Neuropeptide Y promotes TGF-β1 production in RAW264.7 cells by activating PI3K pathway via Y1 receptor

Objective To examine the effect of neuropeptide Y （NPY） on TGF-β1 production in RAW264.7 macrophages. Methods Enzyme linked immunosorbent assay （ELISA） was used to detect TGF-β1 production. Cell counting kit 8 （CCK-8） was used to assay the viability of RAW264.7 cells. Western blot was used to detect the phosphorylation of PI3K p85. Results NPY treatment could promote TGF-β1 production and rapid phosphorylation of PI3K p85 in RAW264.7 cells via Y1 receptor. The elevated TGF-β 1 production induced by NPY could be abolished by wortrnannin pretreatment. Conclusion NPY may elicit TGF-β production in RAW264.7 cells via Y1 receptor, and the activated PI3K pathway may account for this effect.

附子理中汤对脾阳虚模型大鼠在体空肠肌活动、leptin和neuropeptide Y的影响

目的探讨附子理中汤改善脾阳虚证腹泻、食少、体重减轻等症状的机制。方法建立脾阳虚模型大鼠,分对照组,模型组,附子理中汤低剂量组、中剂量组、高剂量组5组。采用生物机能实验系统记录在体大鼠空肠肌活动变化,检测血清瘦素(Lp)和神经肽Y(NPY)水平,对数据进行统计分析。结果和对照组相比,模型组慢波频率显著下降(P<0.01),快波出现频率、最大振幅、每丛快波数均增高(P<0.05或P<0.01);纵肌收缩力振幅和环肌收缩力振幅均显著增大(P<0.01),血清Lp水平显著升高(P<0.01),NPY水平显著降低(P<0.01)。和模型组相比,中剂量组慢波频率上升(P<0.05),快波出现频率、最大振幅、每丛快波数均减小(P<0.05或P<0.01),纵肌收缩力振幅减小(P<0.05),血清Lp水平降低(P<0.05),NPY水平升高(P<0.05);高剂量组慢波频率显著上升(P<0.01),快波出现频率、最大振幅、每丛快波数均显著减小(P均<0.01),纵肌收缩力振幅和环肌收缩力振幅均显著减小(P<0.01),血清Lp水平显著降低(P<0.01),NPY水平显著升高(P<0.01)。结论 Lp和NPY对小肠电生理活动有调节作用。附子理中汤通过调节Lp和NPY水平可能是其发挥止泻增重功效的机制之一。

Apoptosis and Lipolysis of White Adipocytes Induced by Neuropeptide Y- Y5 Receptor Antisense Oligodeoxynucleotides

Objective: To investigate the influence of central administration ofneuropeptide Y-Y5 receptor antisense oligodeoxynucleotides (ODNs) on body weight, fat pads of SDrats, and the effects of white adipocytes lipolysis and apoptosis. Methods: Y5 receptor antisense,sense, mismatched ODNs or vehicle was intracerebroventricularly (i. c. v.) injected. Averageadipocyte area was calculated. DNA ladders were measured to evaluate adipocyte apoptosis, and RT-PCRwas used to analyse the expression of Bcl-2 and Bax gene. Results: Central administration of Y5antisense ODNs significantly decreased body weight, and average adipocyte area. DNA fragmentationwas present after electrophoresis at epididymal adipose tissue. The expression of Bcl-2 gene wasdownregulated, while the expression of Bax upregulated. Conclusion: Lipolysis and adipocyteapoptosis may be important mechanisms far 75 antisense therapy.

