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ObjectiveTo investigate the interventional effects of Shugan Jianpi Yangxin prescription on the expression of orexin-A （OXA）， orexin-1 receptor （OX1R）， and orexin-2 receptor （OX2R） in the mouse model of insomnia. MethodThe mouse model of insomnia was established by intraperitoneal injection of DL-4-chlorophenylalanine （PCPA）. Fifty BALB/c mice were randomized into a blank group， a model group， an eszopiclone （0.13 mg·kg-1） group， and low- and high-dose （8.4 and 33.6 g·kg-1， respectively） Shugan Jianpi Yangxin prescription groups and treated with the corresponding drugs for 14 consecutive days. The weight changes of mice were monitored， and Morris water maze and pentobarbital-induced sleep tests were conducted. Immunohistochemistry （IHC） was employed to examine the expression of OXA in the hypothalamus. Enzyme-linked immunosorbent assay was used to measure the levels of OXA and 5-hydroxytryptamine （5-HT） in the hypothalamus， serum， and spleen. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of OXA， OX1R， and OX2R in the hypothalamus. ResultCompared with the blank group， the model group had decreased body weight （P<0.01）， increased escape latency （P<0.01）， increased sleep latency （P<0.01）， shortened sleep duration （P<0.01）， elevated OXA level and lowered 5-HT level in the hypothalamus， serum， and spleen （P<0.05）， and up-regulated mRNA levels of OXA， OX1R， and OX2R in the hypothalamus （P<0.01）. Compared with the model group， the low- and high-dose groups of Shugan Jianpi Yangxin prescription showed increased body weight （P<0.05， P<0.01）， shortened escape latency （P<0.05）， shortened sleep latency and prolonged sleep duration （P<0.01）， and lowered OXA level and elevated 5-HT level in the hypothalamus， serum， and spleen （P<0.05， P<0.01）. Moreover， the two doses of Shugan Jianpi Yangxin prescription down-regulated the mRNA levels of OXA， OX1R， and OX2R in the hypothalamus （P<0.01）. ConclusionShugan Jianpi Yangxin prescription exerts sedative and hypnotic effects in mice by increasing the content of 5-HT in the brain and inhibiting the expression of OXA and its receptors in the hypothalamus.
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Abstract Background Several randomized clinical trials (RCTs) have shown that dual orexin receptor antagonists (DORAs) are effective in the treatment of chronic insomnia. However, the superiority of one particular DORA over the others remains unclear. Objective To perform a network meta-analysis to evaluate the efficacy of different DORAs in patients with chronic insomnia. Methods The Medline, Embase, and Cochrane Central databases were searched for RCTs that compared DORA with placebo in patients ≥ 18 years of age with a diagnosis of insomnia disorder. We pooled outcomes for wake time after sleep onset (WASO), latency to persistent sleep (LPS), total sleep time (TST), and adverse events (AEs). Results We included 10 RCTs with 7,806 patients, 4,849 of whom received DORAs as the intervention. Overall, we found that DORAs were associated with the improvement of all analyzed efficacy outcomes. Concerning TST, an apparent dose-dependent pattern was noticed, with higherdoses relating to a longerTST. Lemborexant 10mg provided the largest reduction in WASO (at month 1) in minutes (standardized mean difference [SMD] = −25.40; 95% confidence interval [95%CI] = −40.02- −10.78), followed by suvorexant 20/15mg (SMD = −25.29; 95%CI = −36.42- −14.15), which also appeared to provide the largest decrease in long-term WASO (SMD = −23.70; 95%CI = −35.89- −11.51). The most frequent AEs were somnolence, nasopharyngitis, and headache, with rates of up to 14.8%. Conclusion Our results suggest that DORAs are associated with greater efficacy when compared with placebo in the treatment of insomnia, a complex 24-hour sleep disorder. Additionally, dosing might play an important role in the management of chronic insomnia.
