干细胞移植联合血管内皮生长因子对门静脉高压症大鼠腹膜后交通支形成的影响

背景：研究表明新生血管生成需要内皮细胞和血管生长因子的共同参与。骨髓单个核细胞中的CD34细胞在缺血组织中能分泌多种血管生长因子，可促进新生血管生成。 目的：观察骨髓单个核细胞移植联合血管内皮生长因子能否促进门静脉高压症大鼠腹膜后交通支循环的形成。 设计、时间及地点：随机区组，动物对照观察，于2007-01/04在河南省动物实验中心完成。 材料：清洁级雄性SD大鼠57只，10只用于分离制备骨髓单个核细胞，剩余47只随机分为5组：正常组7只、模型对照组10只、干细胞移植组10只、血管内皮生长因子组10只、联合组10只。血管内皮生长因子为美国Peprotech 公司产品。 方法：除正常组外，其余4组大鼠均建立肝前性门脉高压模型。模型对照组在结扎点以下左侧靠近脊柱的后腹膜沿下腔静脉选取5个注射点，每点注射0.1 mL生理盐水，逐层关腹，常规培养3个月；干细胞移植组每点注射等量骨髓单个核细胞悬液；血管内皮生长因子组每点注射等量稀释后的血管内皮生长因子；联合组每点注射等量骨髓单个核细胞悬液，并紧靠注射点位置注射等量稀释后的血管内皮生长因子。 主要观察指标：门静脉压力及腹膜后交通支造影血流状况。免疫组化技术检测微血管密度。 结果：各组门静脉压力及侧支血管数均基本相似（F=0.313，P > 0.05；F=1.076，P > 0.05）。各组微血管数量比较差异有显著性意义（F=11.756，P < 0.05），微血管密度为联合组>干细胞移植组=血管内皮生长因子组>模型对照组。 结论：异体骨髓干细胞移植及血管内皮生长因子注射均可促进门静脉高压大鼠腹膜后血管的形成，且二者联合可有效缓解门静脉压力。     

心肌梗死大鼠血管生成过程中血管生成素1及其Tie2受体的表达**☆

目的：通过检测正常心肌组织及心肌梗死后血管生成素1及其受体Tie2受体 mRNA的表达水平，探讨其在心肌梗死后的血管新生过程的作用。 方法：实验于2006-04/2007-04在北京大学医学部生物化学与分子生物学基因组实验室完成。将40只雄性SD大鼠随机分为急性心肌梗死组和假手术组，急性心肌梗死组通过结扎前降支建立心肌梗死模型，假手术组只穿线不结扎。于术后3，7，14，28 d 四个时间点，每组取5只处死，取心脏左室前壁同一部位，提取总RNA，用RT-PCR的方法，以GAPDH基因为内参，进行半定量分析检测正常心脏及梗死后血管生成素1及Tie2 mRNA的表达；同时用免疫组化的方法检测各时间点梗死区域以及梗死周边区域血管数量。实验过程中动物处置符合动物伦理学标准。 结果：40只大鼠进入结果分析。血管生成素1及Tie2在正常心肌组织中均有所表达。在心肌梗死后的28 d内，血管生成素1维持在相对不变的水平，而Tie2的表达在心肌梗死后3 d略有升高，于7 d后达顶峰，14 d后恢复正常；急性心肌梗死后7 d, 梗死区及梗死周边区域的血管数量均明显增多，并不随时间的延长而改变，维持在同一水平。 结论：心肌梗死后Tie2受体的表达上调，与血管生成的时间相吻合，提示其在心肌梗死后的血管生成和稳定过程中起了一定的作用。     

