Sini powder (四逆散) decoction alleviates mood disorder of insomnia by regulating cation-chloride cotransporters in hippocampus

Objective To investigate the mechanism of Sini Powder (四逆散) decoction (SND) in the treatment of insomnia. Methods The rats were randomly divided into four groups: control, model, SND-treated, and Estazolamtreated groups ( n =15 in each group). Sleep deprivation (SD) rat model was established using the modifified multiple platform method for 14 h per day for 14 days, and the behavior of the rats were observed. Na-K-Cl-cotransporter (NKCC1) and K + /Cl - cotransporter (KCC2) in the hippocampus were tested by immunohistochemistry, real-time polymerase chain reaction, and western blot. Results SD rats displayed anxiety-like behavior, which was alleviated by SND. The protein expressions of NKCC1 and KCC2 in the hippocampus were signifificantly decreased in SD rats compared with those in control rats ( P <0.05); these proteins were signifificantly increased by SND ( P <0.05). The mRNA expression of KCC2 was signifificantly decreased in SD rats (0.62±0.35 vs . 2.29±0.56; P =0.044), while SND showed a tendency to increase the mRNA of KCC2 in SD rats ( P >0.05). By contrast, the mRNA expression of NKCC1 was signifificantly increased in the hippocampus of SD rats (6.58±1.54 vs . 2.82±0.32; P =0.011), while SND decreased the mRNA expression of NKCC1 (6.58±1.54 vs. 2.79±0.81; P =0.016). Conclusions Chinese medicine SND could alleviate mood disorder of SD rats by regulating cation-chloride cotransporters, such as NKCC1 and KCC2. These fifindings would have major implications in the mechanism of SND to relieve insomnia.