Orexins (or hypocretins) are hypothalamic neuropeptides with a multitude of physiological functions. They occur in two known forms, namely, orexin A and orexin B with a common precursor, preproorexin. The orexin recep...Orexins (or hypocretins) are hypothalamic neuropeptides with a multitude of physiological functions. They occur in two known forms, namely, orexin A and orexin B with a common precursor, preproorexin. The orexin receptors (orexin 1R and orexin 2R) belong to the Family of G-protein coupled receptors. The primary function of the orexin system,i.e. the orexins, their receptors and associated neuronal circuitries, perhaps is to increase spontaneous physical activity and food intake, thereby promoting an increase in energy expenditure. Reports suggest that orexins may be the key brain components to mediate the mechanism of obesity resistance. Recent research also has thrown lights upon a significant role of orexins, especially orexin A, in regulation of male reproductive functions owing to their receptor expressions in vital testicular cells, such as Leydig cells, Sertoli cells as well as spermatozoa at different developmental stages, even in the epididymis and penis. Moreover, orexins have been reported to greatly influence gonadotropin-releasing hormone neurons and their secretions to regulate reproductive functionsvia modulation of the hypothalamic-pituitary-gonadal axis. Evidence thus implicates participation of orexins in steroidogenesis, spermatogenesis, transportation and maturation of sperm as well as in the control of penile function. However, further research is required in this direction to elucidate the mechanisms by which orexins play a role in different testicular functions and effect of orexins on semen quality.展开更多
Inflammation and lung function decline are the main pathophysiological features of chronic obstructive pulmonary disease （COPD）. Acupuncture can improve lung function in patients with COPD, but the underlying mechan...Inflammation and lung function decline are the main pathophysiological features of chronic obstructive pulmonary disease （COPD）. Acupuncture can improve lung function in patients with COPD, but the underlying mechanisms are not well understood. Orexins （OXs）, which are found in peripheral plasma, are neuropeptides that regulate respiration and their levels are related to COPD. Therefore, we hypothesized that acupuncture might alter OXs, reduce lung inflammation and improve lung function in COPD. METHODS： COPD was induced in rats by exposure to cigarette smoke for 8 weeks and injecting with lipopolysaccharide twice. Electroacupuncture （EA） was performed at Feishu （BL13） and Zusanli （ST36） for 30 min/d for 2 weeks. Rat lung function and morphology were assessed after EA. The levels of tumor necrosis factor-α （TNF-a） and intedeukin-1β （IL-16） in bronchoalveolar lavage fluid （BALF） and orexin A and B levels in the lung tissue were detected by enzyme-linked immunosorbent assay. OX receptor mRNA levels and immunopositive cells were assessed with real-time polymerase chain reaction and immunohistochemical methods, respectively. The relationships among lung function, cell factors, and OX levels were analyzed by Pearson correlation analyses. RESULTS： Compared with the control group, lung function was significantly decreased in the rats with COPD （P〈0.05）. There were obvious increases in TNF-α and IL-1β levels in BALF （P〈0.05 and P〈0.01, respectively）, orexin A level in lung tissue （P〈0.01; but not orexin B） and mRNA expressions of OX 1 type receptor （OXR1） and OX 2 type receptor （OXR2） in lung tissue （P〈0.05 and P〈0.01, respectively）; the integrative optical densities （IODs） of both receptors were greater in the COPD group （P〈0.05）. For rats with COPD subjected to EA, lung function was improved （P〈0.05）. There were notable decreases in TNF-a and IL-1β levels （P〈0.05 