血管内皮生长因子在海马伞-穹窿横断后隔区神经干细胞增殖分化中的

背景：目前已经证实成熟脑中存在神经干细胞,如何定向诱导其分化为某种特异性神经元从而替代损伤神经元有效治疗神经系统疾病非常关键。 目的：探讨血管内皮生长因子对体内神经干细胞增殖和分化的作用。 设计、时间及地点：随机对照动物实验,于2007-06/2008-06在中南大学湘雅医学院人体解剖学及神经生物学系完成。 材料：健康雄性SD大鼠24只,随机分为模型对照组、抗体处理组、假手术组,8只/组。 方法：模型对照组、抗体处理组大鼠建立海马伞-穹窿横断模型,假手术组大鼠仅做开颅手术。造模后即刻,抗体处理组吸取抗血管内皮生长因子抗体4 μL,于损伤侧前囟+0.6 mm,外侧+0.6 mm,腹侧-5.5 mm插入进针;模型对照组、假手术组注射等量生理盐水。 主要观察指标：免疫组织化学法观察隔区血管内皮生长因子、巢蛋白、增殖细胞核抗原的表达,计算增殖细胞核抗原增殖指数。 结果：与假手术组比较,模型对照组海马伞-穹窿横断后隔区血管内皮生长因子及巢蛋白的表达强度均明显增高(P < 0.01);与模型对照组比较,抗体处理组巢蛋白表达强度明显降低(P < 0.01)。假手术组增殖细胞核抗原在神经元胞浆内呈弥漫表达,表现为非特异性染色,增殖指数几乎为0;模型对照组出现少量增殖细胞核抗原阳性的神经元,增殖指数为1%;经抗体处理后增殖指数又降为0。 结论：隔区损伤后血管内皮生长因子表达增加的同时确实有神经干细胞的出现。血管内皮生长因子的高表达可能是神经干细胞生成与分化的促进因素,是脑损伤后自我修复的基础。     

血管内皮生长因子在卵巢切除大鼠骨折愈合骨痂中的表达

背景：血管内皮生长因子在骨折愈合过程中起着重要作用,研究发现去卵巢大鼠影响骨折愈合,但其作用机制尚未明确。 目的：观察去卵巢大鼠股骨骨折愈合中骨痂组织学变化以及血管内皮生长因子的表达与分布,探讨骨质疏松对大鼠骨折修复的影响与血管内皮生长因子对其的作用。 方法：取12周龄雌性Sprague-Dawley 大鼠20只,随机分成假手术组和去卵巢组。制造股骨骨折模型,于术后4周处死,各组截取大鼠右侧股骨标本后行计算机X射线摄像仪摄片观察骨折愈合情况,并应用双能X射线骨密度仪测量右股骨骨密度,苏木精-伊红染色观察骨痂生长情况及其组织形态,免疫组织化学染色测定血管内皮生长因子表达。 结果与结论：骨折后4周,去卵巢组形成的骨痂中含有的软骨骨痂比例高与假手术组。去卵巢组中表达血管内皮生长因子的成骨细胞数目少于假手术组。提示骨质疏松大鼠骨折愈合形成的骨痂质量较差,血管内皮生长因子在成骨细胞中的表达减少是骨质疏松骨折愈合质量下降的可能因素之一。 关键词：骨质疏松;骨折愈合;血管内皮生长因子;雌激素;组织构建;组织工程     

一种新的大鼠门静脉动脉化模型*

背景：目前文献报道的大鼠门静脉动脉化模型有缝合法或支架法,2种方法在血管通畅率及操作便利性上均不太理想。 目的：建立稳定的操作简便的大鼠门静脉动脉化动物模型。 方法：采用同种异体血管套入式缝合及袖套法建立大鼠门静脉动脉化模型40例。切除左肾,将左肾动脉与门静脉残端通过同种异体血管连接,左肾静脉借助袖套与肠系膜上静脉连接。另取10只大鼠作为假手术组。术后观察大鼠的体质量变化和存活情况,2周行磁共振血管成像,1个月检测大鼠肝功能,2个月处死大鼠探查门静脉血流通畅情况并观察肝脏的病理学改变。 结果与结论：造模过程中有1只大鼠死亡,其余39只均存活至术后2个月,造模成功率为98%(39/40)。术后1个月,模型组与假手术组大鼠体质量,血清白蛋白、谷丙转氨酶、碱性磷酸酶和胆碱酯酶差异均无显著性意义(P > 0.05)。术后2个月,模型组门静脉通畅率为95%(37/39)。磁共振血管成像及病理结果均未见明显异常。提示,利用同种异体血管套入式缝合及袖套法建立的大鼠门静脉动脉化模型操作简便、省时、成功率高,是一种可行、稳定、可靠、可重复性强的方法。     

