Effect of Shenghuitang on Bmal1 in Hypothalamus and IL-6 and TNF-α in Hippocampus of APP/PS1 Double Transgenic Dementia Model Mice
10.13422/j.cnki.syfjx.20192001
- VernacularTitle: 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
- Author:
Mei-ya ZHANG
1
;
Ping WANG
1
;
Qiu-yun YOU
1
;
Li DING
1
Author Information
1. Hubei University of Chinese Medicine, Wuhan 430065, China
- Publication Type:Research Article
- Keywords:
Shenghuitang;
Alzheimer's disease (AD);
Bmal1;
inflammatory factor
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2019;25(20):7-12
- CountryChina
- Language:Chinese
-
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-α(TNF-α)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-α in hippocampus of mice was detected by enzyme-linked immunosorbent assay(ELISA). The correlation between inflammatory factors IL-6, TNF-α 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 (P<0.01). Compared with the model group, the number of activities and activity distance of the mice in each drug group increased significantly (P<0.05, P<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 (P<0.01), and the number of crossing platforms and target quadrant time was significantly reduced (P<0.01). The original platform time increased significantly (P<0.05). Compared with the model group, the platform latency and total swimming distance were significantly decreased in each group (P<0.05, P<0.01), and the number of crossing platforms and target quadrant time increased significantly(P<0.05, P<0.01), the time to the original platform was significantly reduced (P<0.05, P<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 (P<0.01). Compared with the model group, Bmal1 protein expression was significantly decreased in each group(P<0.01). The results of ELISA showed that the levels of IL-6 and TNF-α in the model group were significantly higher than those in the control group (P<0.01). Compared with the model group, the levels of IL-6 and TNF-α in the drug group were significantly lower(P<0.01). Pearson analysis showed that IL-6, TNF-α and Bmal1 were correlated and negatively correlated. Conclusion:Shenghuitang may reduce the levels of inflammatory factors IL-6 and TNF-α in hippocampus by up-regulating the expression of Bmal1 gene in hypothalamic region, thus improving Alzheimer' s disease(AD) and circadian rhythm disorders.