Efficacy of Antisense Oligodeoxynucleotide of Neuropeptide Y Y5 Receptor on Treating of Hyperleptinemia by Intraventricular Administration in Diet-induced Obese Rats

Objective: To study the efficacy of antisense oligonucleotide of neuropeptide Y (NPY) Y5 receptor on treating hyperleptinemia by intracerebral ventricular administration in diet-induced obese rats.Methods: The obese rats were prepared by feeding a high-nutritive diet for 7 weeks. The lateral ventricle of obese rats was cannulated. Either 10 μl of different neuropeptide Y Y5 receptor oligodeoxynucleotide, including antisense, sense and missense oligodeoxynucleotide (5 g/L) or 10 μl saline was administered into the ventricle through cannula three times per day in every rat. Two days later the rats were slaughtered .The weights of both retroperitoneal and epididymal adipose tissues were measured, and the serum insulin and leptin were detected by radioimmunoassay method and the murine leptin ELISA kit respectively. Results: ①The level of serum was significantly higher in experimental rats than that in normal rats. Similarly, the level of serum insulin and the weights of both retroperitoneal and epididymal adipose tissues were increased in experimental rats. ②After the diet-induced obese rats were intraventricularly administered with NPY Y5 receptor antisense oligodeoxynucleotide, the levels of serum leptin and insulin were significantly decreased and combined with the reduction of weight in retroperitoneal adipose tissue. There was, however, no significant difference in the weight of epidymal adipose tissue between pre-treated and post-treated duration. ③There was significant positive correlation among the level of serum leptin, the level of serum insulin and the weight of retroperritoneal adipose tissue in diet-induced obese rats. Conclusion: Intracerebral ventricular administration of antisense oligodeoxynucleotide of neuropeptide Y Y5 receptor may alleviate hyperleptinemia in diet-induced obese rats and decrease the weight of retroperitoneal adipose tissue and the level of serum insulin.

Associations of Gonadotropin-Releasing Hormone Receptor (GnRHR) and Neuropeptide Y(NPY) Genes’Polymorphisms with Egg-Laying Traits in Wenchang Chicken

Single nucleotide polymorphisms （SNP） of chicken gonadotropin-releasing hormone receptor （GnRHR） and neuropeptide Y （NPY） were selected to identify the genotypes of Wenchang （Chinese indigenous breed） chicken with restricton fragment length polymorphisms. The associations of the SNPs with the total egg production （NE）, average days of continual laying （ADCL）, and number of double-yolked eggs （DYE） traits were analyzed. The frequency of restriction enzyme A/a alleles in the population was for GnRHR 0.69 （Bpu1102 Ⅰ A） and 0.31 （Bpu1102 Ⅰ a） and for NPY 0.46 （Dra Ⅰ B） and 0.54 （Dra Ⅰ b）. Trait data from a total of 120 hens, which were purebred introduced from Hainan Province, China from one generation were recorded. Two significant effects of genes＇ marker were found： for GnRHR and number of eggs （dominant; t= 2.67, df= 116） and NPY and number of eggs （additive; t= 1.97, df= 116）. The current research supports the effects of GnRHR and NPY genes on egg-laying traits of chickens.

Neuropeptide Y and leptin receptor expression in the hypothalamus of rats with chronic immobilization stress

In this study, Sprague-Dawley rats were immobilized to a frame for 3 hours a day for 21 days to establish a model of chronic immobilization stress. The body weight and food intake of rats subjected to chronic immobilization stress were significantly decreased compared with the control group. Dual-labeling immunofluorescence revealed that the expression of leptin receptor and the co-localization coeffient in these leptic receptor neurons in the arcuate nucleus of the hypothalamus were both upregulated, while the number of neuropeptide Y neurons was decreased. Chronic immobilization stress induced high expression of leptin receptor in the arcuate nucleus and suppressed the synthesis and secretion of neuropeptide Y, thereby disrupting the pathways in the arcuate nucleus that regulate feeding behavior, resulting in diminished food intake and reduced body weight.