and 〈0.01, respectively） in BALF. Orexin A, but not orexin B, levels in lung tissue also decreased （P〈0.01）, as did mRNA expression of OXlR and OX2R in lung tissue （P〈0.05 and P〈0.01, respectively）. Receptor IODs were also reduced after EA treatment （P〈0.05）. Furthermore, orexin A levels and ratio of forced expiratory volume in 0.3 s to forced vital capacity were strongly negatively correlated （P〈0.01）, and orexin A was positively correlated with TNF-α and IL-1β （P〈0.001 and P〈0.05, respectively）.CONCLUSION： EA at Zusanli and Feishu improved lung function of rats with COPD and had an anti-inflammatory effect, which may be related to down-regulation of OXA and its receptors.展开更多
Hypothalamic neuropeptides named hypocretin/orexins which were identified in 1998 regulate critical functions such as wakefulness in the central nervous system.These past 20 years had revealed that orexins/receptors s...Hypothalamic neuropeptides named hypocretin/orexins which were identified in 1998 regulate critical functions such as wakefulness in the central nervous system.These past 20 years had revealed that orexins/receptors system was also present in the peripheral nervous system where they participated to the regulation of multiple functions including blood pressure regulation,intestinal motility,hormone secretion,lipolyze and reproduction functions.Associated to these peripheral functions,it was found that orexins and their receptors were involved in various diseases such as acute/chronic inflammation,metabolic syndrome and cancers.The present review suggests that orexins or the orexin neural circuitry represent potential therapeutic targets for the treatment of multiple pathologies related to inflammation including intestinal bowel disease,multiple sclerosis and septic shock,obesity and digestive cancers.展开更多
选取苏钟种母猪16头,在第2个发情期后,按发情前期、发情期、发情后期和间情期随机分成4组。用RT-PCR检测苏钟猪发情周期不同时期preproorexin和orexin 1受体(OX1R) m RNA在下丘脑-垂体-卵巢轴中的表达。结果显示:发情周期不同时期prepro...选取苏钟种母猪16头,在第2个发情期后,按发情前期、发情期、发情后期和间情期随机分成4组。用RT-PCR检测苏钟猪发情周期不同时期preproorexin和orexin 1受体(OX1R) m RNA在下丘脑-垂体-卵巢轴中的表达。结果显示:发情周期不同时期preproorexin m RNA在下丘脑、垂体和卵巢中变化趋势一致,preproorexin m RNA在猪的发情前期表达最高,随后其表达量开始下降,在发情后期其表达最少,在间情期时又开始上升。下丘脑中OX1R m RNA在发情前期开始上升,在发情后期达到最高,随后在间情期又开始下降。垂体和卵巢中OX1 R m RNA的变化与下丘脑中OX1R m RNA的变化趋势一致。上述结果表明:orexin可能参与调控动物生殖过程。展开更多
目的 研究Orexin- A m RNA表达在体内主要脏器的分布及在急性炎症损伤后的变化,探讨Orexin- A在急性炎症反应中的作用。方法 取正常雄性SD大鼠和肠缺血再灌注(IR)损伤模型大鼠的下丘脑、胃、肺、肾、附睾脂肪垫、睾丸、肝、脾、十二...目的 研究Orexin- A m RNA表达在体内主要脏器的分布及在急性炎症损伤后的变化,探讨Orexin- A在急性炎症反应中的作用。方法 取正常雄性SD大鼠和肠缺血再灌注(IR)损伤模型大鼠的下丘脑、胃、肺、肾、附睾脂肪垫、睾丸、肝、脾、十二指肠等主要脏器,采用逆转录聚合酶链反应(RT- PCR)检测Orexin- A m RNA在各主要脏器的分布情况,同时检测IR损伤后下丘脑内Orexin- A m RNA的表达变化。结果 所取各脏器均有Orexin -A m RNA表达,尤其是在胃、肺、肾的表达丰度较高。在IR损伤的急性刺激作用后,下丘脑Orexin- A m RNA表达水平出现波动式的下降趋势。结论 Orexin- A m RNA广泛分布于机体主要脏器,对急性炎症刺激具有时间依赖性的应答效应,其表达水平变化可以作为一种新型的急性炎症反应监测指标。展开更多
目的研究侧脑室注射不同剂量orexin2A对麻醉大鼠脑电图(electroencephalogram,EEG)、翻正反射消失(loss of righting reflex,LRR)持续时间、共济失调等的影响。方法腹腔注射氯胺酮75mg/kg及咪达唑仑5mg/kg麻醉大鼠后,侧脑室注射不同剂量...目的研究侧脑室注射不同剂量orexin2A对麻醉大鼠脑电图(electroencephalogram,EEG)、翻正反射消失(loss of righting reflex,LRR)持续时间、共济失调等的影响。方法腹腔注射氯胺酮75mg/kg及咪达唑仑5mg/kg麻醉大鼠后,侧脑室注射不同剂量orexin2A,通过大鼠脑电δ波比例、LRR持续时间及共济失调监测,了解不同剂量orexin2A对麻醉大鼠催醒效果。结果与对照组相比,侧脑室注射orexin2A1nmol后,大鼠脑电δ波、LRR持续时间及共济失调时间,差异无统计学意义(P>0.05);侧脑室注射orexin2A4、7、10nmol后,大鼠脑电δ波、LRR持续时间及共济失调时间,差异有统计学意义(t=22.81～36.45,P<0.01);高剂量组与超高剂量组比较,差异无统计学意义(P>0.05)。结论侧脑室注射orexin2A可使麻醉深度变浅,麻醉时间缩短,并可促进麻醉后运动功能恢复,存在一定的量效关系。展开更多