Resumo Antecedentes Inúmeros ensaios clínicos randomizados (ECRs) têm demonstrado que os antagonistas duais do receptor de orexina (dual orexin receptor antagonists, DORAs, em inglês) são eficazes no tratamento da insônia. Contudo, restam dúvidas quanto à superioridade de um DORA com relação aos outros. Objetivo Realizar uma meta-análise em rede para avaliar a eficácia de diferentes DORAs em pacientes com insônia. Métodos Foram feitas buscas nas bases de dados Medline, Embase e Cochrane Central por ECRs que comparassem DORAs e placebo em pacientes ≥ 18 anos de idade com diagnóstico de insônia. Os seguintes desfechos foram selecionados: tempo desperto após o início do sono (wake time after sleep onset, WASO, em inglês), latência para o sono persistente (latency to persistent sleep, LPS, em inglês), tempo total de sono (total sleep time, TST, em inglês), e efeitos adversos (EAs). Resultados Incluímos 10 ensaios clínicos com 7,806 pacientes, 4,849 dos quais receberam DORAs como intervenção. Os DORAs foram associados à melhoria de todos os desfechos de eficácia analisados. Em relação ao TST, um aparente padrão de dependência da dose foi identificado, com doses maiores se associando a um maior TST. Lemborexant 10 mg proporcionou a maior redução em WASO (no primeiro mês) em minutos (diferença padronizada das médias [standardized mean difference, [SMD], em inglês) = −25.40; intervalo de confiança de 95% [IC95%] = −40.02- −10.78), seguido de suvorexant 20/15mg (SMD = −25.29; IC95% = −36.42- −14.15), o qual também proporcionou a maior diminuição em WASO no longo prazo (SMD = −23.70; IC95% = −35.89- −11.51). Os EAs mais frequentes foram sonolência, nasofaringite e cefaleia, com taxas de até 14.8%. Conclusão Nossos resultados sugerem que os DORAs estão associados a uma maior eficácia quando comparados com placebo no tratamento da insónia, um complexo transtorno do sono de 24 horas. Além disso, a dosagem pode desempenhar um papel importante no manejo da insónia crônica.
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ABSTRACT Background: Narcolepsy is a disease resulting from the loss of hypocretin-producing cells or other dysfunctions of the hypocretinergic system. In addition to sleep disorders, affected patients may experience increased weight gain, olfactory changes, and poorer quality of life. Methods: This study aimed to investigate the relationship between narcolepsy and weight gain, years of study, sleep parameters, and olfactory dysfunction in patients with narcolepsy type 1 and narcolepsy type 2. Anthropometric, olfactory, socioeducational, and excessive daytime sleepiness evaluations were performed in 77 patients. Results: Greater weight gain and abdominal obesity were observed in patients with type 1 narcolepsy. Patients with higher education level had lower scores of daytime sleepiness, higher scores on the olfactory function test, and lower rates of abdominal obesity. Discussion: Patients with narcolepsy type 1 showed an increased body weight and abdominal obesity when compared to narcolepsy type 2. The patients with a higher schooling level showed a reduction of the daytime sleepiness scores, lower rates of abdominal obesity, and better scores on the olfactory function test. Conclusion: Among all the patients with narcolepsy, the data indicated that aging and hypocretin deficiency are associated with abdominal obesity, while years of study is the variable that mostly influences olfaction function.
RESUMO Antecedentes: A narcolepsia é resultante da perda de células produtoras de hipocretina ou da disfunção do sistema hipocretinérgico. Além dos distúrbios do sono característicos da doença, os pacientes afetados podem apresentar também aumento de peso, alterações olfatórias e pior qualidade de vida. Métodos: O objetivo do estudo é investigar a relação entre a narcolepsia e o ganho de peso, anos de estudo, parâmetros do sono e a disfunção olfatória em pacientes com narcolepsia tipo 1 e narcolepsia tipo 2. Foram realizadas avaliações antropométricas, do olfato, sociais, educacionais e da sonolência excessiva diurna nos 77 indivíduos participantes da pesquisa. Resultados: Foram observados, nos pacientes com narcolepsia tipo 1, maior ganho de peso e maior frequência de obesidade central. Pacientes com ensino superior apresentaram escores mais baixos de sonolência excessiva diurna, escores mais altos no teste de função olfatória e menores taxas de obesidade central. Discussão: Pacientes com narcolepsia tipo 1 apresentaram maior ganho de peso e obesidade central quando comparados aos com narcolepsia tipo 2. Os pacientes com maior escolaridade apresentaram menores escores de sonolência diurna, de obesidade central e melhores escores no teste da função olfatória. Conclusão: Nos indivíduos com narcolepsia tipo 1 e tipo 2, os dados indicaram que o envelhecimento e a deficiência de hipocretina estão associados à obesidade central, enquanto anos de estudo é a variável que mais influencia na função olfatória.