Effects of acupuncture therapy on plasma neuropeptide Y levels and resuscitation in patients with very early stage acute cerebral infarction A randomized controlled study

BACKGROUND： It is known that acupuncture therapy can decrease plasma neuropeptide Y （NPY） levels in patients with cerebral infarction, but different types of acupuncture therapy used in various stages of cerebral infarction have not been evaluated. OBJECTIVE： To explore the effect of acupuncture therapy on resuscitation （Xingnao Kaiqiao） and plasma NPY levels in patients with very early stage acute cerebral infarction. DESIGN, TIME AND SETTING： This case-controlled study was performed at the Affiliated Hospital of the Medical College of the Chinese People＇s Armed Police Force between September 2004 and October 2005. PARTICIPANTS： Sixty patients with acute cerebral infarction of ≤ 6 hours were used in this study. Patients were randomly divided into an acupuncture therapy group （n = 30） and a routine treatment group （n = 30）. Another 30 healthy subjects were used as the control group. METHODS： The acupuncture therapy of Xingnao Kaiqiao used in the acupuncture therapy group was based on routine western medical treatment and was performed at bilateral Neiguan （PCG） using the twirling, reinforcing-reducing method, Renzhong （DU26） using heavy bird-pecking needling, Sanyinjiao （SPG） using reinforcing and reducing by lifting and thrusting the needle, Jiquan （HT1）, Weizhong （BL40） and Chize （LU5） using reinforcing and reducing by lifting and thrusting the needle. The acupuncture lasted for 14 days. Patients in the routine treatment group underwent routine medical treatment and no intervention was given to subjects in the control group. MAIN OUTCOME MEASURES： A 4 mL venous blood sample was obtained at different time points, i.e., immediately after hospitalization, the next morning, 7 and 14 days after treatment, to measure plasma NPY levels pre- and post-treatment using the radio-immunity method. RESULTS： The plasma NPY levels were significantly higher in both the routine treatment group and the acupuncture therapy group than in the control group pre- and post-treatment （P 〈 0.01）. In particular, the plasma NPY levels in both the acupuncture therapy group and the routine treatment group were increased 7 days post-treatment but decreased from 7-14 days post-treatment. In addition, the plasma NPY levels were significantly lower in the acupuncture therapy group than in the routine treatment group on day 7 and 14 post-treatment （P 〈 0.01）. CONCLUSION： Acupuncture therapy of Xingnao Kaiqiao can decrease plasma NPY levels in patients with very early stage acute cerebral infarction. In addition, the therapeutic effect of acupuncture with a prolonged therapy time is superior to routine treatment.

Influence of Ganoderma lucidum spores on the levels of neuropeptide Y and somatostatin in brains of seizure rats

