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Objective To investigate the effect and mechanism of orexin-A(OX-A) on the expression and function of glial glutamate transporter-1(GLT-1) and delayed neuronal death (DND) in hippocampus CA1 region of transient global cerebral ischemia(tGCI) in rats. Methods The rats were randomized into sham group, model group, OX-A group and OX-A+LY294002 group. The binding and glutamate uptake of GLT-1 in hippocampal CA1 region were detected by the [3H]-glutamate labeling method. The content of glutamate in hippocampal CA1 region was determined by the glutamate quantitative kit. The pathological changes of neurons in hippocampal CA1 region were observed by Nissol, NeuN and Fluro-Jade C staining. The expressions of GLT-1, p-PI3K and p-Akt in hippocampal CA1 region were detected by Western blot. Results OX-A promoted the binding and glutamate uptake of GLT-1, increased glutamate content, GLT-1 expression and PI3K/AKT signaling activity, and inhibited DND in the hippocampal CA1 region of tGCI rats (P＜0.05); However, LY294002 attenuated the above therapeutic effects of OX-A(P＜0.05). Conclusions OX-A can increase the expression and function of GLT-1 and reduce DND in the hippocampal CA1 region of tGCI rats by enhancing the activity of I3K/AKT signal.

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Objective: To investigate the effect of orexin-A in Vagus nerve complex (DVC) on cisplatin-induced gastric dysftmction and its possible mechanism. Methods: Thirty rats were randomly selected and divided into 3 groups (n=10) : control group (NS group); 24 h cisplatin-treated group; 48 hcisplatin-treated group. Rats in the 24 h cisplatin-treated group and the 48h cisplatin-treated group were sacrificed 24 h and 48 h after intraperitoneal injection of cisplatin. Rats in the control group were intraperitoneally injected with normal saline (NS). Quantitative real-time PCR was used to measure the expression of orexin-A mRNA in hypothalamus of each group of rats. The concentration of substance P in cerebrospinal fluid of rats was measured by E LISA; After microinjection of orexin-A and ghrelin receptor antagonists into DVC, the intake of rat food and kaolin was measured in cisplatin treated rats. Results: Cisplatin significantly reduced or exin-A mRNA expression in the hypothalamus, and cisplatin increases the concentration of substance Pin the cere-brospinal fluid of rats . Exogenous or exin-A improve cisplatin-induced anorexia and pica. The effects of above or exin-A can be partially blocked by pre-injection of ghrelin receptor antagonists in DVC .Conclusion: Orexin-A may improve the gastric dysfunction induced by cisplatin during chemotherapy through the ghrelin neuropeptide system. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of the cannabinoid type 1 receptor (CB1) inhibitor rimonabant on the energy metabolism and related behavioral changes induced by microinjection of orexin-A into the lateral hypothalamic area (LHA). Methods: Microinjection of rimonabant into the lateral ventricle (icv) and microinjection of orexin-A into LHA were used to measure changes in energy metabolism, autonomous movement, dopamine release in the amygdala (CeA), and changes in food intake in mice. Results: The results showed that microinjection of rimonabant into lateral ventricle could attenuate the changes of energy metabolism induced by microinjection of orexin-A into LHA, decrease the spontaneous movement of mice, and weaken the ability of dopamine release in CeA of mice. Rimonabant injection of (icv) did not change the increase of food intake induced by microinjection of orexin-A into LHA. In addition, it was found that bilateral injection of rimonabant into LHA could block the promoting effect of orexin-A injection into LHA on exercise activity, but did not affect the food intake of mice. Conclusions: Cannabinoid receptors are involved in orexin-A-induced regulation of dopaminergic system activation in the midbrain system of mice, and have an effect on energy metabolism and autonomic movement, but have no significant effect on food intake regulation. [ABSTRACT FROM AUTHOR]