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Humanos , Neuropéptidos , Obesidad Abdominal/complicaciones , Narcolepsia , Calidad de Vida , Envejecimiento , Péptidos y Proteínas de Señalización Intracelular , OrexinasRESUMEN
Objective To analyze the correlation between serum orexin-A (OXA) and early postoperative cognitive function in elderly patients undergoing lumbar spinal surgery under general anesthesia. Methods A total of 76 elderly patients (age ≥65 years) underwent lumbar spine surgery under general anesthesia from December 2018 to December 2019 in the Affiliated Hospital of Inner Mongolia Medical University were collected. All the enrolled patients were evaluated by the same doctor with the Montreal cognitive assessment scale (MoCA) on one day before the surgery and one to three days after the surgery, and venous blood was extracted from the patient on the operation day and one day after the operation, and the serum levels of OXA and S100β were measured by ELISA. According to the results of cognitive function assessment, the patients were divided into postoperative cognitive dysfunction (POCD) group and non-postoperative cognitive dysfunction (NPOCD) group. The differences in serum OXA and S100β protein levels between the two groups and their correlation with MoCA scores were statistically analyzed. Results There was no statistically significant difference in the MoCA score, serum OXA level, and S100β protein level before surgery, and heart rate (HR), mean artery pressure (MAP), bispectral index (BIS) and pulse oxygen saturation (SpO2) levels before anesthesia induction (T0), at the start of surgery (T1), at 1h after the start of surgery (T2), at the withdrawal time (T3), and at 15 minutes after extubation (T4) between the two groups (P>0.05). At the first, second, and third day after operation, the MoCA scores of the POCD group were lower than those before the operation, and they were both lower than those of the NPOCD group, the difference was statistically significant (P<0.001). There was a statistically significant difference in serum OXA levels between the two groups after the operation (P<0.05). The postoperative S100β protein level was higher than that before the operation in the two groups, and the POCD group increased more significantly, the difference between the two groups after the operation was statistically significant (P<0.05). The postoperative OXA level was positively correlated with the MoCA score (r=0.545, 0.531, 0.779) and negatively correlated with the S100β protein level (r=-0.591, -0.362, -0.743) in the two groups, and the difference was statistically significant (P<0.05). Conclusions The level of serum OXA is positively correlated with early postoperative cognitive function in elderly patients undergoing lumbal spine surgery under general anesthesia, suggesting that OXA may be a potential target for reducing the risk of postoperative cognitive dysfunction in such patients, so as to provide new ideas for preventing and improving the postoperative cognitive dysfunction in elderly patients in the future.
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Objective To investigate the effects of orexin-A on firing activity of gastric distensionsensitive (GD) neurons in the basomedial amygdala (BMA) and food intake in diet-indaced obese rats.Methods Healthy male Wistar rats were selected,and the diet-induced obesity (DIO) rat model and dietinduced resistant (DR) rat model were established by high-fat diet.The effects of orexin-A and an opioid receptor antagonist naloxone on BMA GD neurons were observed by recording the extracellular potentials of single neurons.The effects of orexin-A and naloxone on the food intake of different rats were observed by using BMA catheterization.The mRNA expression and protein expression of orexin-1 receptor (OX-1R) and μ opioid receptor were detected by real-time PCR and Elisa,respectively.Results After microinjection of orexinA into the BMA,the firing frequency of GD-sensitive neurons in the normal rats was significantly increased (GD-E:(78.3±6.9)％,GD-Ⅰ:(55.5±4.7) ％,P＜0.01),and this effect was completely blocked by OX-1R receptor antagonist SB334867,and naloxone partially blocked the discharge-promoting effect of orexin-A;Compared with the normal rats,the firing frequency of GD-sensitive neurons in the DIO (GD-E:(91.6±7.1) ％,GD-Ⅰ:(67.9±8.1) ％) and DR(GD-E:(87.9±6.8) ％,GD-Ⅰ:(69.2±5.8) ％) rats was significantly increased after BMA injection of orexin-A (P＜0.05).After administration of orexin-A into the BMA,food intake of the normal rats,DIO rats and DR rats ((2.38±0.34) g,(3.75 ±0.32) g,(4.01 ±0.38) g,respectively) was significantly increased (P＜0.01),and the food intake of DR and DIO rats were significantly higher than that of normal rats (P＜0.05).After BMA was injected with naloxone,the food intake of rats was inhibited,and the food intake of the DIO rats was significantly lower than that of the DR rats (P＜0.05),food intake of the DR rats was significantly lower than that of the normal rats (P＜0.05).The results of real-time PCR showed that the mRNA levels of OX-1R in DIO and DR rats were(5.85±0.45)and (6.03±0.42)were higher than that of normal rats,and the difference was significant (P＜0.05);and mRNA levels of μ-opioid receptors in DIO and DR rats((4.51±0.42) and (8.31±0.41) times) were higher than those in normal rats (P＜0.05).The results of Elisa showed that the protein levels of OX-1R in DIO ((2.98±0.28) ng/μl)and DR rats ((3.05±0.31) ng/μl) were higher than those in normal rats ((1.53±0.31) ng/μl,P＜0.05).The content of μ-opioid receptor protein in DR rats ((4.21±0.35) ng/μl) was higher than that of DIO rats ((2.77±0.27) ng/μl),and higher than that of normal rats((1.48±0.32) ng/μ),the difference was significant (P＜0.05).Conclusion BMA orexin-A promotes the spontaneous discharge of GD-sensitive neurons and food intake in normal rats,DIO rats and DR rats,μ-opioid receptors may be involved in the regulation of this process.