BACKGROUND： Previous research has revealed that somatostatin can induce epilepsy, and that the levels of neuropeptide Y may increase and become more active in brain areas with epileptic seizures. OBJECTIVE： To observe the effect of Ganoderma luciclum spore powder on the neuropeptide Y and somatostatin content in the cerebral cortex and hippocampal regions of seizure rats induced by pentylenetetrazol （PTZ）. Furthermore, to verify any effect of Ganoderma lucidum spore powder on inhibition of epileptic seizures. DESIGN, TIME AND SETTING： A randomized group animal study was performed in August 2007 in the School of Basic Medical Sciences, Jiamusi University （Jiamusi, Heilongjiang, China）. MATERIALS： Thirty healthy, male, Wistar rats, aged 12 weeks and weighing 180-220 g, were taken as the experimental animals. PTZ （Sigma Company, United States） was used to induce epilepsy. Ganoderma lucidum spores （Leyss, ex Fr variety） were purchased from Jiamusi City Wild Growing Case of the Ganoderma Lucidum （China）. Rabbit anti-somatostatin antibodies and secondary antibodies were purchased from Wuhan Boster Company （China）. Neuropeptide Y radioimmunoassay kit was purchased from Beijing Furui Biotechnology Company （China）. METHODS： Thirty rats were randomly divided into three groups： a control group, an epilepsy model group and a Ganoderma lucidum spore-treated group. Each group contained 10 animals. Rats in the epilepsy model group were treated with intraperitoneal injections of PTZ and gastric perfusion of physiologic saline. In the Ganoderma lucidum spore-treated group, intraperitoneal injection of PTZ and gastric perfusion of Ganoderma lucidum spore powder were administered. The blank control group was only administered with the physiological saline by intraperitoneal injection and gastric perfusion. MAIN OUTCOME MEASURES： Immunohistochemical staining and radioimmunoassay methods were used to observe the changes of somatostatin and neuropeptide Y content in brain tissue of epileptic rats, as well as the morphology of neurons. RESULTS： All 30 rats were involved in the result analysis, without any loss. The number of somatostatin immunoreacted positive cells in the cerebral cortex and hippocampus was significantly increased in the epilepsy model group compared to the blank control group （P 〈 0.01）. The number of somatostatin immunoreacted positive cells in cerebral cortex and hippocampus was significantly decreased in the Ganoderma lucidum spore-treated group compared to the epilepsy model group （P 〈 0.01）. The contents of neuropeptide Y in cerebral cortex and hippocampus were significantly increased in the epilepsy model group compared to the blank control group （P 〈 0.01）. The contents of neuropeptide Y in the cerebral cortex and hippocampus were significantly decreased in the Ganoderma lucidum spore-treated group compared to the epilepsy model group （P 〈 0.05）. The epilepsy seizures in the Ganoderma lucidum spore-treated group were obviously reduced compared to the epilepsy model group. CONCLUSION： Ganoderma lucidum spore powder was able to reduce the somatostatin and neuropeptide Y content in the cerebral cortex and hippocampus effectively, so as to achieve an anti-epileptic function and protect neurons from being damaged.

The Role of β3-adrenergic Receptor Gene in Neuropeptide Y Y5Receptor Antisense Gene Therapy of Diet-induced Obese Rats

Objective: To study the role of β3-adrenergic receptor gene in neuropeptide Y(NPY) Y5 receptor antisense gene therapy of diet-induced obese rats.Methods: The diet-induced obese rats were prepared by feeding a high-nutrition diet. Lateral ventricular was cannulated in obese rats which then received an intraventricular injection of either 5 μg/μl NPY Y5 receptor antisense or 10 μl missense oligodeoxynucleotide or saline of 10 μl respectively in every rat. When the rats were killed, the wet weight of abdominal adipose tissue, the level of serum lipid and lipoprotein were measured. Total RNA from the retroperitoneal adipose tissue was extracted and the level of β3-adrenergic receptor gene mRNA expression was evaluated by RT-PCR.Results: ①The wet weight of abdominal adipose tissue, the levels of serum lipids were greatly higher in diet-induced obese rats than those in normal rats. However, there were much lower β3-adrenergic receptor gene mRNA expression levels in retroperitoneal adipose tissue in diet-induced obese rats as compared with those in normal rats. ②After the diet-induced obese rats were intraventricularly administered with NPY Y5 receptor antisense oligodeoxynucleotide, the levels of β3-adrenergic receptor gene mRNA expression in retroperitoneal adipose tissue of diet-induced obese rats were strikingly up-regulated, whereas the wet weight of abdominal adipose tissue, the levels of serum lipids were markedly reduced.Conclusion: Intraventricular administration of antisense oligodeoxynucleotide to NPY Y5 receptor could significantly reduce the abdominal adipose tissue and the levels of serum lipids in diet-induced obese rats by up-regulating the level of β3-adrenergic receptor gene mRNA expression in retroperitoneal adipose tissue.