大鼠硬脑膜动静脉瘘模型的建立与血管内皮生长因子的表达

目的建立大鼠硬脑膜动静脉瘘(dAVF) 模型;探讨血管内皮生长因子(VEGF)在dAVF形成过程中的作用。方法采用改良Herman方法制作36只Wistar雄性大鼠dAVF模型,将右侧颈总动脉心脏端和颈外静脉头端做端-端吻合,结扎上矢状窦,同时结扎左侧横窦流出静脉。大鼠分为对照组(n= 12);A组VEGF表达组(n= 12),2周后与6只对照组大鼠分别取出硬脑膜做VEGF免疫组织化学染色;B组脑血管造影组(n= 12),90 d后与6只对照组大鼠分别行脑血管造影。结果对照组中极少表达VEGF,脑血管造影无阳性变化;A组7只(58%)大鼠硬脑膜VEGF染色阳性;B组5只(41%)大鼠可见面部、上矢状窦旁或横窦旁发生dAVF。结论在慢性静脉压增高状态下硬脑膜血管中VEGF开始表达,并可能与血管生成及dAVF的发生、发展有重要关系。     

单侧输尿管梗阻模型大鼠肾间质纤维化过程中血小板衍生生长因子D的表达

背景：血小板衍生生长因子在肾间质中通过诱导肾小管间质细胞增生、表型转化、炎性细胞浸润等导致肾小管间质纤维化。 目的：观察血小板衍生生长因子D在单侧输尿管梗阻模型大鼠肾脏组织中的表达水平及随时间的演变情况。 方法：将成年健康雄性SD大鼠60只随机分为模型组及假手术组,将模型组大鼠左侧输尿管结扎剪断建立单侧输尿管梗阻模型,假手术组大鼠不结扎剪断仅游离左侧输尿管。术后3,7,14,21,28 d,通过免疫组化检测血小板衍生生长因子D在肾脏组织中的表达分布情况,实时荧光定量RT-PCR方法检测血小板衍生生长因子D mRNA的表达水平及变化。 结果与结论：假手术组血小板衍生生长因子D仅少量表达于肾小球系膜细胞及血管平滑肌细胞,而在模型组,血小板衍生生长因子D同时表达于肾间质纤维化区域,随纤维化程度加重,表达增多。同时模型组血小板衍生生长因子D mRNA表达量较假手术组显著增多(P < 0.05),且表达随时间延长逐渐增多。提示血小板衍生生长因子D在单侧输尿管梗阻模型肾间质纤维化过程中发挥着促纤维化的重要意义。     

Apelin/APJ信号系统对脑缺血后血管内皮细胞修复及机制的研究

目的 探讨Apelin/APJ信号系统对脑缺血损伤的血管内皮细胞的修复作用.方法 采用电凝烧灼法制备局灶性大脑皮质梗死模型,通过侧脑室注射腺病毒Ad-Apelin或对照病毒Ad-RFP.实验动物随机分为4组,分别为假手术(sham)组、脑梗死组(MCAO)、Ad-Apelin+脑梗死组(Ad-Apelin)组、Ad-R...     

血管生成对慢性低灌注状态下血脑屏障及脑白质损害的影响

目的 了解脑血管生成是否参与脑白质区域慢性低灌注状态下血脑屏障的破坏机制。方法 将72只雄性Wistar大鼠随机分为3组:假手术组、脑缺血组、干预组,脑缺血组及干预组大鼠结扎双侧颈总动脉构建慢性低灌注模型,干预组给予血管生成抑制剂灌胃以抑制血管生成; 对各组大鼠在相同时间点检测脑深部白质区域微血管密度、白质纤维密度以及伊文思蓝静脉注射6 h后脑白质区域组织内伊文思蓝水平。结果 脑缺血组及干预组大鼠脑白质区域血管密度和伊文思蓝浓度均显著高于假手术组,白质纤维密度显著低于假手术组,干预组微血管密度、白质纤维密度及脑组织内伊文思蓝水平显著低于脑缺血组。结论 慢性低灌注诱导的血管生成可能导致血脑屏障通透性增加,但血管生成有助于减轻白质损伤,但这种保护作用大于血脑屏障通透性改变带来的不利影响。     

脑缺血再灌注模型大鼠跑台运动后海马神经再生和血管内皮生长因子mRNA的变化

背景：研究表明跑台运动能促进健康大鼠海马的神经细胞再生。 目的：观察跑台运动对脑缺血再灌注模型大鼠海马神经再生和血管内皮生长因子mRNA表达的影响。 方法：用线栓法阻塞大脑中动脉以建立单侧脑缺血再灌注模型大鼠,将建模成功大鼠随机分为跑台运动组和安静对照组,另设假手术组。安静对照组和假手术组大鼠安静饲养,跑台运动组进行7 d跑台运动。跑台运动组和安静对照组大鼠在每天跑台运动前腹腔注射5-溴脱氧尿嘧啶核苷溶液。 结果与结论：免疫组织化学染色结果显示,跑台运动组大鼠双侧海马及齿状回5-溴脱氧尿嘧啶核苷阳性表达细胞数量显著多于安静对照组(P < 0.01)。实时荧光定量PCR检测结果显示,跑台运动组大鼠海马血管内皮生长因子mRNA表达水平显著高于安静对照组和假手术组(P < 0.05)。结果证实,跑台运动能够明显促进脑缺血再灌注大鼠海马神经细胞的再生并上调海马组织血管内皮生长因子的表达。     

