Effect of Suanzaoren Tang on Learning Memory and TLR4/NF-κB Signaling Pathway in Rats with Chronic Sleep Deprivation / 中国实验方剂学杂志

ABSTRACT

Objective:To explore the mechanism of Suanzaoren Tang in improving learning and memory impairment induced by sleep deprivation based on Toll-like receptor (TLR4)/nuclear transcription factor-κB (NF-κB) signaling pathway. Method:The experimental rats were randomly divided into blank group, model group, melatonin group (2.5×10-4 g·kg-1·d-1) and Suanzaoren Tang group (12.96 g·kg-1·d-1). Except the blank group, the chronic sleep deprivation model was established in other groups. After 28 days of continuous administration, the learning and memory of the rats were assessed by Morris water maze. The expressions of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α(TNF-α)in serum were detected by enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of TLR4, NF-κB p65 and nuclear transcription factor inhibitory protein α (IκBα) in the hippocampus of rats were detected by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), and the protein expressions of TLR4, IκBα, p-IκBα and NF-κB p65 in the hippocampus of rats were detected by immunohistochemistry (IHC). Result:Compared with the blank group, the platform latency, total swimming distance and the first landing time of the model group increased significantly (P<0.01), while the number of crossing platforms and target quadrant time decreased significantly (P<0.01). Compared with the model group, the platform latency, total swimming distance and the first platform time were reduced in the melatonin group and the Suanzaoren group (P<0.05, P<0.01), while the number of crossing platforms and target quadrants time were increased(P<0.05, P<0.01). Compared with the blank group, the expression levels of TNF-α, IL-1β and IL-6 in the model group were significantly increased (P<0.01). Compared with the model group, the levels of TNF-α, IL-1β and IL-6 in the serum of melatonin group and Suanzaoren Tang group decreased (P<0.05, P<0.01). Compared with the blank group, mRNA and protein expression levels of TLR4 and NF-κB p65 in the hippocampus of the model group were increased (P<0.01), while mRNA and protein expression levels of IκBα were decreased (P<0.01). Compared with the model group, the mRNA and protein expressions of TLR4 and NF-κB p65 in the hippocampus of melatonin group and Suanzaoren Tang group decreased (P<0.05, P<0.01), while the mRNA and protein expression levels of IκBα increased (P<0.05, P<0.01). Compared with the blank group, the protein expression level of p-IκBα in the hippocampus of the model group was significantly increased (P<0.01). Compared with the model group, the protein expression level of IκBα in the hippocampus of melatonin group and Suanzaoren Tang group was increased (P<0.05, P<0.01). Conclusion:Suanzaoren Tang can improve learning and memory impairment induced by sleep deprivation in rats, and its mechanism may be related to its inhibition of TLR4/NF-κB signaling pathway in hippocampus.