RESUMEN
OBJECTIVE: To investigate the influence of melatonin on behavioral and neurological function of rats with focal cerebral ischemia-reperfusion injury via the JNK/FoxO3a/Bim pathway. METHODS: One hundred and twenty healthy male SD rats were randomized into the model group (Model: the middle cerebral artery occlusion (MCAO) model was constructed and received an equal volume of normal saline containing 5% DMSO), sham operation group (Sham: received no treatment except normal feeding), and low, medium, and high dose of melatonin group (L-MT, M-MT, and H-MT intraperitoneally injected 10, 20, and 40 mg/kg melatonin 30 min after IR, respectively), with 24 rats in each group. Following 24 h of reperfusion, the rats in each of the above groups were tested for neurological deficit symptoms and behavioral changes to screen the rats included in the study. HE and TUNEL stainings were performed to observe pathological changes. Levels of oxidative stress-related indexes, inflammatory factor-related indexes, nuclear factor-κB p65 (NF-κB p65), and interferon-γ (IFN-γ) in the rat brain were measured by ELISA. The JNK/FoxO3a/Bim pathway-related proteins as well as Bcl-2, Caspase-3, and Bax were examined using Western blot. RESULTS: Detection of behavioral indicators showed that the MACO model was successfully constructed in rats. L-MT, M-MT, and L-MT groups presented reduced malondialdehyde (MDA), reactive oxygen species (ROS), tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, IL-1ß, IFN-γ, NF-κB p65, and apoptosis compared with the Model group (P < 0.05), and the improvement degree was better in the M-MT group versus the L-HT group. Bcl-2 protein expression in the brain tissue of L-MT, M-MT, and H-MT groups increased significantly, while Bax, Caspase-3, p-JNK, p-FoxO3a, and Bim protein expression declined markedly, versus the Model group (P < 0.05). The changes of indexes were greater in the M-MT group compared with that in the L-MT group. No significant difference was observed in all the above indexes between the M-MT group and the H-MT group (P > 0.05). CONCLUSIONS: In the MACO rat model, melatonin can effectively reduce Bax and Caspase-3 levels by modulating the JNK/FoxO3a/Bim pathway, inhibit neuronal apoptosis, and alleviate neurological deficits by reducing the release of proinflammatory mediators, with anti-inflammatory and antioxidant effects. In addition, 20 mg/kg is the optimal melatonin concentration.
Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Melatonina/farmacología , Daño por Reperfusión/tratamiento farmacológico , Animales , Proteína 11 Similar a Bcl2/metabolismo , Conducta Animal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/patología , Encéfalo/fisiopatología , Isquemia Encefálica/fisiopatología , Isquemia Encefálica/psicología , Biología Computacional , Modelos Animales de Enfermedad , Proteína Forkhead Box O3 , Mediadores de Inflamación/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Melatonina/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/fisiopatología , Daño por Reperfusión/psicologíaRESUMEN
BACKGROUND: Constipation is a common clinical problem with insufficient attention. Medication-emergent constipation is a rarely studied adverse reaction in patients with obsessive-compulsive disorder (OCD). METHODS: In this descriptive study, we retrospectively investigated the prevalence of laxative use and its relationship with clinical characteristics in hospitalized OCD patients. A total of 51 OCD patients were included in the final analysis. RESULTS: The proportion of patients using laxatives was 31.4%, and the commonly used laxatives were phenolphthalein tablet, lactulose and congrongtongbian oral liquid (a patent herbal medicine). In the laxative group, hospital stays were longer when compared to the nonlaxative group. Moreover, the dose of paroxetine was higher in patients treated with laxatives than in those without laxative use. Correlation analysis indicated that laxative use was positively associated with hospital stays, as well as the dose of paroxetine. CONCLUSION: The current study provided a preliminary picture of constipation and laxative use in hospitalized OCD patients. Close monitoring and treatment of constipation are recommended in OCD patients with pharmacotherapy.