生慧汤对APP/PS1双转基因痴呆模型小鼠下丘脑区生物钟基因Bmal1及海马IL-6，TNF-<italic style="font-style: italic">α</italic>的影响

张美娅; 王平; 游秋云; 丁莉

doi:10.13422/j.cnki.syfjx.20192001

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生慧汤对APP/PS1双转基因痴呆模型小鼠下丘脑区生物钟基因Bmal1及海马IL-6，TNF-α的影响

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- 生慧汤对APP/PS1双转基因痴呆模型小鼠下丘脑区生物钟基因Bmal1及海马IL-6，TNF-α的影响
- Effect of Shenghuitang on Bmal1 in Hypothalamus and IL-6 and TNF-α in Hippocampus of APP/PS1 Double Transgenic Dementia Model Mice
- 中国实验方剂学杂志 2019年25卷第20期页码：7-12
- 作者机构：
  
  湖北中医药大学，武汉　 430065
- 作者简介：
  
  张美娅，硕士，从事中药药理学和毒理学研究，E-mail：545357895@qq.com
  丁莉，博士，副教授，从事老年病防治及失眠药物研究，E-mail：17767153@qq.com
- 基金信息：
  
  国家自然科学基金项目(81703972)
- DOI：10.13422/j.cnki.syfjx.20192001
  中图分类号： R2-0; R22; R285.5; R289
- 收稿日期：2019-03-01，
  
  网络出版日期：2019-07-02，
  
  纸质出版日期：2019-10-20
- 稿件说明：
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张美娅, 王平, 游秋云, 等. 生慧汤对APP/PS1双转基因痴呆模型小鼠下丘脑区生物钟基因Bmal1及海马IL-6，TNF-α的影响[J]. 中国实验方剂学杂志, 2019,25(20):7-12.

Mei-ya ZHANG, Ping WANG, Qiu-yun YOU, et al. Effect of Shenghuitang on Bmal1 in Hypothalamus and IL-6 and TNF-α in Hippocampus of APP/PS1 Double Transgenic Dementia Model Mice[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(20): 7-12.
张美娅, 王平, 游秋云, 等. 生慧汤对APP/PS1双转基因痴呆模型小鼠下丘脑区生物钟基因Bmal1及海马IL-6，TNF-α的影响[J]. 中国实验方剂学杂志, 2019,25(20):7-12. DOI： 10.13422/j.cnki.syfjx.20192001.

Mei-ya ZHANG, Ping WANG, Qiu-yun YOU, et al. Effect of Shenghuitang on Bmal1 in Hypothalamus and IL-6 and TNF-α in Hippocampus of APP/PS1 Double Transgenic Dementia Model Mice[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(20): 7-12. DOI： 10.13422/j.cnki.syfjx.20192001.

摘要

目的：

通过观察生慧汤对APP/PS1双转基因痴呆模型小鼠学习记忆、下丘脑区生物钟基因Bmal1及海马白细胞介素-6(IL-6)，肿瘤坏死因子-

(TNF-

)的影响，探索生慧汤改善学习记忆和睡眠障碍的可能机制。

方法：

将实验小鼠随机分为模型组、正常组、褪黑素组、生慧汤高剂量组和生慧汤低剂量组。采用自主活动分析系统检测各组小鼠自主活动；采用Morris水迷宫检测各组小鼠学习能力及空间记忆能力；采用实时荧光定量聚合酶链式反应(Real-time PCR)检测各组小鼠下丘脑区钟基因Bmal1 mRNA表达，蛋白免疫印迹法(Western blot)检测各组小鼠Bmal1蛋白表达；采用酶联免疫吸附测定(ELISA)检测小鼠海马区IL-6，TNF-

含量；采用皮尔森(Pearson)分析方法分析IL-6，TNF-

与Bmal1的相关性。

结果：

自主活动结果显示，与正常组比较，模型组小鼠活动次数和活动路程显著减少(

0.01)；与模型组比较，各给药组小鼠活动次数和活动路程均明显增加(

0.05，

0.01)，生慧汤低剂量组无显著性差异。Morris水迷宫结果显示，与正常组比较，模型组小鼠上平台潜伏期与游泳总路程显著延长(

0.01)，穿越平台次数与目标象限时间显著减少(

0.01)，第1次抵原平台时间明显增加(

0.05)；与模型组比较，各给药组小鼠上平台潜伏期与游泳总路程明显减少(

0.05，

0.01)，穿越平台次数与目标象限时间明显增加(

0.05，

0.01)，第1次抵原平台时间明显减少(

0.05，

0.01)。Real-time PCR结果显示，与正常组比较，模型组小鼠Bmal1 mRNA表达上调；与模型组比较，各给药组小鼠Bmal1 mRNA表达下调。Western blot结果显示，与正常组比较，模型组小鼠Bmal1蛋白表达显著升高(

