Effect of Modified Tianwang Buxindan on Learning and Memory Function and Expression of Inflammatory Factors in Sleep Deprived Rats / 中国实验方剂学杂志

ABSTRACT

Objective:By studying the effects of Tianwang Buxindan on sleep quality， cognitive function， inflammatory factors and immune-related gene expression in sleep deprivation model rats， explore the effect of Tianwang Buxindan on the learning and memory process under sleep deprivation and its anti-inflammatory effects possible mechanism. Method:The 40 male SPF rats were used to simulate the sleep deprivation model by multi-platform water environment method， and were randomly divided into model group， Tianwang Buxindan group （20 g·kg-1） and estazolam group （0.1 mg·kg-1）， set up a normal group， 10 in each group. A total of 4 weeks of sleep deprivation modeling was performed， and drug intervention was performed 2 weeks later. The model group and the blank group were given equal volumes of pure water. Electroencephalogram （EEG） evaluation of modeling and analysis of sleep structure and quality of rats， Morris water maze positioning navigation and space exploration experiment analysis of learning and memory ability of rats， application of enzyme-linked immunosorbent assay （ELISA） was used to detect the serum inflammatory factor interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， monocyte chemokine-1 （MCP-1） expression， Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA levels of EB virus inducible gene 3 （EBI3）， extracellular signal-regulated kinase 5 （ERK5）， and p21 activated protein kinase 4 （PAK4）. Result:The sleep deprivation model was successfully built. Compared with blank group， the total sleep time， total duration of slow wave sleep and the duration of the first and second phases of slow wave sleep in the model group were significantly shortened （P<0.01）. The incubation period on the upper platform， the total swimming distance and the time to reach the original platform for the first time increased significantly， while the number of times to cross the platform and the target quadrant significantly decreased （P<0.05，P<0.01）. The expression levels of IL-1β，TNF-α and MCP-1 increased significantly （P<0.01）， the mRNA expression levels of EBI3， ERK5 and PAK4 in the hypothalamus of the model group decreased significantly （P<0.01）. Compared with the model group， the sleep quality of the rats in the Tianwang Buxindan group was significantly improved. The total sleep time， the total duration of slow wave sleep and the duration of the first phase of slow wave sleep were significantly increased （P<0.01）. The incubation period on the platform， the total swimming distance and the time to reach the original platform for the first time are shortened， the number of times to cross the platform and the target quadrant time are extended （P<0.05，P<0.01）， IL-1β， TNF-α， MCP-1 expression levels were significantly reduced （P<0.05，P<0.01）， mRNA expression levels of EBI3， ERK5 and PAK4 in rat hypothalamus were significantly increased （P<0.05，P<0.01）. Conclusion:Tianwang Buxindan can improve the sleep quality and learning and memory ability of sleep deprivation model rats， which may be related to the increase of the expression level of related inflammatory factors and its anti-inflammatory effect.