文摘Orexins (or hypocretins) are hypothalamic neuropeptides with a multitude of physiological functions. They occur in two known forms, namely, orexin A and orexin B with a common precursor, preproorexin. The orexin receptors (orexin 1R and orexin 2R) belong to the Family of G-protein coupled receptors. The primary function of the orexin system,i.e. the orexins, their receptors and associated neuronal circuitries, perhaps is to increase spontaneous physical activity and food intake, thereby promoting an increase in energy expenditure. Reports suggest that orexins may be the key brain components to mediate the mechanism of obesity resistance. Recent research also has thrown lights upon a significant role of orexins, especially orexin A, in regulation of male reproductive functions owing to their receptor expressions in vital testicular cells, such as Leydig cells, Sertoli cells as well as spermatozoa at different developmental stages, even in the epididymis and penis. Moreover, orexins have been reported to greatly influence gonadotropin-releasing hormone neurons and their secretions to regulate reproductive functionsvia modulation of the hypothalamic-pituitary-gonadal axis. Evidence thus implicates participation of orexins in steroidogenesis, spermatogenesis, transportation and maturation of sperm as well as in the control of penile function. However, further research is required in this direction to elucidate the mechanisms by which orexins play a role in different testicular functions and effect of orexins on semen quality.
基金supported by grants from the National Natural Science Foundation of China(No.81072870No.81102660+1 种基金No.81373743)Open Research Fund of Zhejiang First-foremost Key Subject-Acupuncture&Moxibustion(No.ZTK2010B06)
文摘Inflammation and lung function decline are the main pathophysiological features of chronic obstructive pulmonary disease （COPD）. Acupuncture can improve lung function in patients with COPD, but the underlying mechanisms are not well understood. Orexins （OXs）, which are found in peripheral plasma, are neuropeptides that regulate respiration and their levels are related to COPD. Therefore, we hypothesized that acupuncture might alter OXs, reduce lung inflammation and improve lung function in COPD. METHODS： COPD was induced in rats by exposure to cigarette smoke for 8 weeks and injecting with lipopolysaccharide twice. Electroacupuncture （EA） was performed at Feishu （BL13） and Zusanli （ST36） for 30 min/d for 2 weeks. Rat lung function and morphology were assessed after EA. The levels of tumor necrosis factor-α （TNF-a） and intedeukin-1β （IL-16） in bronchoalveolar lavage fluid （BALF） and orexin A and B levels in the lung tissue were detected by enzyme-linked immunosorbent assay. OX receptor mRNA levels and immunopositive cells were assessed with real-time polymerase chain reaction and immunohistochemical methods, respectively. The relationships among lung function, cell factors, and OX levels were analyzed by Pearson correlation analyses. RESULTS： Compared with the control group, lung function was significantly decreased in the rats with COPD （P〈0.05）. There were obvious increases in TNF-α and IL-1β levels in BALF （P〈0.05 and P〈0.01, respectively）, orexin A level in lung tissue （P〈0.01; but not orexin B） and mRNA expressions of OX 1 type receptor （OXR1） and OX 2 type receptor （OXR2） in lung tissue （P〈0.05 and P〈0.01, respectively）; the integrative optical densities （IODs） of both receptors were greater in the COPD group （P〈0.05）. For rats with COPD subjected to EA, lung function was improved （P〈0.05）. There were notable decreases in TNF-a and IL-1β levels （P〈0.05 and 〈0.01, respectively） in BALF. Orexin A, but not orexin B, levels in lung tissue also decreased （P〈0.01）, as did mRNA expression of OXlR and OX2R in lung tissue （P〈0.05 and P〈0.01, respectively）. Receptor IODs were also reduced after EA treatment （P〈0.05）. Furthermore, orexin A levels and ratio of forced expiratory volume in 0.3 s to forced vital capacity were strongly negatively correlated （P〈0.01）, and orexin A was positively correlated with TNF-α and IL-1β （P〈0.001 and P〈0.05, respectively）.CONCLUSION： EA at Zusanli and Feishu improved lung function of rats with COPD and had an anti-inflammatory effect, which may be related to down-regulation of OXA and its receptors.