0.01)；与模型组比较，褪黑素组、生慧汤高、低剂量组Bmal1蛋白表达显著降低(

0.01)。ELISA结果显示，与正常组比较，模型组小鼠IL-6，TNF-

含量显著升高(

0.01)；与模型组比较，各给药组IL-6，TNF-

含量显著降低(

0.01)。Pearson分析结果显示，IL-6，TNF-

与Bmal1具有相关性，且呈负相关关系。

结论：

生慧汤可能通过上调下丘脑区Bmal1基因的表达来降低海马区炎症因子IL-6，TNF-

蛋白含量，从而改善阿尔兹海默症(AD)和昼夜节律紊乱。

Abstract

Objective:

To investigate the effect of Shenghuitang on learning and memory

biological clock gene [brain and muscle arnt-like 1 (Bmal1)] in hypothalamus and interleukin-6(IL-6)and tumor necrosis factor-

(TNF-

)in hippocampus of APP/PS1 double transgenic dementia model mice

in order to explore the possible mechanism of Shenghuitang to improve learning and memory and sleep disorders.

Method:

The experimental mice were randomly divided into model group

blank control group

melatonin group

high-dose Shenghuitang group and low-dose Shenghuitang group. Autonomic activity analysis system was used to detect the autonomic activities of mice in each group. Morris water maze was used to detect the learning ability and spatial memory ability of each group. quantitative real-time fluorescence polymerase chain reaction(Real-time PCR) was used to detect the expression of Bmal1 mRNA in the hypothalamic area of mice. Western blot was used to detect the expression of Bmal1 protein in each group. The content of inflammatory factors IL-6 and TNF-

in hippocampus of mice was detected by enzyme-linked immunosorbent assay(ELISA). The correlation between inflammatory factors IL-6

TNF-

and Bmal1 gene was analyzed by pearson analysis.

Result:

The results of voluntary activities showed that compared with the control group

the number of activities and activity distance of the model group were significantly decreased (

0.01). Compared with the model group

the number of activities and activity distance of the mice in each drug group increased significantly (

0.05

0.01)

there was no significant difference in the low dose group of Shenghuitang. Morris water maze results showed that compared with the control group

the platform latency and swimming total distance were significantly prolonged in the model group (

0.01)

and the number of crossing platforms and target quadrant time was significantly reduced (

0.01). The original platform time increased significantly (

0.05). Compared with the model group

the platform latency and total swimming distance were significantly decreased in each group (

0.05

0.01)

and the number of crossing platforms and target quadrant time increased significantly(

0.05

0.01)

the time to the original platform was significantly reduced (

0.05

0.01). Real-time PCR results showed that the expression of Bmal1 mRNA was up-regulated in the model group compared with the control group. Compared with the model group

the mRNA expression of Bmal1 gene was down-regulated in each group. Western blot results showed that compared with the control group

the expression of Bmal1 protein in the model group was significantly increased (

0.01). Compared with the model group

Bmal1 protein expression was significantly decreased in each group(

0.01). The results of ELISA showed that the levels of IL-6 and TNF-

in the model group were significantly higher than those in the control group (

0.01). Compared with the model group

the levels of IL-6 and TNF-

in the drug group were significantly lower(

0.01). Pearson analysis showed that IL-6

TNF-

and Bmal1 were correlated and negatively correlated.

Conclusion:

Shenghuitang may reduce the levels of inflammatory factors IL-6 and TNF-

in hippocampus by up-regulating the expression of Bmal1 gene in hypothalamic region

thus improving Alzheimer's disease(AD) and circadian rhythm disorders.

关键词

Keywords

references

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Effect of Shenghuitang on Bmal1 in Hypothalamus and IL-6 and TNF-α in Hippocampus of APP/PS1 Double Transgenic Dementia Model Mice

DOI：10.13422/j.cnki.syfjx.20192001

摘要

Abstract

关键词

Keywords

references