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【Objective】 To investigate the central sedative and hypnotic effects and mechanisms of Shumian Capsule. 【Methods】 The blank control group, the positive drug diazepam group, and the low-, medium-, and high-dose groups of Shumian Capsule were designed in the experiments. Male Kunming mice were administered orally by gavage. We conducted the experiment of mouse autonomous activity, and assessed supra- and sub-threshold dose sleep with pentobarbital sodium, respectively. The levels of γ-aminobutyric acid (GABA) and glutamic acid (Glu) in the brain tissue of the mice were measured by enzyme-linked immunosorbent assay (ELISA) or colorimetric method. Male SD rats were injected intraperitoneally with p-chlorophenyl alanine [PCPA, 350 mg/(kg·d)] to establish an insomnia rat model, after which rats were continuously administered intragastrically for 7 days. The general status and body weight of the rats were observed. Total distance and standing times of rats were measured by open field test. Western blotting and immunohistochemistry assays were used to evaluate the protein expression of 5-HT1A receptor (5-HT1AR) in the rat hippocampus. 【Results】 Compared with the blank control group, the three dose groups of Shumian Capsule [1.6, 3.2, 6.4 mg/(kg·d)] for 14 consecutive days had significantly reduced the number of spontaneous activities and standing times in the mice (P<0.01). The high dose significantly prolonged the sleep duration of the mice induced by the supra-threshold dose of pentobarbital sodium (P<0.01). Compared with the blank control group, each dose group of Shumian Capsule had an increased GABA level in the mouse brain tissue in a dose-dependent manner (P<0.05); the medium- and high-dose groups had significantly reduced Glu levels in the hippocampus (P<0.05), while the high-dose group had significantly reduced Glu level in the cortex (P<0.05). In insomnia model rats, their activity was sluggish; their circadian activity rhythm disappeared; the hair became hard, rough and dull, with severe hair loss; and their weight reduced. After 7 consecutive days of the drug administration, the rats’ mental state in each Shumian Capsule dose group was improved. Compared with the blank control group, the rats’ body weight gains were significantly reduced after intraperitoneal injection of PCPA (P<0.01). Compared with the model group, each rat group of Shumian capsule treatment had significantly increased body weight gains (P<0.01). Compared with the blank control group, the distance of the rats in the model group increased in the open field test, and the expression level of 5-HT1AR protein in the hippocampus decreased. However, the distance of rats in diazepam group and each dose group of Shumian Capsule was significantly reduced (P<0.01), and the expression level of 5-HT1AR protein in the hippocampus of the high- and medium-dose groups of Shumian Capsule and diazepam group increased significantly (P<0.01). 【Conclusion】 Shumian Capsule has obvious effects of sedation, hypnosis and insomnia improvement, and its underlying mechanisms may be related to the increased GABA and decreased Glu contents in brain tissues, as well as up-regulated 5-HT1AR protein expression in the hippocampus.
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<p><b>OBJECTIVE</b>To observe the effects of acupuncture on mRNA of the neurotransmitter serotonin transporter (5-HTT), 5-HTreceptor (5-HTR), norepinephrineα2 receptor (NEαR) in brain tissue in rats with post-stroke depression.</p><p><b>METHODS</b>Forty male SD rats were randomly divided into a normal group, a model group, a medication group and an acupuncture group, 10 rats in each one. The model of post-stroke depression was established by occlusion of middle cerebral artery and chronic unpredictable mild stress method. After model was successfully established, the rats in the normal group and model group received no treatment; the rats in medication group were treated with intragastric administration of fluoxetine (2 mg/kg); the rats in acupuncture group were treated with acupuncture at "Baihui" (GV 20), "Fengfu" (GV 16), "Shenmen" (HT 7) and "Taichong" (LR 3) for 20 min, during which manual stimulation was given once, once a day, 7 days as one course, and totally 3 courses were given with an interval of one day between courses. The changes of rat behavior and 5-HT, NE were observed after intervention; the RT-PCR method was applied to observe the mRNA of 5-HTT, 5-HTR, NEαR in hippocampus, raphe nucleus and locus coeruleus.</p><p><b>RESULTS</b>After treatment, compared with the normal group, the Zea Longa score in the model group was increased, while sugar water consumption, the number of horizontal and vertical movement of open-field test was reduced (all<0.01); compared with the model group, the Zea Longa score in the medication group and acupuncture group was reduced, while sugar water consumption, the number of horizontal and vertical movement of open-field test were increased (<0.01,<0.05); compared between the medication group and acupuncture group, the behavior changes were not significantly different (all>0.05). After treatment, compared with the normal group, the content of 5-HT and NE in brain tissue and mRNA expression of 5-HTT, 5-HTR in hippocampus, raphe nucleus and locus coeruleus in the model group were reduced (all<0.01), but the mRNA expression of NEαR was increased (<0.01);compared with the model group, the content of 5-HT and NE in brain tissue and mRNA expression of 5-HTT, 5-HTR in hippocampus, raphe nucleus and locus coeruleus in the medication group and acupuncture group were increased (<0.01,<0.05), while the mRNA expression of NEαR was reduced (all<0.01). The differences between medication group and acupuncture group were not significantly different (all>0.05).</p><p><b>CONCLUSIONS</b>Acupuncture could significantly improve behavioral change in rats with post-stroke depression, which may be related to the regulation of 5-HT, NE in cerebral cortex as well as mRNA expressions of 5-HTT, 5-HTR, NEαR in hippocampus, raphe nucleus and locus coeruleus.</p>
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Aim To explore the effect of meloxicam on the CUMS-induced depressive-like behaviors in rats and its preliminary mechanism. Methods The rats were exposed to CUMS procedure for 6 weeks to estab-lish the model of depression. Meloxicam(1,3 mg· kg-1 ) and sertraline(5 mg·kg-1 ) were administered to rats from 22d of the stress procedure(once a day,for 21 days,p. o. ) . Depressive-like behaviors were evalu-ated by the open-field test and force swimming test. The levels of PGE2 and TNF-αin cortex were measured by ELISA. Moreover, the concentrations of NE, DA, DOPAC and 5-HIAA were also measured by HPLC, and the protein expression of 5-HT1 AR in cortex was analyzed by the immunohistochemistry. Results Com-pared with the rats of normal control group,the vertical and horizontal movement scores of rats in the open-field test were decreased and the immobility time in the forced swimming test was increased in model group. The levels of PGE2 and TNF-α were both increased signifi-cantly,whereas the concentrations of NE, DA, DOPAC and 5-HIAA were decreased and the expression of 5-HT1AR was reduced in cortex. Compared with the rats of model group, meloxicam significantly improved the depressive behaviors of rats in experimental groups and reversed the content of PGE2 ,TNF-α,NE,DA,DOPAC and 5-HIAA, as well as the expression of 5-HT1AR. Conclusion Meloxicam has a significant protective effect on CUMS-induced depressive-like behaviors, and the protective mechanism might be related to atten-uating inflammation response and reconstructing the balance of the monoamine neurotransmitter system in rat cortex.