基金INSERM U1149/The Inflammation Research Center,Inserm Transfert,The Institut National du Cancer,No.2013-213Ligue Nationale Contre le Cancer,No.R16020HH,GB/MA/CD/EP-12062and AgroParisTech(INRAE and UniversitéParis-Saclay).
文摘Hypothalamic neuropeptides named hypocretin/orexins which were identified in 1998 regulate critical functions such as wakefulness in the central nervous system.These past 20 years had revealed that orexins/receptors system was also present in the peripheral nervous system where they participated to the regulation of multiple functions including blood pressure regulation,intestinal motility,hormone secretion,lipolyze and reproduction functions.Associated to these peripheral functions,it was found that orexins and their receptors were involved in various diseases such as acute/chronic inflammation,metabolic syndrome and cancers.The present review suggests that orexins or the orexin neural circuitry represent potential therapeutic targets for the treatment of multiple pathologies related to inflammation including intestinal bowel disease,multiple sclerosis and septic shock,obesity and digestive cancers.
文摘选取苏钟种母猪16头,在第2个发情期后,按发情前期、发情期、发情后期和间情期随机分成4组。用RT-PCR检测苏钟猪发情周期不同时期preproorexin和orexin 1受体(OX1R) m RNA在下丘脑-垂体-卵巢轴中的表达。结果显示:发情周期不同时期preproorexin m RNA在下丘脑、垂体和卵巢中变化趋势一致,preproorexin m RNA在猪的发情前期表达最高,随后其表达量开始下降,在发情后期其表达最少,在间情期时又开始上升。下丘脑中OX1R m RNA在发情前期开始上升,在发情后期达到最高,随后在间情期又开始下降。垂体和卵巢中OX1 R m RNA的变化与下丘脑中OX1R m RNA的变化趋势一致。上述结果表明:orexin可能参与调控动物生殖过程。
文摘目的 研究Orexin- A m RNA表达在体内主要脏器的分布及在急性炎症损伤后的变化,探讨Orexin- A在急性炎症反应中的作用。方法 取正常雄性SD大鼠和肠缺血再灌注(IR)损伤模型大鼠的下丘脑、胃、肺、肾、附睾脂肪垫、睾丸、肝、脾、十二指肠等主要脏器,采用逆转录聚合酶链反应(RT- PCR)检测Orexin- A m RNA在各主要脏器的分布情况,同时检测IR损伤后下丘脑内Orexin- A m RNA的表达变化。结果 所取各脏器均有Orexin -A m RNA表达,尤其是在胃、肺、肾的表达丰度较高。在IR损伤的急性刺激作用后,下丘脑Orexin- A m RNA表达水平出现波动式的下降趋势。结论 Orexin- A m RNA广泛分布于机体主要脏器,对急性炎症刺激具有时间依赖性的应答效应,其表达水平变化可以作为一种新型的急性炎症反应监测指标。
文摘目的研究侧脑室注射不同剂量orexin2A对麻醉大鼠脑电图(electroencephalogram,EEG)、翻正反射消失(loss of righting reflex,LRR)持续时间、共济失调等的影响。方法腹腔注射氯胺酮75mg/kg及咪达唑仑5mg/kg麻醉大鼠后,侧脑室注射不同剂量orexin2A,通过大鼠脑电δ波比例、LRR持续时间及共济失调监测,了解不同剂量orexin2A对麻醉大鼠催醒效果。结果与对照组相比,侧脑室注射orexin2A1nmol后,大鼠脑电δ波、LRR持续时间及共济失调时间,差异无统计学意义(P>0.05);侧脑室注射orexin2A4、7、10nmol后,大鼠脑电δ波、LRR持续时间及共济失调时间,差异有统计学意义(t=22.81～36.45,P<0.01);高剂量组与超高剂量组比较,差异无统计学意义(P>0.05)。结论侧脑室注射orexin2A可使麻醉深度变浅,麻醉时间缩短,并可促进麻醉后运动功能恢复,存在一定的量效关系。