Acute restraint stress induces cholecystokinin release via enteric apelin

Stress increases the apelin content in gut, while exogenous peripheral apelin has been shown to induce cholecystokinin (CCK) release. The present study was designed to elucidate (i) the effect of acute stress on enteric production of apelin and CCK, (ii) the role of APJ receptors in apelin-induced CCK release depending on the nutritional status. CCK levels were assayed in portal vein blood samples obtained from stressed (ARS) and non-stressed (NS) rats previously injected with APJ receptor antagonist F13A or vehicle. Duodenal expressions of apelin, CCK and APJ receptor were detected by immunohistochemistry. ARS increased the CCK release which was abolished by selective APJ receptor antagonist F13A. The stimulatory effect of ARS on CCK production was only observed in rats fed ad-libitum. Apelin and CCK expressions were upregulated by ARS. In addition to the duodenal I cells, APJ receptor was also detected in CCK-producing myenteric neurons. Enteric apelin appears to regulate the stress-induced changes in GI functions through CCK. Therefore, apelin/APJ receptor systems seem to be a therapeutic target for the treatment of stress-related gastrointestinal disorders.     

Diminished Metabolic Responses to Centrally-Administered Apelin-13 in Diet-Induced Obese Rats Fed a High-Fat Diet

The central administration of apelin, a recently identified adipokine, has been shown to affect food and water intake. The present study investigated whether body weight could affect an animal's response to apelin. The effects of centrally-administered apelin-13 on food and water intake, activity and metabolic rate were investigated in adult male diet-induced obese (DIO) rats fed either a high fat (32%) or control diet. Rats were administered i.c.v. apelin-13, 15–30 min prior to lights out, and food and water intake, activity and metabolic rate were assessed. Intracerebroventricular administration of apelin-13 decreased food and water intake and respiratory exchange ratio in DIO rats on the control diet, but had no effect in DIO rats on the high-fat diet. In an effort to identify potential central mechanisms explaining the observed physiological responses, the mRNA level of the apelin receptor, APJ, was examined in the hypothalamus. A high-fat diet induced an up-regulation of the expression of the receptor. Apelin induced a down-regulation of the receptor, but only in the DIO animals on the high-fat diet. In conclusion, we have demonstrated a diminished central nervous system response to apelin that is coincident with obesity.     

Central apelin administration and restraint stress induce hypothalamic cholecystokinin release via the APJ receptor

Exposure to an acute stressor induces up‐regulation of apelin and cholecystokinin (CCK) in the hypothalamic paraventricular nucleus (PVN), which is the key brain centre integrating the stress‐induced alterations in neuroendocrine, autonomic and behavioural functions. We tested the hypothesis that the release of CCK from the PVN is increased by centrally administered or stress‐induced up‐regulated endogenous apelin via the APJ receptor. Additionally, the effect of hypothalamic CCK on autonomic outflow was investigated under basal and stressed conditions. In vivo brain microdialysis was performed in rats that received (i) intra‐PVN administration of apelin‐13 or (ii) acute restraint stress (ARS). For chemical stimulation of the neurones in the PVN, a high concentration of KCl was applied by reverse microdialysis. CCK‐8 levels in microdialysates were quantified by an enzyme immunoassay. The immunoreactivity of the APJ receptor and CCK was detected by immunofluorescence in hypothalamic sections. Heart rate variability was assessed in rats that received PVN stimulation or ARS following pre‐administration of vehicle or CCK1 receptor antagonist lorglumide. Both intra‐PVN exogenous apelin‐13 and ARS increased the CCK‐8 levels in dialysates significantly. The ARS‐induced elevations in CCK levels were reversed by intra‐PVN pre‐administration of the APJ receptor antagonist F13A. Within the PVN, robust APJ receptor expression was detected on the CCK‐producing mediocellular cells, in addition to the parvocellular neurones in the periventricular region. Dual immunoreactivity of APJ/CCK was observed in magnocellular cells to a lesser degree. Both exogenous apelin and ARS increased the CCK immunoreactivity markedly within the PVN, which was diminished significantly by F13A. Sympathetic tonus was increased markedly both by PVN stimulation and ARS, which was attenuated by lorglumide. These results revealed the interaction between apelin and CCK in the brain, suggesting that hypothalamic CCK may contribute to the apelin‐induced alterations in autonomic outflow under stressed conditions.     