Objective: To study the effect of orexin-A on the feeding and gastric motility of rats in paraventricular nucleus and its regulatory mechanism. Methods: The expression of PVN orexin receptor was observed by immunohistochemistry. The changes of food intake, gastric motility, gastric acid secretion and gastric emptying were observed after PVN injection of orexin-A. Results: Immunohisto­chemistry showed orexin receptor-positive immunoreactive cells in the PVN of rats. After PVN injection of orexin-A, the feeding of rats increased in the first three hours, and there was no significant change in 6h and 24 h. After microinjection of orexin-A into PVN, the gas­tric motility amplitude and frequency, gastric emptying and gastric acid secretion of rats were increased. [D-Lys-3]-GHRP-6 partially blocked the promotion of food intake, gastric motility, gastric emptying and gastric acid secretion by orexin-A. SB334867 completely blocked the promotion of orexin-A on gastric motility, gastric emptying and gastric acid secretion. Conclusion: Orexin-A in the hypotha­lamic paraventricular nucleus could regulate the feeding and gastric function through GHSR receptor signaling pathway. [ABSTRACT FROM AUTHOR]

Objective: To explore the effect of microinjection of orexin-A into vagal complex(DVC) on the gastric function of rats. Methods: Orexin-A was microinjected into the DVC, the changes of gastric motility and gastric juice or gastric acid secretion were observed. Results: After the microinjection of orexin-A into DVC, the amplitude and frequency of gastric motility were signi覱cantly increased in a dose-dependent manner. SB334867 prevented Orexin-A-induced changes of gastric motility(P0.05). After the microinjection of orexin-A into DVC, the secretion of gastric juice and gastric acid were significantly increased in a dose-dependent manner(P0.05). Conclusion: Orexin-A could affect gastric motility and the secretion of gastric fluid. [ABSTRACT FROM AUTHOR]

Objective: To study the regulation of orexin on the gastric afferent information in the septal nuclei of rats. Methods: 138 adult male Wistar rats weighed 250-300 g were selected, extracellular discharges of single unit neuron in the septal nuclei were used to identify the gastric distension(GD) sensitive neurons. Microinjection of orexin-A or orexin-A receptor antagonist SB334867 into septal nuclei was performed to explore the changes of GD sensitive neurons in the septal nuclei. The effects of different concentrations of orexin- A on the gastric motility of rats were observed. Results: The gastric motility experiments showed that administration of orexin-A in the septal nuclei could significantly increase the amplitude and frequency of gastric motility in a dose-dependent manner (P<0.05-0.01). Microinjection of SB-334867 could completely block the effect of orexin-A on the gastric motility. After the septal nuclei Microinjection of orexin-A, there were 36 GD excitatory (GD-E) neurons and 16 GD inhibitory (GD-I) neurons. The effects induced by orexin-A on GD sensitive neurons were completely abolished with administration of SB-334867. Conclusion: Injection of orexin into the septal nuclei could promote the gastric motility in rats and also change the discharge activity of gastric distention (GD) sensitive neurons. [ABSTRACT FROM AUTHOR]