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BACKGROUND: The trigeminal nucleus caudalis (Vc) is a primary central site for trigeminal transmitting. Noxious stimulation of the trigeminal nociceptors alters the central synaptic releases and neural expression of some inflammatory and trophic agents. Orexin-A and the orexin 1 receptor (OX1R) are expressed in pain pathways including trigeminal pain transmission. However, the the mechanism(s) underling orexin-A effects on trigeminal pain modulation have not been fully clarified. METHODS: Trigeminal pain was induced by subcutaneous injection of capsaicin in the upper lip in rats. The effect of trigeminal pain on cyclooxygenase-2 (COX-2) and brain-derived neurotrophic factor (BDNF) expression in the Vc of animals was determined by immunofluorescence. Subsequently, OX1R agonist (orexin-A) and antagonist (SB-334867-A) was administrated in the Vc to investigate the possible roles of the Vc OX1R on changes in COX-2 and BDNF levels following pain induction. RESULTS: The data indicated an increase in COX-2 and decrease in BDNF immuno-reactivity in the Vc of capsaicin, and capsaicin- pretreated with SB-334867-A (80 nM), groups of rat. However, the effect of capsaicin on COX-2 and BDNF expressions was reversed by a Vc microinjection of orexin-A (100 pM). CONCLUSIONS: Overall, the present data reveals that orexin-A can attenuate capsaicin-induced trigeminal pain through the modulation of pain effects on COX-2 and BDNF expressions in the Vc of rats.
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Animales , Ratas , Factor Neurotrófico Derivado del Encéfalo , Capsaicina , Ciclooxigenasa 2 , Dolor Facial , Técnica del Anticuerpo Fluorescente , Inyecciones Subcutáneas , Labio , Microinyecciones , Nociceptores , Antagonistas de los Receptores de Orexina , Orexinas , Dimensión del Dolor , Percepción del Dolor , Núcleo Caudal del Trigémino , Neuralgia del Trigémino , Núcleos del TrigéminoRESUMEN
Objective To investigate the wake-promoting action of median nerve electrical stimulation(MNES) in coma rats induced by traumatic brain injury(TBI) and its influence on the expression of α1-adrenergic receptor(α1 R) in the prefrontal contex (PFC).Methods Seventy-two healthy Sprague Dawley(SD) rats were randomly divided into the control group,sham-stimulated group(TBI),stimulated group (TBI+ MNES) and antagonist group(TBI+ OX1R antagonist +MNES).The control group had no any treatment.The TBI coma rat models were prepared in the other 3 groups.The sham stimulated group had no treatment.The antagonist group was injected with orexin receptor-l(OX1R) antagonist SB334867 into lateral ventricle,and both the antagonist group and stimulated group received MNES treatment.Then the behavior changes of rats in each group were observed and the α1 R expression level in PFC was detected by using the immunohistochemistry technique.Results Thirteen rats in the stimulated group and 8 rats in the antagonist group revived,while only 4 rats in the TBI group.The α1R levels from low to high were the blank control group,sham-stimulated group,antagonist group and stimulated group,showing the increasing trend,and the difference was statistically significant(P＜0.05).Conclusion MNES can improve the rat consciousness level after TBI coma,and its mechanism may be related with up-regulating the α1 R expression level in PFC area,moreover Orexin-A participates in this regulation process.
