It has been reported that antioxidative enzymes, neuropeptide Y (NPY), and c-AMP response element-binding protein (CREB) are involved in regulating phenylpropanolamine (PPA)-mediated appetite suppression. Here, we investigated whether Y1 receptor (Y1R) might be involved in this regulation. Rats were daily treated with PPA for 4 days. Changes in the contents of NPY, Y1R, glutathione peroxidase (GP), and CREB were assessed and compared. Results showed that Y1R, GP, and CREB increased, with a maximal increase about 100, 200, and 150 %, respectively, on Day 2. By contrast, NPY decreased with a biggest reduction about 48 % on Day 2 and the pattern of expression during PPA treatment was opposite to those of Y1R, GP, and CREB. Central knockdown (using antisense) or inhibition (using antagonist) of Y1R expression modulated the anorectic response of PPA and the reciprocal regulation between NPY and GP (or CREB), revealing an essential role of Y1R in regulating NPY, GP, and CREB. These results suggest that Y1R participates in the reciprocal regulation of NPY, GP, and CREB in the hypothalamus during PPA treatment in conscious rats. The present results may aid the therapeutic research of PPA and related antiobesity drugs. 相似文献
High mobility group box 1 (HMGB1) released from sensory nerve tissues can induce neuropathic pain. Whether HMGB1 is implicated in the mechanism underlying the effect of lidocaine in pain management remains to be determined. This study aims to explore the effect of lidocaine in a rat model of spared nerve injury (SNI) and the underlying mechanism. An SNI model was established via nerve ligation. Two weeks after the SNI model was established, rats were intrathecally injected with lidocaine, an HMGB1 antibody (HMG Ab), an MIP-1α antibody (MIP-1α Ab), a CCR1 inhibitor (CCR1-RS) or a CCR5 antagonist (CCR5-Mar). Pain behaviors were assessed before and after model establishment to calculate the number of spontaneous flinches (NSF), paw withdrawal threshold (PWT), paw withdrawal thermal latency (PWL) and sciatic function index (SFI). Cell apoptosis and the inflammatory response in the cerebrospinal fluid (CSF) were detected by TUNEL staining and ELISA. The mRNA and protein expression levels of MIP-1α, CCR1 and CCR5 were determined by RT-PCR and Western blotting. The expression levels of HMGB1, MIP-1α, CCR1 and CCR5 were measured by Western blotting and immunofluorescence. Pain behavior testing in SNI rats showed that SNI rats exhibited an increased NSF and a decreased PWT, PWL and SFI. Cell apoptosis in the spinal dorsal horn and the generation of inflammatory cytokines were enhanced in SNI rats, and the expression levels of HMGB1, MIP-1α, CCR1 and CCR5 were upregulated. HMGB1 cytoplasmic translocation, the coexpression of MIP-1α with NeuN, and the coexpression of CCR1 and CCR5 with OX42 were also observed in SNI rats. Neuropathic pain and neuroinflammation were suppressed by the intrathecal injection of lidocaine, HMG Ab, MIP-1α Ab, CCR1-RS or CCR5-Mar. Lidocaine inhibited the expression levels of HMGB1, MIP-1α, CCR1 and CCR5, and the HMGB1 antibody suppressed the expression of MIP-1α, CCR1 and CCR5. Lidocaine attenuates neuropathic pain and neuroinflammation by inhibiting HMGB1 to regulate the MIP-1α/CCR1/CCR5 pathway.