Objective: To explore the effects and the potential regulation mechanisms of orexin-A and the neural pathways between lateral nucleus (LHA) and nucleus accumbens (NAcc) on gastric motility. Methods: Adult male wiatar rats were used, and randomly divided into two parts. We used retrograde tracing and fluorescent -immunohistochemistry staining method to observe the neural pathways between lateral nucleus (LHA) and nucleus accumbens (NAcc) in the first part of rats. We used gastric motility recording in vivo to observe the change of the amplitude and frequency of gastric constriction following by nucleus accumbens micinject differents levels of orexin-A, and the change of gastric motility after electrical stimulated lateral nucleus in the two part of rats. Results: Retrograde tracing and fluorescent immunohistochemistry study shown that orexin-A/ fluorogold (FG) dual labelled neurons were found in the lateral nucleus. Gastric motility study illustrated that orexin-A microinject to the nucleus accumbens, the amplitude and frequency of gastric motility in rats were dose-dependently increased significantly (P < 0.05). SB-334867 microinject to the nucleus accumbens could block the effect on gastric contraction (P < 0.05). The amplitude and frequency of gastric motility were significantly enhanced after electrical stimulation of LHA in rats (P < 0.05). The effect on gastric motility included by orexin-A was disappeared or weaken following by SB-334867 microinject to the nucleus accumbens (P < 0.05). Conclusions: There exist the neural pathways between lateral nucleus and nucleus accumbens, it can regulate the gastric motility, and this way maybe mediated by the orexin-A receptor signaling pathway. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the protective effect of orexin-A on the cerebral ischemia reperfusion injury in rats. Methods: The physiological parameters were observed to define time rang by six rats before MCAO and after MCAO 2h, 24 h. Twenty rats were randomly divided into middle cerebral artery occlusion (MCAO) group, vehicle group, orexin-A 50 μg/kg and orexin-A 100 μg/kg group (n=5). Neurological dysfunction scores (NDS) and infarct volume were measured at 24h after ischemia-reperfusion. The other sixty rats were also divided into 4 groups (n=15 each group), the level of glutathione peroxidase (GSH-PX) and maleic diadehyde (MDA) in brain plasm were detected pre-operation and at 6h, 24 h after ischemia-reperfusion (n=5 each time point). Results:① No significant differentce was found in the pyhsiological parameters ofrats before MCAO and at 2h ,24h after MCAO (P>0.05), suggesting that the follow indexes of cerebral protection hadn't been influenced within 24h after MCAO.② Compared with the MCAO group and vehicle group, the NDS (P<0.05) and the percentage of brain infarct were better in the orexin-A 50 and 100 μg/kg group (P<0.05); the concentration of GSH-PX was increased and MDA was decreased in orexin-A 50 and 100 μg/kg group (P<0.05). Conclusion: Orexin-A might play a protective role in the cerebral ischemia reperfusion injury in rats by increasing the concentration of antiperoxidase and decreasing the level of oxygen free radicals. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of the orexin-A on nycterohemeral food intake in rats. Methods: Male wistar rats were randomly assigned to accept a single intracerebroventricul-ar (ICV) injection, continuous ICV injection and perineural injection, dosed in the daytime and dark phase, then measured the food intake of rats during the whole day of various phases and corresponding biochemical indexes. Results: Compared with NS group, inject orexin-A into ICV in the light phase (08:00) dose-dependently increased food intake following the next 4 h in rats (P<0.05). Food consumption of rats was unchanged after a single administered ICV with orexin- A in the early dark times (18:00) (P＞0.05). Compared with NS group, administered orexin-A into ICV in the light times (12:00) increased food consumption following the next 4 h in rats (P<0.05). Continuous administered ICV with orexin-A significantly increased the food intakes during the light phase (P＜0.05), and reduced it during the dark phase (P＜0.05), but total 24 h food intake was moving (P＞ 0.05). The level of the temperature of brown adipose tissue, peripheral blood glucose, plasma leptin and other indexes were not changed after ICV infusion of orexin-A. Conclusions: The regulation of Orexin-A on food intake in rats was circadian rhythm. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of orexin-A microinjected into the paraventricular nucleus of the hypothalamus (PVN) on body weight in rats. Methods: Chronic guide cannulae were implanted into PVN of rats. Orexin-A was microinjected into the brain site. The effect of orexin-A on body weight in rats was detected. Results: The loss of body weight in orexin-A-treated rats was more significantly than their vehicle-injected counterparts (P<0.05）, but they had no difference in food intake (P＞0.05). The rats were more significantly active after intra-PVN orexin microinjection compared to vehicle（P<0.05）. Conclusion: Orexin-A microinjected into the paraventricular nucleus of the hypothalamus (PVN) can induce weight loss in rats through producing negative energy balance via the increase of physical activity. [ABSTRACT FROM AUTHOR]

Objective: To observe the effect and mechanism of intracerebroventricular(icv) injection of Orexin-A on gastric motility in rats. Methods: 50 adult male rats were randomly divided into five groups, namely normal saline(NS), 1 μg, 5 μg, 10 μg and 20 μg group. Two strain gauge transducers were attached on the antrum and duodenum to record circular muscle contractions. Spontaneous gastroduodenal contractions were recorded in freely moving conscious rats. Through icv injection of OXA, observed the changes in the gastrointestinal circular muscle motion wave form and duration in rats. 10 rats were randomly divided into two groups, one group with subcutaneous injection of NS + icv injection of 10 μg OXA, another group with subcutaneous injection of atropine + icv injection of 10 μg OXA, to observe the effects on gastrointestinal motility. Similarly selecting 10 rats were divided into sham group + 10 μg OXA group,vagotomy + 10 μg OXA group, which was used to elucidate the neural pathways of OXA. Then selecting 10 rats, first icv injection of NS then icv injection of OXA antagonist SB334867, observed the effect of endogenous OXA on gastrointestinal motility. Results: OXA(1-20 μg) disrupted the interdigestive phase III-like contractions and induced an irregular postprandial-like motility pattern in the stomach and duodenum. The stimulatory effect of OXA on gastroduodenal postprandial-like motility pattern was abolished by atropine and truncal vagotomy(P<0.05). Central administration(icv) of selective OXA receptor antagonist, SB-334867(16 μg), enhanced gastric spontaneous phase III-like contractions(P<0.05). Conclusion: Central administration of OXA changes GI motor pattern from interdigestive to postprandial via the vagal cholinergic pathways. Endogenous OXA may inhibit in interdigestive GI motility in rats. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the role of the locus coeruleus (LC) in enhanced orexin-A induced spontaneous activities of obesity-resistant rats and its mechanism and further explore whether LC associated with obesity resistance. Methods: Male Sprague-Dawley and selectively bred OR rats were used. A 26-gauge stainless steel cannula was directed towards the LC of rats. Orexin-A and the vehicle was injected through the cannula tract. And then, measured SPA, Indirect Calorimetry, total fat and fat-free mass. Adiposity was expressed by percent body fat. Results: Compared with SD rats, the OR rats had significantly lower body weight, fat and fat-free mass (P<0.05). OR rats showed significantly less adiposity (P<0.05) than SD rats. OR rats spent more time ambulating at 3 month of age and spent more time vertical at 6 months of age. This resulted in OR rats spending significantly more time moving as increase of age (P<0.05). After the injection of orexin-A, SPA of OR rats was higher than SD rats cause ambulating of OR rats significantly more than vertical activities. The OR rats have higher SPA, lower body weight, and yet the same daily energy expenditure as Sprague-Dawley rats which suggests that OR rats expend more energy on activities during the dark period. In OR rats, the two highest doses of orexin-A increased SPA significantly (P ＜0.05 for both doses) and this was dose dependent. In contrast, in Sprague-Dawley rats only the highest dose of orexin-A significantly increased SPA relative to vehicle (P ＜0.05). The two highest doses of orexin-A significantly increased SPA more robustly in OR rats relative to SD rats (250 pmol: P＜0.05; 500 pmol: P＜0.05). Conclusion: Orexin-A infused into the LC stimulated SPA and related to obesity resistance. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of the fourth ventricle injection of orexin-A (OXA) on food-conditioned place preference in rats. Method: 30 SD male rats were randomly divided into three groups: the control group, low-dose group and high-dose group. The fourth ventricle were injected with saline (NS), orexin-A or orexin-A receptor antagonist SB334867, observed changes of sucrose lever presses and breakpoint of rats. Then selecting 15 rats with fourth ventricle injection orexin-A or SB334867 was observed the effects on HF food intake during daily 1-h tests. At last, 30 rats with fourth ventricle injection orexin-A or SB334867, the rats were placed in conditioned place preference box to detect expression of the place preference of rats with HF food. Results: Compared with the control group, after 24 hours of fasting, The sucrose lever presses and breakpoint of rats were significantly increased through fourth ventricle injection of orexin-A (P<0.05). But SB334867 significantly reduced sucrose lever presses and breakpoint (P<0.05). The HF intake of rats was significantly increased with fourth ventricle injection of orexin-A (P<0.05), while SB334867 did not affect the HF intake, however SB334867 would inhibit chow intake (P<0.05). The expression of HF food-conditioned place preference of rats was enhanced through fourth ventricle injection of orexin-A, while SB334867 inhibited this effect(P<0.05). Conclusion: The Fourth ventricle injection of Orexin-A may affect feeding behavior in rats, increase the intake of HF food, and enhance the expression of HF food-conditioned place preference. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether the rats given glucose in the intermittent access model(IAM) can cause hedonic feeding including bingeing, and the influence of nucleus accumbens and lateral hypothalamic(LHA) orexin(ORX)neurons on fructose eating behavior. Methods: The IAM rats were given 4 %, 8 % or 12 % fructose or Saline(NS). And the fructose intake and fructose eating behavior were observed and recorded in the rats. The receptors number(Bmax) and receptor affinity(Kd) of dopamine D1R and D2R were analyzed in the nucleus accumbens shell, nucleus accumbens core and dorsal striatum. The C-Fos neurons immunoreactivity(Fos-IR)were recorded in paraventricular nucleus, amygdala, nucleus accumbens of related nucleus of the long-term and short-term IAM rat. Food intake was observed while administration of OX1 R antagonist SB334867 in the long term IAM rats. Results: The rats given fructose solutions displayed fructose bingeing but unaltered DA D1R or D2R number following long-term exposure to the IAM. Fructose bingeing rats, as compared to chow bingeing controls, exhibited reduced nucleus accumbens neuron activation, as determined by c-Fos-immunoreactivity. Following short-term access to the IAM, rats exhibited bingeing but unchanged Fos-IR. Fructose bingeing and food intake were significantly reduced while OX1 R antagonist SB-334867(30 mg/kg) were administrated for 21 days in the IAM rats.Conclusion: Long-term fructose bingeing can increase the release of Orexin, reduce the nucleus accumbens Orexin neuron activation,enhance the lateral nucleus Orexin neurons activation. [ABSTRACT FROM AUTHOR]