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Objective To investigate the expression of H1 protein in the prefrontal cortex of comatose rats which have suffered traumatic brain injury (TBI) after electrical stimulation of the median nerve (MNS).Methods Seventy-two Sprague-Dawley rats (weighing 250 to 300 g) were randomly divided into a stimulated group (MNS+ TBI),an antagonist group (MNS+TBI+OXR1 antagonist),a model group (TBI) and a control group,with 18 rats in each group.Traumatic brain injury was modeled in all of the rats except those of the control group.After the modeling,the stimulated group was given MNS,the antagonist group was provided with MNS and an OXR1 injection,and the model group was given MNS with a current intensity of 0.One hour after the experiment,the consciousness of each rat was evaluated using a double-blind method.Animals were sacrificed at 6,12 and 24 hours after the intervention and brain tissue was removed.H1 protein expression was examined using immunohistochemistry.Results One hour after the experiment,significant differences were observed in the consciousness of the 4 groups,with the 18 rats of the control group on consciousness level one.Thirteen rats in the stimulated group exhibited a righting reflex,compared with 9 in the antagonist group and 5 in the model group.Immunohistochemistry showed that H1 expression was strongest in the stimulated group,followed by the antagonist,control and model groups.The H1 expression was highest at 24 hours after the experiment,followed by that at 6 h and 12 h,but those differences were not statistically significant.Conclusion Median nerve electrical stimulation might modulate wakefulness after traumatic brain injury by promoting H1 expression via orexin-A in the prefrontal contex.
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Objective:To investigate the expression of 5-HT 2A receptor in the prefrontal cortex of traumatic brain injuryinduced coma rats after median nerve electrical stimulation.Method:A total of 72 SD rats (weighing 250-300g) were randomly divided into 4 groups:a stimulationgroup,an antagonist group,a sham-stimulation group and a control group.This traumatic brain injury model was established by a weight-drop head injury,and we evaluated the change of behavior through the six classical levels of consciousness.The animals were sacrificed and their brain tissues were removed at 6,12,and 24 hours after injury.5-HT 2A protein expression was examined by immunohistochemistry.Result:Thirteen rats exhibited righting reflex in the stimulation group.In the antagonist group,9 rats exhibited righting reflex.5 rats in the sham-stimulation group had the same response.The mean rank of consciousness degree were degree 9.50 in the control group,degree 52.75 in the sham-stimulation group,degree 37.61 in the stimulation group,degree 46.14 in the antagonist group.Comparison among groups presented an increasing consciousness degree:control group＜stimulation group＜antagonist group＜sham-stimulation group(P＜0.01).Resuits from immunohistochemistry showed that significant differences in the 5-HT 2A expression among the four groups (sham-stimulation＜control＜antagonist＜stimulation))(P＜0.05),and a within-group comparison showed that the 5-HT 2A expression level was as follows:6 hours＜24 hours ＜12 hours(P＜0.05).Conclusion:Median nerve electrical stimulation might modulate wakefulness by promoting the 5-HT 2A expression via orexin-A in the prefrontal cortex of rats with traumatic brain injury-induced coma.
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Objective To provide new evidences for understanding the mechanisms of promo-tive role of orexins in anesthetic emergence and the effect of microinjection of orexin-A/orexin-B into cerebral ventricle on the release of histamine.Methods Male SD rats were randomly divided into sa-line (control ), orexin-A and orexin-B groups. The microdialysis probe was inserted into hypothalamus under stereotaxic apparatus.The perfused fluid from the area of hypothalamic tube-romammillary nucleus was collected using in vivo microdialysis at 1 h,2 h and 3 h after 1 nmol or 5 nmol orexin-A or orexin-B microinjection into the cerebral ventricle (n =5 each).The concentrations of histamine at each time point in dialysates of perfused fluid were detected by high performance liquid chromatography (HPLC)to analyze its dynamic changes.After one week,each group was microin-jected with 10 nmol,15 nmol and 20 nmol orexin-A and orexin-B (n =5)into the cerebral ventricle respectively,dialysates was collect and histamine was detected at 1 h to analyze its dosage response. After one week,each group was microinjected 0.3 μl saline orexin-A and orexin-B (n =6)into the tu-beromammillary nucleus.Results Compared with the control group,microinjection of 1 nmol orexin-A significantly increased histamine release at 1 h,but the same dose of orexin-B had no such effect,5 nmol of orexin-A or orexin-B injections significantly facilitated histamine release at 2 h and 3 h (P <0.01).Microinjection of 10 nmol,15 nmol and 20 nmol orexin-A and orexin-B into ventricle caused an significant increase of histamine release at 1 h while the effect was the strongest in 20 nmol (P <0.05).Compared with the control group,microinjection of orexin-A significantly decreased time of the righting reflex (P <0.01),but the same dose of orexin-B had no such effect.Conclusion Micro-injection of both orexin-A or orexin-B into cerebral ventricle could promote the release of histamine, while the effect of orexin-A was stronger.Microinjection orexin-A into tuberomammillary nucleus sig-nificant facilitated recovery from isoflurane.
