Therapeutic effects of Jiaotai pill on rat insomnia via regulation of GABA signal pathway

摘要

Purpose: To investigate the therapeutic effects of Jiaotai pill (JTP) on rats with insomnia induced by p-chlorophenylalanine (PCPA). Methods: Rats with PCPA-induced insomnia were divided into 5 groups (n = 10), made up of control group, positive treatment group (estazolam 0.1 mg/kg), and 3 JTP treatment groups (0.6, 1.2 and 2.4 g/kg). Another group of 10 rats were treated as normal group. Rats in normal and control groups were treated with normal saline (10 mL/kg). After 14 days of drug treatment, the rats were injected intraperitoneally with sodium pentobarbital (45 mg/kg) and thereafter, latent period and sleeping time were recorded, while contents of γ-aminobutyric acid (GABA) and glutamic acid (Glu) in hypothalamus were determined by high performance liquid chromatography (HPLC). Furthermore, the ex pressions of glutamate decarboxylase 65 (GAD-65), glutamate decarboxylase 67 (GAD-67), GABA-aminotransferase (GABA)-T, anti-GABA transporter 1 (GAT)-1, anti-GABA transporter (GAT)-3, and GABA receptors (GABA-A and GABA-B) in the hypothalamus were analyzed by western blotting assay. Results: The results showed that JTP (0.6, 1.2 and 2.4 g/kg) significantly shortened latent period and prolonged sleeping time (p 0.01). JTP also increased GABA level (p 0.01), but decreased Glu contents of the rat hypothalamus (p 0.01). Western blotting data indicate that JTP significantly up-regulated the levels of GAD-65 (p 0.01), GAD-67 (p 0.05), GAT-1 (p 0.01), GAT-3 (p 0.01), GABA-A (p 0.01) and GABA-B (p 0.01), while the level of GABA-T was down-regulated. Conclusion: The results demonstrate that JTP possesses significant sedative effects on insomnia in rats, most probably through a mechanism involving GABA signal pathway.