＜0.05）。阳性对照组和高剂量TFB组大鼠各检测指标比较差异无统计学意义（P＞ 0.05）。结论 TFB可改善局灶性脑缺血大鼠的认知功能，其作用机制可能与抑制ERK1/2/NF-κB信号通路的传导 有关。

关键词: 脑缺血, 认知, 神经生长因子类, 脑源性神经营养因子, 细胞外信号调节MAP激酶类, NF-κB, 鬼针草总黄酮

Abstract: Abstract: Objective To investigate the effect of total flavones of bidens bipinnata L. (TFB) on cognitive function in rats with focal cerebral ischemia and its possible mechanism. Methods Seventy-two rats were randomly divided into sham operation group, model group, positive control group (1 mg/kg nimodipine), low-dose TFB group (25 mg/kg), medium-dose TFB group (50 mg/kg) and high-dose TFB group (100 mg/kg). The rat model of focal cerebral ischemia was established by modified thread embolization. Morris water maze test was used to test the learning and memory abilities of rats. The histopathological changes of hippocampus were observed by Nissl staining. The contents of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in hippocampus were detected by enzyme-linked immunosorbent assay. Western blot assay was used to detect the expressions of ERK1/2, p-ERK1/2, NF-κB p65 and p-NF-κB p65 in hippocampus. Results Compared with the sham-operated group, the average escape latency increased, the number of crossing plateau decreased, the contents of BDNF and NGF in hippocampus decreased and the contents of IL-1β, IL-6 and TNF-α, and the expressions of p-ERK1/2 and p-NF-κB p65 protein increased in the model group (P＜0.05). Compared with model group, the average escape latency of rats decreased after the second day in high dose TFB group and positive control group (P＜0.05). The number of times of rats crossing the platform increased in middle and high dose TFB groups and positive control group, and the contents of BDNF and NGF in hippocampus were also increased (P＜0.05). The contents of IL-1β, IL-6 and TNF-α and the expression levels of p-ERK1/ 2 and p-NF-kappa B p65 were all decreased in a dose-dependent manner (P＜0.05). There were no significant differences in detection indexes between positive control group and high-dose TFB group (P＞0.05). Conclusion TFB can improve cognitive function in rats with focal cerebral ischemia, and its mechanism may be related to the inhibition of ERK1/2/NF-κB signaling pathway.

Key words: brain ischemia, cognition, nerve growth factors, brain-derived neurotrophic factor, extracellular signalregulated MAP kinases, NF-kappa B, total flavones of bidens bipinnata L.

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