Objective: To investigate the central and peripheral effects of endogenous Orexin-A(OXA) on gastric motility in rats.Methods: Selecting adult Wistar rats for the study, the synthesis of endogenous OXA was induced by fasting. Plasma OXA concentration was measured by radioimmunoassay. Rats were pretreated with OXA receptor antagonist SB-334867 prior to measurement to observe the effect of OXA.Vagotomy was used to observe vagus nerve-mediated effects. Gastric emptying was measured by spectrophotometric methods. One strain gauge transducers were attached on the antrum to record interdigestive gastric motility. Preproorexin(PPO)expression in stomach and hypothalamus were tested by Western blot. Results: After fasting 18 h, the level of plasma OXA and PPO protein expression were significantly increased(P<0.05). The highest level of plasma OXA and PPO protein expression appeared in 36 h fasting groups(P<0.01). Endogenous OXA promoted gastric emptying(P<0.05), inhibited gastric interdigestive motility(P<0.05). As these effects were abolished with injection of SB-334867, but no effect on PPO expression. Vagotomy surgery did not block endogenous OXA-mediated effects(P>0.05). Conclusion: Fasting can induce the synthesis of endogenous OXA. Endogenous OXA can accelerate gastric emptying, but it suppressed interdigestive gastric motility. [ABSTRACT FROM AUTHOR]

Objective: To investigate the orexin-A(OXA) receptor mediated somatostatin agonists ODT8-SST on the regulation of food intake and water intake of rats and OXA promoting feeding mechanism. Methods: In the light period, 40 rats were randomly divided into 8 groups, the lateral ventricle(icv) were injected with different doses of ODT8-SST or normal saline(NS); 56 rats were randomly divided into 8 groups, icv were injected with different doses of OXA receptor(OX1R) antagonist SB-334867 or NS; the food intake and water intake of rat were recorded for 2 hours after the injection. Results: Compared with NS control group, after injecting ODT8-SST(1μg / rat, icv) into ICV, the food intake and water intake of experimental group were significantly increased(P <0.05). Lateral ventricle injection of OXA receptor(OX1R) antagonist SB-334867(16 μg / rat) completely inhibited the increase in food intake and water intake caused by lateral ventricle injection of ODT8-SST; with in contrast, rats were given SST2 antagonist S-406-028 after pretreatment, can prevent the promotion of the role of appetite caused by intracerebroventricular injection of ODT8-SST, but does not affect the lateral ventricle injection OXA(10.7 μg/rat) induced food intake and water intake increased. Conclusions: Intracerebroventricular injection of ODT8-SST can promote feeding and drinking, OX1 R signaling pathway is a part of the neural circuits; orexin-A promotes the ingestion does not depend on the activation of the brain SST2 pathway. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to test whether activation of orexin signal in Tuberomammillary Nucleus(TMN)can facilitate emergence from katemine anesthesia or not. Methods: Adult male SD rats(body weight 230-280 g) were anesthetized by10% chloral hydrate(1 ml/kg, ip) to do the following work. 1Guide cannulas for microinjection to the TMN were embedded. Then the rats were fed in separate cage. Seven days later, rats were randomly divided into three groups. And then orexin-A(100 pmol/0.3 μL),orexin-B(100 pmol/0.3 μL) and and their solvent NS(0.3 μL) were microinjected into TMN respectively to observe the induction time and awakening time in rats. 2 The same operation as step 1, Seven days later, rats were grouped randomly. And then the OX1 R antagonist SB334867(20 μL/0.3 μL), OX2 R antagonist TCS-OX2-29 and their solvent DMSO(0.3 μL) were microinjected into TMN respectively to observe the time of induction and awakening in rats. Results: 1No statistical difference of induction time was found in each group. 2The rats which injected orexin-A(100 pmol/0.3 μL) recovered much faster from ketamine anesthesia(100 mg/kg, ip) than controlled group(injected NS 0.3 μL)(43.17 ±6.31 min vs 51.17 ±4.45 min,P<0.05).There was no significant difference on the emergence from ketamine anesthesia between the rats received orexin-B and controlled rats(50.33 ±3.50 min vs 51.17 ±4.45 min,P>0.05). 3 The injection of OX1 R antagonist SB334867(20 μL/0.3 μL) to TMN could prolong the emergence time from ketamine anesthesia compared to the solvent DMSO(0.3 μL) group(60.83 ±8.84 min vs 49.00 ±5.73 min, P<0.05). The injection of OX2 R antagonist TCS-OX2-29 did not significantly affect the rat emergence time(50.83±4.79 min vs 49.00±5.73 min, P>0.05). Conclusion:Orexin-A Can facilitates emergence awakening from ketamine anesthesia through histaminergic system in TMN. [ABSTRACT FROM AUTHOR]