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Objective To explore the effect of vagus nerve stimualtion on wake-promoting and the expression of 5-hydroxytryptamine (5-HT) 2A receptor in the prefrontal contex of coma rats with traumatic brain injury. Methods 72 Sprague-Dawley rats were randomly divid-ed into control group, sham-stimulated group, stimulated group and antagonist group with 18 rats in each group. Traumatic brain injury mod-el was established by a weight-drop head injury. The antagonist group was injected with SB334867, and both the antagonist group and the stimulated group received vagus nerve stimulation. Their behaviors were recorded. And immunohistochemistry technique was used to detect the expression of 5-HT2A receptor in the prefrontal cortex. Results 12 rats in the stimulated group, 9 in the antagonist group and 4 in the sham-stimulated woke up. The expression of 5-HT2A receptor from low to high was ranged as the control group, the antagonist group, the sham-stimulated group and the stimulated group (χ2=11.464, P=0.009). Conclusion Vagus nerve stimulation could raise consciousness in co-ma rats after traumatic brain injury, which may be related to up-regulating the expression of 5-HT2A receptor.
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The cytoprotective enzyme heme oxygenase-1 (HO-1) influences endothelial cell survival, proliferation, inflammatory response, and angiogenesis in response to various angiogenic stimuli. In this study, we investigate the involvement of HO-1 in the angiogenic activity of orexin-A. We showed that orexin-A stimulates expression and activity of HO-1 in human umbilical vein endothelial cells (HUVECs). Furthermore, we showed that inhibition of HO-1 by tin (Sn) protoporphryin-IX (SnPP) reduced orexin-A-induced angiogenesis in vivo and ex vivo. Orexin-A-stimulated endothelial tube formation and chemotactic activity were also blocked in SnPP-treated vascular endothelial cells. Orexin-A treatment increased the expression of nuclear factor erythroid-derived 2 related factor 2 (Nrf2), and antioxidant response element (ARE) luciferase activity, leading to induction of HO-1. Collectively, these findings indicate that HO-1 plays a role as an important mediator of orexin-A-induced angiogenesis, and provide new possibilities for therapeutic approaches in pathophysiological conditions associated with angiogenesis.
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Elementos de Respuesta Antioxidante , Células Endoteliales , Hemo-Oxigenasa 1 , Células Endoteliales de la Vena Umbilical Humana , Luciferasas , Estaño , OrexinasRESUMEN
Obejective To explore the correlation of Orexin A and respiratory drive in chronic obstructive pulmo-nary disease (COPD) patients. Methods Pulmonary function was tested in 30 stable COPD patients and 20 normal healthy adults. Plasma orexin A level was measured with a radioimmunoassay kit. The correlation of Orexin A with BMI, age, BDI, FEV1, FVC, FEV1/FVC, MEP, MIP, P0.1 in COPD patients was analyzed. Results Plasma Orexin A levels in patients with COPD group(1.87±0.43)ng/L was higher than those in the control group(1.49±0.19)ng/L, P<0.01. Plasma Orexin A lev-els in patients with COPD correlated negatively with FEV1(r=-0.389,P < 0.05),and correlated positively with P0.1(r=0.728,P<0.01). Conclusion Plasma orexin A in COPD patients increased which may be caused by smoking and hyper-capnia. Orexin A may play a crucial role in regulating respiratory drive in COPD patients.