Neuroprotective gain of Apelin/APJ system

Apelin is an endogenous ligand of G protein-coupled receptor APJ. In recent years, many studies have shown that the apelin/APJ system has neuroprotective properties, such as anti-inflammatory, anti-oxidative stress, anti-apoptosis, and regulating autophagy, blocking excitatory toxicity. Apelin/APJ system has been proven to play a role in various neurological diseases and may be a promising therapeutic target for nervous system diseases. In this paper, the neuroprotective properties of the apelin/APJ system and its role in neurologic disorders are reviewed. Further understanding of the pathophysiological effect and mechanism of the apelin/APJ system in the nervous system will help develop new therapeutic interventions for various neurological diseases.     

Apelin inhibits motor neuron apoptosis in the anterior horn following acute spinal cord and sciatic nerve injuries

Rat models of acute spinal cord injury and sciatic nerve injury were established.Apelin expression in spinal cord tissue was determined.In normal rat spinal cords,apelin expression was visible;however,2 hours post spinal cord injury,apelin expression peaked.Apelin expression increased 1 day post ligation of the sciatic nerve compared with normal rat spinal cords,and peaked at 3 days.Apelin expression was greater in the posterior horn compared with the anterior horn at each time point when compared with the normal group.The onset of neuronal apoptosis was significantly delayed following injection of apelin protein at the stump of the sciatic nerve,and the number of apoptotic cells after injury was reduced when compared with normal spinal cords.Our results indicate that apelin is expressed in the normal spinal cord and central nervous system after peripheral nerve injury.Apelin protein can reduce motor neuron apoptosis in the spinal cord anterior horn and delay the onset of apoptosis.     

Regulation of rat APJ receptor messenger ribonucleic acid expression in magnocellular neurones of the paraventricular and supraopric nuclei by osmotic stimuli

The novel apelin receptor (APJ receptor, APJR) has a restricted expression in the central nervous system suggestive of an involvement in the regulation of body fluid homeostasis. The endogenous ligand for APJR, apelin, is also highly concentrated in regions that are involved in the control of drinking behaviour. While the physiological roles of APJR and apelin are not fully known, apelin has been shown to stimulate drinking behaviour in rats and to have a regulatory effect on vasopressin release from magnocellular neurones of the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. To determine the role of APJR in the regulation of water balance, this study examined the effects of osmotic stimulation on the expression of APJR mRNA in the magnocellular PVN (mPVN) and SON of salt-loaded and water-deprived rats. Intake of 2% NaCl and water deprivation for 48 h induced expression of APJR mRNA in the mPVN and SON. Using dual-label in situ hybridization histochemistry, we also investigated whether APJR is colocalized within vasopressin neurones in control, salt-loaded and water-deprived rats. APJR mRNA was found to colocalize with a small population of vasopressin-containing magnocellular neurones in control and water-deprived rats. Salt-loading resulted in an increased colocalization of APJR and vasopressin mRNAs in the SON. These data verify a role for APJ receptors in body fluid regulation and suggest a role for apelin in the regulation of vasopressin-containing neurones via a local autocrine/paracrine action of the peptide.     

Chronic central administration of apelin-13 over 10 days increases food intake, body weight, locomotor activity and body temperature in C57BL/6 mice