Anti-epileptic effects of neuropeptide Y gene transfection into the rat brain

Neuropeptide Y gene transfection into normal rat brain tissue can provide gene overexpression, which can attenuate the severity of kainic acid-induced seizures. In this study, a recombinant adeno-associated virus carrying the neuropeptide Y gene was transfected into brain tissue of rats with kainic acid-induced epilepsy through stereotactic methods. Following these transfections, we verified overexpression of the neuropeptide Y gene in the epileptic brain. Electroencephalograms showed that seizure severity was significantly inhibited and seizure latency was significantly prolonged up to 4 weeks after gene transfection. Moreover, quantitative fluorescent PCR and western blot assays revealed that the mRNA and protein expression of the N-methyI-D-aspartate receptor subunits NR1, NR2A, and NR2B was inhibited in the hippocampus of epileptic rats. These findings indicate that neuropeptide Y may inhibit seizures via down-regulation of the functional expression of N-methyI-D-aspartate receptors.

Metformin inhibits food intake and neuropeptide Y gene expression in the hypothalamus

Metformin may reduce food intake and body weight, but the anorexigenic effects of metformin are still poorly understood. In this study, Sprague-Dawley rats were administered a single intracere- broventricular dose of metformin and compound C, in a broader attempt to investigate the regula- tory effects of metformin on food intake and to explore the possible mechanism. Results showed that central administration of metformin significantly reduced food intake and body weight gain, par- ticularly after 4 hours. A reduction of neuropeptide Y expression and induction of AMP-activated protein kinase phosphorylation in the hypothalamus were also observed 4 hours after metformin administration, which could be reversed by compound C, a commonly-used antagonist of AMP-activated protein kinase. Furthermore, metformin also improved lipid metabolism by reducing plasma low-density lipoprotein. Our findings suggest that under normal physiological conditions, central regulation of appetite by metformin is related to a decrease in neuropeptide Y gene expres- sion, and that the activation of AMP-activated protein kinase may simply be a response to the anorexigenic effect of metformin.

Neuropeptide Y gene transfection inhibits post-epileptic hippocampal synaptic reconstruction

Exogenous neuropeptide Y has antiepileptic effects; however, the underlying mechanism and optimal administration method for neuropeptide Y are still unresolved. Previous studies have used intracerebroventricular injection of neuropeptide Y into animal models of epilepsy. In this study, a recombinant adeno-associated virus expression vector carrying the neuropeptide Y gene was injected into the lateral ventricle of rats, while the ipsilateral hippocampus was injected with kainic acid to establish the epileptic model. After transfection of neuropeptide Y gene, mossy fiber sprouting in the hippocampal CA3 region of epileptic rats was significantly suppressed, hippocampal synaptophysin （p38） mRNA and protein expression were inhibited, and epileptic seizures were reduced. These experimental findings indicate that a recombinant adeno-associated virus expression vector carrying the neuropeptide Y gene reduces mossy fiber sprouting and inhibits abnormal synaptophysin expression, thereby suppressing post-epileptic synaptic reconstruction.

高胆红素血症新生儿血清CKMB NPY及β_(2)-MG的水平变化及临床意义

目的:探讨高胆红素血症新生儿血清肌酸激酶同工酶(CreatineKinase-MB,CKMB)、神经肽Y(Neuropeptide Y,NPY)及β_(2)-微球蛋白(β_(2)-microglobulin,β_(2)-MG)的水平变化及临床意义。方法:选取本院2019年1月至2022年1月收治的高胆红素血症新生儿118例为观察组,根据总胆红素(total bilirubin,STB)分度分为:轻度组58例(220.6μmoL/L<STB≤256.5μmoL/L),中度组42例(256.5μmoL/L<STB≤342μmoL/L),重度组18例(STB>342μmoL/L);另选取同期于本院经皮胆红素测定无黄疸的健康新生儿112例为对照组。比较对照组、观察组CKMB、NPY及β_(2)-MG水平;比较观察组不同STB程度患者CKMB、NPY及β_(2)-MG水平;根据经皮胆红素测定的STB水平分为急性期组及恢复期组,比较急性期及恢复期两组患者CKMB、NPY及β_(2)-MG水平。结果:观察组CKMB、NPY及β_(2)-MG水平均比对照组高(P<0.05)。不同STB程度患者CKMB、NPY、β_(2)-MG水平比较:轻度组<中度组<重度组(P<0.05)。118例高胆红素血症新生儿中,急性期组67例和恢复期组51例,急性期组CKMB、NPY、β_(2)-MG水平均高于恢复期组(P<0.05)。结论:血清CKMB、NPY及β_(2)-MG与高胆红素血症新生儿病情严重程度及预后关系密切,可通过检测上述指标评估患儿病情进展及预后,具有重要临床意义。