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Objective To explore the changes of plasma orexin-A level before and after operation in obstructive sleep apnea-hypopnea syndrome(OSAHS) children and its effect on their behavior performance.Methods 120 cases OSAHS children performed tonsillectomy and / or adenoidectomy and 30 cases normal children as control group.According to the AHI index,the OSAHS group was divided into mild group (5 times/h ≤ AHI ＜ 20times/h,n=13),moderate group (20/h ≤ AHI ＜40/h,n=76),and severe group (AHI ≥ 40 times / h,n=31).And at the same time,according to the sensory integration ratings,OSAHS group was divided into normal group(n =30),mildly abnormal group (n =47),moderately abnormal group (n =28),severely abnormal group (n =15).Before operation and 6 months after operation,plasma orexin-A levels and children's sensory integration were measured.Results Plasma orexin-A level of the OSAHS group ((0.41 ± 0.06) μg/ml) was significantly higher compared with the control group((0.31±0.04) μg/ml) (P＜0.01).In orexin-A level of different AHI groups before and after operation(mild group:(0.33±0.02) μg/ml vs (0.28± 0.03) μg/ml,moderate group:(0.39±0.04) μg/ml vs (0.29±0.03) μg/ml,severe group:(0.49±0.04) μg/ml vs (0.32± 0.02) μg/ml),there had significant differences (P＜0.01).In OSAHS children,AHI index had positive correlation with preoperative plasma orexin-A level (r=0.803,P＜0.01).There was a significant negative correlation between sensory integration scores and plasma orexinA level(r=-0.812,P＜0.01).Conclusions Plasma orexin-A level of OSAHS children is closely related to the severity of OSAHS and the changes of their behavioral ability.And it may become a diagnostic plasma marker of OSAHS children.
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Objective To investigate the effects of orexin-A on learning and memory of pentyleneterazol (PTZ)-kindled epileptic rats.Methods Adult Wistar rats were randomly divided into control group(normal saline,NS)and PTZ group.The PTZ-kindled rats were randomly divided into,orexin-A group and NS group administrated by intracerebroventricular(i.c.v.)injection of 10μl orexin-A(1.4 nmol/μl)or 10μl NS.Using Morris water msze experiment,the ability of learning and memory was measured in all rats.Results Eighty percent of rats in PIZ group were kindled successfully after intraperitoneal injection of 35mg/kg PTZ every day for 30 days.Compared to control group,the escape latency in the PTZ-kindled rats was significantly increased in place navigation test(PNT)(F=200.956,P<0.01),whereas a remarkable reduction of time spent in the target quadrant and number of pool circlings in 120 seconds Was observed during probe trials.Following injection of orexin-A,the latency of escape platform was significantly declined in both PTZ-kindled((39.73±2.03)8,(33.76±2.96)s)and NS rats,increased the number of crossing the platform(10.83±1.80)vs(4.67±3.34).In addition,the treatment with orexin-A markedly increased swim velocity and number of pool circlings in beth groups(P<0.01),particularly to the PTZ-kindled rats.Conclusion Spatial learning and memory in the PIZ-kindled rats can be improved by treatment with orexin-A.