Serotonin modulates diverse brain functions. Beyond its clinical antidepressant effects, it improves motor performance, learning and memory formation. These effects might at least be partially caused by the impact of serotonin on neuroplasticity, which is thought to be an important foundation of the respective functions. In principal accordance, selective serotonin reuptake inhibitors enhance long-term potentiation-like plasticity induced by transcranial direct current stimulation (tDCS) in humans. As other neuromodulators have discernable effects on different kinds of plasticity in humans, here we were interested to explore the impact of serotonin on paired associative stimulation (PAS)-induced plasticity, which induces a more focal kind of plasticity, as compared with tDCS, shares some features with spike timing-dependent plasticity, and is thought to be relative closely related to learning processes. In this single-blinded, placebo-controlled, randomized crossover study, we administered a single dose of 20 mg citalopram or placebo medication and applied facilitatory- and excitability-diminishing PAS to the left motor cortex of 14 healthy subjects. Cortico-spinal excitability was explored via single-pulse transcranial magnetic stimulation-elicited MEP amplitudes up to the next evening after plasticity induction. After citalopram administration, inhibitory PAS-induced after-effects were abolished and excitatory PAS-induced after-effects were enhanced trendwise, as compared with the respective placebo conditions. These results show that serotonin modulates PAS-induced neuroplasticity by shifting it into the direction of facilitation, which might help to explain mechanism of positive therapeutic effects of serotonin in learning and medical conditions characterized by enhanced inhibitory or reduced facilitatory plasticity, including depression and stroke. 相似文献
In crossover studies rabbits were given sulfmpyrazone (SO) and its sulfide metabolite (S) perorally once daily (10 mg/kg) for 5 days. Comparison of the pharmacokinetic parameters obtained after the first and the fifth dose indicates that repeated dosing does not alter disposition kinetics of both SO and S, except that in dosing with S the observed terminal half-life for S is significantly reduced, from 4.59 ± 0.55 to 2.86 ± 0.6 hr (SD). In other studies rabbits were given higher single doses (15, 25, and 50 mg/kg) perorally and comparison was made between these dose sizes and the first dose (10 mg/kg) of multiple administration with S. Some kinetic parameters tended to be altered in a nonlinear fashion, and greater intersubject variations were observed because of the dose increase, while oxidation to SO or p-hydroxylation to OH-S from S was not significantly altered. 相似文献
In the present study, we tested ethanolic extracts from 10 Chinese herbs for their effects on K562, Raji, Wish, HeLa, Calu-1, and Vero tumor cells proliferation. On a percentage basis, panaxynol purified from Saposhnikovae divaricata had the highest inhibitory activity on various tumor cells proliferation. Cell-cycle analysis indicated that panaxynol arrested the cell cycle progression of tumor cells from the G1 transition to the S phase. In an attempt to further localize the point in the cell cycle where arrest occurred, gene expression of cyclin E, a key regulatory event leading to the G1/S boundary was examined. Results indicated that the levels of cyclin E mRNA in various tumor cells were decreased by panaxynol. Thus, the suppressant effects of panaxynol on proliferation of various tumor cells appeared to be mediated, at least in part, through impairments of cyclin E mRNA levels and arresting cell cycle progression in the cells. 相似文献
Although annual influenza vaccinations are recommended by many authorities, some doctors may be reluctant to vaccinate asthmatic children because of the risk of inducing bronchial reactivity and exacerbating the asthma. In this study, the effect of split influenza vaccine on clinical symptoms, airway responsiveness and its influence on T lymphocytes was evaluated. Twenty-one asthmatic children with stable asthma were recruited and divided into two groups. Eleven patients who received the influenza vaccine formed the vaccination group and 10 patients who received a placebo formed the placebo group. Forced expiratory volume in 1 s ( FEV 1), airway response (PC20 methacholine, PC20 = provocation concentration causing a 20% fall in FEV 1) and the T lymphocyte subset ratio (Th1/Th2) were recorded on day 1 pre-vaccination and day 14 post-vaccination. Patients were also asked to record their peak expiratory flow (PEF) every morning and evening and to complete daily symptom scores over the period of 2 weeks. There were no significant changes in PC20, FEV 1, PEF variability, symptom scores and the Th1/Th2 ratio between the vaccination and placebo groups between day 1 pre-vaccination and day 14 post-vaccination. Similar results of PEF variability and asthma symptom score were obtained when the analysis was restricted to the day 1 pre-vaccination and day 3 post-vaccination. Immunization with split influenza vaccine does not exacerbate asthma in children either with a clinical or immunological effect. These results suggest that children with stable asthma can safely be immunized with a split influenza vaccine. 相似文献