The peptide apelin has been located in a wide range of tissues, including the gastrointestinal tract, stomach and adipose tissue. Apelin and its receptor has also been detected in the arcuate and paraventricular nuclei of the hypothalamus, which are involved in the control of feeding behaviour and energy expenditure. This distribution suggests apelin may play a role in energy homeostasis, but previous attempts to discern the effects of apelin by acute injection into the brain have yielded conflicting results. We examined the effect of a chronic 10-day intracerebroventricular (i.c.v.) infusion of apelin-13 into the third ventricle on food intake, body temperature and locomotor activity in C57BL/6 mice. Apelin-13 (1 microg/day) increased food intake significantly on days 3-7 of infusion; thereafter, food intake of treated and control individuals converged. This convergence was potentially because of progressive conversion of apelin-13 to [Pyr(1)]apelin-13 which has a four-fold lower receptor binding affinity at the orphan G protein-coupled receptor, APJ. Locomotor activity was also higher in the apelin-treated mice, especially during the nocturnal peak, when most feeding occurs, and the first hours of the light phase. Body temperature was also elevated during this increased period of activity, but was otherwise unaffected. Apelin-13-infused animals gained more weight than the saline-infused controls, suggesting the elevated locomotor activity did not offset the increased food intake. Elevated locomotion and the consequent increases in body temperature were probably secondary effects to the increased food intake. These results suggest that apelin-13 may play a central role in the control of feeding behaviour and is one of only two peripheral ligands known to stimulate rather than inhibit intake. As apelin production is elevated during obesity, this may provide an important feed-forward mechanism exacerbating the problem. Antagonists of the apelin receptor may therefore be useful pharmaceuticals in the treatment of obesity.     

Jacques Benoit lecture: the neuroendocrine view of the angiotensin and apelin systems

The hyperactivity of the brain renin-angiotensin system (RAS) has been implicated in the development and maintenance of hypertension in several types of experimental and genetic hypertension animal models. Among the main bioactive peptides of the brain RAS, angiotensin (Ang) II and Ang III display the same affinity for type 1 and type 2 Ang II receptors. Both peptides, injected intracerebroventricularly, similarly increase arginine vasopressin (AVP) release and blood pressure (BP); however, because Ang II is converted in vivo to Ang III, the identity of the true effector is unknown. We review new insights into the predominant role of brain Ang III in the control of BP, underlining the fact that brain aminopeptidase A (APA), the enzyme generating brain Ang III, may therefore be an interesting candidate target for the treatment of hypertension. This justifies the development of potent systemically active APA inhibitors, such as RB150, as prototypes of a new class of antihypertensive agents for the treatment of certain forms of hypertension. We also searched for a putative angiotensin receptor subtype specific for Ang III and isolated a seven transmembrane-domain G protein-coupled receptor corresponding to the receptor for apelin, a newly-discovered peptide isolated from bovine stomach. Apelin and its receptor are expressed in magnocellular vasopressinergic neurones in the hypothalamus. The central injection of apelin in lactating rats decreases the phasic electrical activity of vasopressinergic neurones and the systemic secretion of AVP, inducing water diuresis. Apelin is therefore a natural inhibitor of the antidiuretic effect of AVP. In addition, systemic administration of apelin decreases BP, improves cardiac contractility and reduces cardiac loading. The development of nonpeptide agonists of the apelin receptor may provide new therapeutic tools for treating water retention, hyponatraemia and cardiovascular diseases. Angiotensins and apelin thus exert opposing but complementary effects, and are thereby determinant for the maintenance of body fluid homeostasis and cardiovascular functions.     

Centrally administered apelin-13 induces depression-like behavior in mice

Apelin, a novel bioactive peptide highly concentrated in the brain, is identified as the endogenous ligand for angiotensin-like 1 receptor (APJ). The present study was designed to investigate the effect of apelin-13 on emotion-related behavior using the forced swimming test (FST) and tail suspension test (TST). Intracerebroventricular (i.c.v.) administration of apelin-13 (0.3, 1 and 3μg/mouse) dose-dependently increased the immobility time in the FST and TST, compared with control group. However, the APJ receptor antagonist apelin-13(F13A) (0.3-10μg/mouse, i.c.v.) had no influence on immobility time in the FST. The increase of immobility time induced by apelin-13 was significantly blocked by apelin-13(F13A), non-selective opioid receptor antagonist naloxone and κ-opioid receptor antagonist nor-binaltorphimine dihydrochloride (nor-BNI), respectively, but not the non-selective corticotrophin-releasing factor (CRF) receptor antagonist α-helical CRF(9-41) in the FST. In order to eliminate the possibility of a false-positive result in the FST or TST, spontaneous activity and motor function were checked. The results demonstrate that apelin-13 alone or antagonists co-administered with apelin-13 did influence spontaneous activity counts. And apelin-13 had no effect on the motor behavior in the rotarod test and wire hanging test. These results indicate that centrally administered apelin-13 elicited depression-like behavior in mice, which was mediated via APJ receptor and κ-opioid receptor, but not CRF receptor.