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Objective To observe the impact of Angong Niuhuang Wan(安宫牛黄丸) on orexin-A,neuropeptide Y(NPY) and Leptin in patients with obstructive sleep apnea-hypopnea syndrome(OSAHS).Methods Total 50 mild and moderate cases of OSAHS which were definitely diagnosed by the results of polysomnogram′s monitoring were selected and randomly divided into treatment group and control group(each n=25).The treatment group took one pill of Angong Niuhuang Wan everyday before sleep for 30 days,while the control group received no treatment.Then the levels of orexin-A,NPY and Leptin were tested by radio-immune assay and enzyme linked immunosorbent assay(ELISA) to compare the changes of 3 indexes before and after the treatment and compare the result differences between the two groups.Results Compared with the control group,after treatment,apnea hypopnea index(AHI) and arousal index of treatment group were obviously decreased((16.33?3.57) times/h vs.(22.23?9.98) times/h,(103.58?32.90) times/s vs.(127.89?42.78) times/s),the average pulse oximetric saturation(MSpO2) and the lowest pulse oximetric saturation(LSpO2) were significantly increased(0.950?0.032 vs.0.934?0.048,0.830?0.041 vs.0.826?0.127,P0.05).The correlative analyses indicated that the levels of orexinA,Leptin and NPY in the patients of OSAHS had positive correlations with AHI(r1=0.445,r2=0.480,r3=0.454) and awareness index(r1=0.613,r2=0.510,r3=0.479,P
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This study was aimed to investigate the changes of orexin-A (OXA) and neuropeptide Y (NPY) expression in the hypothalamus of the fasted and high-fat diet fed rats. For the experiments, the male Sprague-Dawley (SD) rats were used as the model of high-fat diet-induced obesity. The mean loss of body weight (MLBW) did not show the linear pattern during the fasting; from 24 h to 84 h of fastings, the MLBW was not significantly changed. The numbers of OXA-immunoreactive (IR) neurons were decreased at 84 h of fasting compared with those in other five fasting subgroups. The NPY immunoreactivities in the arcuate nucleus (ARC) and the suprachiasmatic nucleus (SCN) observed at 84 h of fasting were higher than that observed at 24 h of fasting. The number of OXA-IR neurons of the LHA (lateral hypothalamic area) in the high-fat (HF) diet fed group was more increased than that of the same area in the normal-fat (NF) diet fed group. The NPY immunoreactivities of the ARC and the SCN were higher in HF group than those observed in the same areas of NF group. Based on these results, it is noteworthy that the decrease of the body weight during the fast was not proportionate to the time-course, implicating a possible adaptation of the body for survival against starvation. The HF diet might activate the OXA and the NPY in the LHA to enhance food intake.
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Animales , Masculino , Ratas , Adaptación Fisiológica/fisiología , Núcleo Arqueado del Hipotálamo/metabolismo , Grasas de la Dieta , Ingestión de Alimentos , Ayuno/fisiología , Área Hipotalámica Lateral/metabolismo , Hipotálamo/metabolismo , Inmunohistoquímica/veterinaria , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neuropéptido Y/metabolismo , Neuropéptidos/metabolismo , Obesidad , Ratas Sprague-Dawley/fisiología , Núcleo Supraquiasmático/metabolismoRESUMEN
Objective To investigate the effect of exogenous orexinA on the pyramid neurons and interneurons in the prefrontal cortex prelimbic(PL)area.Methods The pyramid neurons and interneurons in PL area of Kunming mice were selected from prefrontal cortex slices by infrared visual patch clamp technique.The morphology and electrophysiological features of the pyramid neurons and interneurons were observed.The effect of exogenous orexinA at a concentration of 400 nmol/L on these cells was studied using the whole cell configuration.Results The pyramid neurons were large,pyramidal in cell body with clear apical dendrites extending vertically and several basal dendrites radiating.The interneurons were comparatively smaller and had several processes from cell body.In current clamp mode,all 54 pyramid neurons having been recorded showed frequency adaption,and the 15 recorded interneurons discharged rapidly and had no frequency adaption.While in vol-tage clamp mode,36 pyramid neurons were regarded as Ih(+)pyramid neurons for recorded hyperpolariztion-activated cation current,and the left 18 and 15 interneurons were Ih(-).Exogenous orexinA had a total reaction rate of 51.9% on 54 recorded pyramid neurons under current clamp,and a rate of 66.7% on 36 Ih(+)pyramid neurons and of 22.2% on the Ih(-)pyramid neurons under voltage clamp.All 15 recorded interneurons had no reaction to exogenous orexinA under either mode.Conclusion OrexinA plays excitatory effect on pyramid neurons in the prefrontal cortex PL area,and this effect is much more noticeable in pyramid neurons with Ih currents.
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Objective To explore the change of plasma orexin-A levels in patients with chronic obstructive pulmonary disease(COPD).Methods Lung function test and blood gas analysis were performed in 15 obese COPD patients,20 COPD patients without obesity,20 obese controls and 20 normal healthy adults(control group).In both obese COPD group and obese group,the body mass index(BMI)was higher than 25 and there was no significant difference in BMI.The plasma was deproteinized by chromatography,and the plasma orexin-A levels were determined by radioimmunoassay.Results The plasma orexin-A levels in the obese COPD group[(8.82?1.90)ng/L]and the non-obese COPD group[(8.69?1.84)ng/L]were significantly higher than those in the obese group[(7.18?1.45)ng/L(P 0.05).Plasma orexin-A levels in patients with COPD correlated negatively with partial pressure of oxygen(PaO_2)(r = -0.527 ,P