Ｏｂｊｅｃｔｉｖｅ　Ｔｏ ｉｎｖｅｓｉｔａｇｅ ｔｈｅ ｅｆｆｅｃｔ ｏｆ Ｏｒｅｘｉｎ-Ａ ｏｎ ｔｈｅ ａｐｏｐｔｏｓｉｓ ｏｆ ｒａｔ ｈｉｐｐｏｃａｍｐａｌ ｎｅｒｖｅ ｃｅｌｌｓ ａｎｄ ｔｈｅ ｍｅｃｈａｎｉｓｍ ｏｆ ａｃｔｉｏｎ． Ｍｅｔｈｏｄｓ　Ｔｈｅ ｐｒｉｍａｒｙ ｃｕｌｔｕｒｅｄ ｈｉｐｐｏｃａｍｐａｌ ｎｅｒｖｅ ｃｅｌｌｓ ｆｒｏｍ ３６ Ｗｉｓｔａｒ ｒａｔｓ ｗｅｒｅ ｒａｎｄｏｍｌｙ ｄｉｖｉｄｅｄｉｎ ｔｈｅ ｅｍｐｔｙ ｖｉｒｕｓ ｇｒｏｕｐ，ＰＬＣβ１ ｇｒｏｕｐ ａｎｄ ＰＬＣβ４ ｇｒｏｕｐ ｗｈｉｃｈ ｗｅｒｅ ｒｅｓｐｅｃｔｉｖｅｌｙ ｔｒａｎｓｆｅｃｔｅｄ ｂｙ ｅｍｐｔｙ ｖｅｃｔｏｒｓ，ｌｅｎｔｉｖｉｒｕｓｅｓｗｉｔｈ ＰＬＣβ１ ａｎｄ ｌｅｎｔｉｖｉｒｕｓｅｓ ｗｉｔｈ ＰＬＣβ４ ． Ａｆｔｅｒ ｔｈｅ ｔｒａｎｓｆｅｃｔｉｏｎ，ａｌｌ ｔｈｒｅｅ ｇｒｏｕｐｓ ｗｅｒｅ ｆｕｒｔｈｅｒ ｄｉｖｉｄｅｄ ｉｎｔｏ ｓｕｂｇｒｏｕｐｓ ｔｒｅａｔｅｄ ｗｉｔｈ Ｏｒｅｘｉｎ-Ａ ｒｅｓｐｅｃｔｉｖｅｌｙ ｆｏｒ ８ ｈ． Ｗｅ ｉｎｖｅｓｔｉｇａｔｅｄ ｔｈｅ ｅｘｐｒｅｓｓｉｏｎ ｏｆ ＥＲＫ１／ ２ ｂｙ Ｗｅｓｔｅｒｎ ｂｌｏｔｔｉｎｇ ａｎｄ ａｐｏｐｔｏｓｉｓ ｒａｔｅ ｗａｓ ｍｅａｓｕｒｅｄ ｂｙ ｆｌｏｗ ｃｙｔｏｍｅｔｒｙ ｆｏｒ ｅａｃｈ ｓｕｂｇｒｏｕｐ． Ｒｅｓｕｌｔｓ　Ａｆｔｅｒ ｔｒｅａｔｍｅｎｔ ｏｆ Ｏｒｅｘｉｎ-Ａ，ｔｈｅ ｅｘｐｒｅｓｓｉｏｎ ｏｆ ＥＲＫ１／ ２ ｗａｓ ｉｎｃｒｅａｓｅｄ ａｎｄ ｔｈｅ ａｐｏｐｔｏｓｉｓ ｒａｔｅ ｗａｓ ｄｅｃｒｅａｓｅｄ ｓｉｇｎｉｆｉｃａｎｔｌｙ ｉｎ ｔｈｅ ＰＬＣβ４ ｇｒｏｕｐ ａｎｄ ｅｍｐｔｙ ｖｉｒｕｓ ｇｒｏｕｐ （ａｌｌ Ｐ ＜０． ０５）． Ｈｏｗｅｖｅｒ，ｔｈｅｓｅ ｃｈａｎｇｅｓ ｉｎ ｔｈｅ ＰＬＣβ１ ｇｒｏｕｐ ｗｅｒｅ ｎｏｔ ｏｂｖｉｏｕｓ ａｆｔｅｒ ｔｒｅａｔｍｅｎｔ ｗｉｔｈ Ｏｒｅｘｉｎ-Ａ （ａｌｌ Ｐ ＞０． ０５）． Ｃｏｎｃｌｕｓｉｏｎ　Ｏｒｅｘｉｎ-Ａ ｍａｙ ｄｅｃｒｅａｓｅ ｔｈｅ ａｐｏｐｔｏｓｉｓ ｏｆ ｒａｔ ｈｉｐｐｏｃａｍｐａｌ ｎｅｒｖｅ ｃｅｌｌｓ，ａｎｄ ｔｈｉｓ ｆｕｎｃｔｉｏｎ ｍａｙ ｂｅ ｒｅｌａｔｅｄ ｗｉｔｈ ＯＸ１Ｒ／ ＯＸ２Ｒ-Ｇｑ-ＰＬＣβ１ ｓｉｇｎａｌｉｎｇ ｐａｔｈｗａｙ. [ABSTRACT FROM AUTHOR]

Obejective To explore the correlation of Orexin A and respiratory drive in chronic obstructive pulmonary 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 levels 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 hypercapnia. Orexin A may play a crucial role in regulating respiratory drive in COPD patients. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of orexin-A on the functionality of ionotropic γ-aminobutyric acid (GABA) receptors in spinal cord ventral horn neurons and its mechanisms., Objective: The spinal cord containing the lumbosacral enlargement was isolated from neonatal SD rats (7-12 days old) and sliced. The slices were digested with papain (in 0.18 g/30 mL artificial cerebrospinal fluid) for 40-60 min, and the ventral horn neurons were separated acutely using fire-polished Pasteur pipettes. After the cells adhered to the bottom of Petri dishes, patch-clamp experiments combined with pharmacological methods were performed to test the effects of orexin-A on GABA currents of the neurons treated with SB334867 (a selective OX 1 R antagonist), TCSOX229 (a selective OX 2 R antagonist), Bis-Ⅳ (a PKC inhibitor), PMA (a PKC agonist), Rp-cAMP (a PKA inhibitor), or BAPTA (Ca 2+ chelator)., Objective: The isolated neurons maintained good morphologies with diverse shapes of cell body and long protrusions. Treatment with orexin-A significantly inhibited the amplitude of GABA-induced current ( P < 0.001, n =49) with an inhibition rate of (67.48±12.50)%. SB334867 and TCSOX229, when applied simultaneously, completely abolished the suppressive effect of orexin-A on the GABA currents ( P =0.93, n =6), and their separate use partially relieved the suppressive effect of orexin-A ( P =0.001, n =8; P =0.02, n =8). The application of Bis-Ⅳ also abolished the suppressive effect of orexin-A on GABA currents ( P =0.31, n =5). PMA mimicked the effect of orexin-A in these neurons and significantly inhibited GABA currents with an inhibition rate of (60.79±10.94)%, and the application of orexin-A did not cause further suppression of GABA currents in PMA-treated neurons ( P =0.15, n =6). Orexin-A was still capable of suppressing GABA currents in Rp-cAMP-treated neurons ( P =0.001, n =5). The extracellular Ca 2+ -free solution ( P =0.004, n =8) or the presence of BAPTA ( P =0.04, n =7) did not significantly affect the inhibitory effect of orexin-A on GABA currents., Objective: Orexin-A inhibits GABA currents in the ventral horn neurons of rat spinal cord probably by activating OX 1 R, OX 2 R and Ca 2+ -independent PKC.