奥美拉唑联合双歧杆菌三联活菌片治疗功能性消化不良的疗效及其对患儿血清神经肽Y水平及摄食情况的影响

目的观察奥美拉唑联合双歧杆菌三联活菌片治疗功能性消化不良的疗效,并探讨其对患儿血清神经肽Y(NPY)水平及摄食情况的影响。方法选择2021年1月至2024年1月中山市博爱医院收治的80例功能性消化不良患儿作为研究对象,按随机数表法分为观察组和对照组各40例。对照组患儿采用双歧杆菌三联活菌片治疗,观察组患儿在对照组治疗的基础上联合奥美拉唑肠溶胶囊治疗,两组患儿均持续治疗4周。比较两组患儿治疗4周后的临床疗效、症状(早饱感、餐后饱胀感、上腹部疼痛、上腹部灼烧感)缓解时间,并比较两组患儿治疗前后的血清NPY、膳食多样化评分(DDS)和治疗期间的不良反应发生率。结果治疗后,观察组患儿的临床总有效率为92.50%,明显高于对照组的75.00%,差异有统计学意义(P<0.05);观察组患儿的早饱感、餐后饱胀感、上腹部疼痛及灼烧感的缓解时间分别为(12.83±2.17)d、(13.55±2.61)d、(3.35±0.63)d、(3.20±0.61)d,明显短于对照组的(15.20±2.79)d、(16.47±2.84)d、(3.91±0.65)d、(3.82±0.68)d,差异均有统计学意义(P<0.05);治疗后,观察组患儿的血清NPY水平为(45.02±4.62)ng/L,明显高于对照组的(37.45±4.25)ng/L,DDS评分为(16.20±1.22)分,明显高于对照组的(13.83±1.37)分,差异均有统计学意义(P<0.05);观察组患儿的不良反应发生率为5.00%,略高于对照组的2.50%,但差异无统计学意义(P>0.05)。结论奥美拉唑联合双歧杆菌三联活菌片治疗功能性消化不良患儿的效果明显,可有效调节患儿血清NPY水平,改善摄食情况,具有临床应用价值。

小鼠在慢性不可预知应激条件下的学习认知能力与神经肽Y、皮质醇的相关性

目的 探讨慢性不可预知轻度应激(chronic unpredictable mild stress, CUMS)状态下小鼠的学习认知能力与血清神经肽Y(neuropeptide Y,NPY)、皮质醇等应激因子水平的相关性。方法 将12只C57BL/6小鼠分为对照组和CUMS组,每组各6只。CUMS组小鼠完成30天CUMS造模,对照组小鼠无特殊处理,定期监测两组小鼠的体质量变化。利用Morris水迷宫实验检测两组小鼠水迷宫运动轨迹、潜伏期、第二象限/第四象限路程比值、穿越平台次数。采用酶联免疫吸附试验(enzyme-linked immunosorbent assay, ELISA)法检测两组小鼠血清NPY、皮质醇、α淀粉酶、酪氨酸水平。结果 造模后第9天CUMS组小鼠体质量较对照组降低(P<0.05),性情易暴躁,提示应激措施有效果,造模成功。Morris水迷宫实验第2天,两组小鼠运动轨迹、潜伏期、第二象限/第四象限路程比值、穿越平台次数比较差异无统计学意义(P>0.05);Morris水迷宫实验第6天,两组小鼠运动轨迹、潜伏期、第二象限/第四象限路程比值、穿越平台次数比较差异具有统计学意义(P均<0.05)。与对照组相比,CUMS组小鼠血清NPY、皮质醇水平升高,差异有统计学意义(P均<0.05)。小鼠血清NPY水平与第二象限/第四象限路程比值存在线性关系(y=-0.001x+1.738,R^(2)=0.586,P=0.004),与潜伏期存在线性关系(y=-0.027x+51.130,R^(2)=0.498,P=0.010)。结论 CUMS状态下,小鼠血清NPY水平的升高与学习认知能力的提高有关。

Neuropeptide Y and nestin expression in the hippocampal CA3 region following restrained and inverted stress in rats

Our preliminary study demonstrated that neuropeptide Y （NPY）/nestin-positive cells exhibit a consistent spatial distribution in the hippocampus of normal adult rats. However, following severe acute and chronic stress-induced impaired learning and memory, synchronous decreased expression of nestin and NPY takes place in the hippocampus, and the underlying mechanisms remain unclear. In the present study, acute and chronic stress rat models were established using combined restrained and inverted stress. Results showed that learning and memory significantly decreased in acute and chronic stress rats. In addition, hippocampal cells were damaged, in particular in the acute stress rats, and nestin and NPY expression, as well as the number of NPY/nestin-positive cells in the CA3 region, significantly decreased. Furthermore, mature neurofilament 200-positive neurons were absent in the chronic stress rats. The NPY and cytoskeletal protein system equally contributed to stress-induced early learning and memory deficits as well as sustained cerebral iniurv in the adult hippocampus.

Type-dependent differential expression of neuropeptide Y in chicken hypothalamus (Gallus domesticus)

Neuropeptide Y （NPY） is one of the most important orexigenic agents in central regulation of feeding behavior, body weight and energy homeostasis in domestic chickens. To examine differences in the hypothalamic NPY between layer-type and meat-type of chickens, which are two divergent kinds of the domestic chickens in feeding behavior and body weight, we detected mRNA levels of NPY in hypothalamic infundibular nucleus （IN）, paraventricular nucleus （PVN） and lateral hypothalamic area （LHA） of these two types of chickens using one-step real time RT-PCR. The meat-type chicken had more food daily （about 1.7 folds） and greater body weights （about 1.5 folds） and brain weights than the layer-type chicken at the age of 14 d. In the meat-type of chicken, NPY mRNA levels of the IN and PVN were significantly greater than those of the LHA, and were not significantly different between the lN and PVN. However, in the layer-type of chicken, NPY mRNA levels were significantly greater in the IN than those in the LHA and PVN, and were not significantly different between the PVN and LHA. In all these hypothalamic regions the layer-type of chicken had significantly higher NPY mRNA levels than the meat-type chicken did. These results suggest the expression of NPY in the hypothalamus has a type-dependent pattern in domestic chickens.

Neuropeptide Y protects cerebral cortical neurons by regulating microglial immune function

Neuropeptide Y has been shown to inhibit the immunological activity of reactive microglia in the rat cerebral cortex, to reduce N-methyl-D-aspartate current（INMDA） in cortical neurons, and protect neurons. In this study, after primary cultured microglia from the cerebral cortex of rats were treated with lipopolysaccharide, interleukin-1β and tumor necrosis factor-α levels in the cell culture medium increased, and mRNA expression of these cytokines also increased. After primary cultured cortical neurons were incubated with the lipopolysaccharide-treated microglial conditioned medium, peak INMDA in neurons increased. These effects of lipopolysaccharide were suppressed by neuropeptide Y. After addition of the neuropeptide Y Y1 receptor antagonist BIBP3226, the effects of neuropeptide Y completely disappeared. These results suggest that neuropeptide Y prevents excessive production of interleukin-1β and tumor necrosis factor-α by inhibiting microglial reactivity. This reduces INMDA in rat cortical neurons, preventing excitotoxicity, thereby protecting neurons.

NPY-Y1信号通路调控嗜酸粒细胞性慢性鼻窦炎大鼠鼻黏膜嗜酸粒细胞性炎症的机制研究

目的探究NPY-Y1信号通路调控嗜酸粒细胞性慢性鼻窦炎(eosinophilic chronic rhinosinusitis,ECRS)大鼠鼻黏膜嗜酸粒细胞性炎症的机制。方法72只大鼠按照体重随机分组法分为6组,每组各12只,包括对照组、ECRS组、空载组、神经肽Y(NPY)干扰组、低拮抗剂组和高拮抗剂组。除对照组外,其余5组采用卵清蛋白致敏+细菌毒素法构建ECRS大鼠模型,空载组和NPY干扰组分别尾静脉注射siNC和NPY siRNA质粒进行干预,低拮抗剂组和高拮抗剂组分别腹腔注射20、50μg的BIBO 3304干预。末次刺激结束后处死大鼠,取鼻腔黏膜组织,进行HE染色和嗜酸粒细胞(Eos)计数;RT-PCT法检测鼻黏膜中NPY、IL-4、IL-5、IL-13 mRNA表达情况,Western blot法检测核因子κB p65(NF-κB p65)、NF-κB p50蛋白表达情况,免疫组织化学法检测NPY、NPY1受体(Y1R)表达情况。结果HE染色结果显示,对照组鼻黏膜组织结构完整有序,ECRS组、空载组细胞排列紊乱,出现大量炎性细胞浸润,低拮抗剂组中细胞结构得到改善,炎性细胞浸润减少,相对于低拮抗剂组,NPY干扰组、高拮抗剂组中细胞结构及炎性细胞浸润改善情况更显著。与对照组比较,ECRS组和空载组鼻黏膜Eos计数,NPY、IL-4、IL-5、IL-13 mRNA,NF-κB p65、NF-κB p50蛋白及NPY、Y1R细胞染色相对强度值均明显升高(P均<0.05);与ECRS组和空载组比较,NPY干扰组、低拮抗剂组、高拮抗剂组上述指标均降低,且NPY干扰组和高拮抗剂组低于低拮抗剂组(P均<0.05);ECRS组与空载组、NPY干扰组和高拮抗剂组上述指标比较差异无统计学意义(P均>0.05)。结论ECRS大鼠存在鼻黏膜Eos异常浸润炎症反应,其机制可能与NPY-Y1信号通路通过激活NF-κB信号通路及效应蛋白表达有关。

Leptin transiently antagonizes ghrelin and long-lastingly orexin in regulation of Ca^(2+) signaling in neuropeptide Y neurons of the arcuate nucleus

AIM： To explore the mechanism for interactions of leptin with ghrelin and orexin in the arcuate nucleus （ARC） activating neuropeptide Y （NPY） neurons during physiological regulation of feeding, METHODS： Single neurons from ARC of adult rats with matured feeding function were isolated. [Ca2＋]i was measured to monitore their activities. The time course of leptin effects on ghrelin-induced versus orexin-induced [Ca2＋]i increases in NPY neurons was studied. RESULTS： Administration of ghrelin or orexin-A at 101~ mol/L increased cytosolic Ca2~ concentration （[Ca2＋]~） in NPY neurons isolated from the ARC of adult rats. Upon administration of leptin at 10^-14-10^-12 mol/L, ghrelin-induced [Ca2＋]i increases were initially （〈 10 min） inhibited but later restored, exhibiting a transient pattern of inhibition. In contrast, orexin-induced [Ca2＋]i increases were inhibited by leptin in a long- lasting manner. Furthermore, a prior administration of leptin inhibited orexin action but not ghrelin action to increase ICa 2＋li, CONCLUSION： Leptin counteracted ghrelin effects transiently and orexin effects long-lastingly in NPY neurons. The transient property with which leptin counteracts ghrelin action in NPY neurons may allow the fasting-associated increase in ghrelin levels to activate NPY neurons in the presence of physiological leptin and to stimulate feeding.