Apelin改善慢性肾脏病大鼠血管钙化

目的探讨脂肪因子Apelin在慢性肾脏病大鼠血管钙化中的作用。方法将大鼠随机分为对照组(给予正常饮食)、模型组(给予0.75%腺嘌呤饮食复制血管钙化的慢性肾脏病大鼠模型)、 Apelin干预组(给予0.75%腺嘌呤饮食,并用微量泵每天持续注射Apelin-13 20μg/kg)、Apelin处理正常大鼠组(给予正常饮食,并用微量泵每天持续注射Apelin-13 20μg/kg),每组10只。6周后将大鼠处死,用生化法检测血清中肌酐、尿素氮、钙、磷的浓度;ELISA检测血清Apelin-13的浓度;RT-qPCR法检测主动脉中APJ和Pit-1mRNA表达;免疫组化法观察主动脉中Runx2和骨保护素的表达;Von Kossa染色观察主动脉钙盐沉积。结果 6周后,与对照组相比,模型组大鼠血清肌酐及尿素氮水平明显升高(P0.01);血钙降低、血磷升高(P0.01);血清Apelin水平(P0.01)和主动脉中APJ mRNA(P0.05)表达下降;主动脉中Runx2、骨保护素表达增加,明显钙盐沉积,Pit-1 mRNA的表达升高(P0.05)。与模型组相比,Apelin干预组血磷下降(P0.05);血清Apelin水平和主动脉中APJ mRNA表达量均升高(P0.05); Runx2和骨保护素的表达下降,主动脉钙化程度减轻,Pit-1 mRNA表达减少(P0.05)。结论 Apelin可以有效改善慢性肾脏病大鼠血管钙化。     

感染性休克大鼠内源性Apelin及其受体系统表达下调

目的观察内源性Apelin及其受体（血管紧张素受体AT1相关蛋白,APJ）在盲肠结扎和穿孔所致感染性休克大鼠的变化。方法20只雄性Wistar大鼠,体重220～250g,随机分为假手术对照组和晚期休克组。酶联免疫法测定血浆和心肌中Apelin含量,RT-PCR法测定心肌组织Apelin、APJ mRNA水平,Western blot方法测定心肌组织中APJ蛋白水平。结果与假手术组比较,休克组大鼠＋LVdP/dtmax和-LVdP/dtmax明显降低;左心室舒张末期压（LVEDP）增高,平均动脉压降低,心率增快;有严重低血糖症和高乳酸血症。血浆和心肌Apelin含量明显降低（P〈0.01）,心肌组织Apelin、Apelin受体APJ mRNA水平显著下降（P〈0.01）,心肌组织APJ蛋白水平明显降低（P〈0.01）。结论Apelin及其受体系统下调在感染性休克发生发展中可能有重要作用。     

Apelin及其受体和一氧化氮合酶在氧诱导的新生小鼠增生性视网膜病变中表达上调

 目的：通过观察apelin及其受体APJ和一氧化氮合酶（NOS）在氧诱导的新生小鼠增生性视网膜病变中的表达,探讨apelin/APJ和一氧化氮(NO)是否参与了早产儿视网膜病变新生血管的发生。方法：36只7日龄C57BL/6J新生小鼠随机均分为高氧组和对照组。高氧组暴露在75%±2%的氧浓度下5 d后,在正常空气环境下饲养5 d;对照组小鼠在正常氧环境下饲养10 d。两组均在17日龄处死,取左眼眼球做石蜡切片,HE染色计数突破内界膜的血管内皮细胞核数,以判断造模是否成功。实时荧光定量PCR检测右眼视网膜组织apelin和APJ mRNA的表达,免疫荧光组织化学法检测视网膜apelin、APJ、eNOS和iNOS蛋白的表达。结果：高氧组视网膜平均每个切面突破内界膜的血管内皮细胞核数(35.13±10.13)明显高于对照组(0.30±0.21,P<0.01）,说明造模成功。高氧组apelin和APJ mRNA水平显著高于对照组,分别为对照组的32.2倍和17.6倍（均P<0.01）。组织免疫荧光结果显示高氧组apelin和APJ蛋白表达明显强于对照组,并且主要强表达于新生血管周围;高氧组eNOS和iNOS蛋白表达明显强于对照组,但主要强表达于新生血管下方视网膜组织,在突破内界膜的血管内皮细胞核周围未见表达明显增强。结论：Apelin/APJ及NOS可能与氧诱导的新生小鼠增生性视网膜病变新生血管的发生有关。     

Apelin/APJ系统在心血管系统中的作用

Apelin是孤儿受体APJ的天然配体，apelin/APJ系统对心血管系统的作用主要为：可以通过拮抗血管紧张素Ⅱ的作用而舒张血管降低血压；可以作用于心肌引起强烈的正性肌力作用；在心力衰竭早期表达增加而心力衰竭晚期表达降低，因此，推测apelin/APJ系统可能是防止心力衰竭发生的有效的代偿方式。Apelin/APJ系统还可能参与调节胰腺对胰岛素的分泌，并且该系统还可以促进视网膜毛细血管的增生。Apelin/APJ系统在心血管系统的这些作用提示该系统可能在高血压、糖尿病血管病变、心力衰竭中发挥了一定的作用。     

门静脉部分缩窄制作SD大鼠门静脉海绵样变性动物模型

目的采用门静脉部分缩窄法建立SD大鼠门静脉海绵样变性(CTPV)的动物模型,观察成模过程中门静脉压力、门静脉及周围组织的结构变化,为临床及基础研究提供可靠、稳定的模型动物。方法将SD大鼠100只,随机分为2组:假手术组和模型组,每组各50只。模型组用21G口径的钝头针对大鼠门静脉部分缩窄术;假手术组仅对门静脉进行游离探查,不进行缩窄。各组分别在术后1、2、3、4、6w随机取出10只,行门静脉测压、门静脉造影、病理学等观察门静脉及其周围组织侧支循环的形成情况。结果假手术组大鼠术后各时间段均未形成门脉高压,门静脉造影未见有侧支循环形成。模型组术后1w即形成门静脉高压,门静脉造影显示术后第3w,肝门区可见向肝性侧支循环,术后6w,门静脉区形成典型的海绵样变性。结论用21G钝针头行门静脉部分缩窄,可以复制出类似CTPV的大鼠模型。术后3w门静脉压力达到高峰,以后稍有下降并逐渐趋于稳定,在术后3w门静脉已出现向肝性侧支循环,到6w时形成典型的门静脉海绵样变性改变。     

提高血流切应力对老年大鼠后肢侧支血管生长的作用

目的　利用老年大鼠股动脉结扎加股动静脉吻合和单纯股动脉结扎的侧支血管生长模型探讨提高血流切应力对老年大鼠侧支血管生长的作用。 方法　老年SD大鼠（24月龄）30只,分为假手术组,结扎组和吻合组。结扎组大鼠行股动脉结扎手术,吻合组大鼠行股动脉结扎加股动静脉吻合手术。大鼠术后存活1周,每组5只大鼠取后肢带侧支血管的肌肉做冰冻切片用于免疫荧光组织化学法检测eNOS,Ki67和MMP2的表达;另外5只使用明胶四氧化三铅进行血管造影再用X线拍照观察侧支血管的生长情况。 结果　与假手术组相比,结扎组的大鼠后肢侧支血管数量增多（P<0.01）,Ki67阳性细胞数量增多（P<0.01）,eNOS的表达显著增强（P<0.001）,MMP2的表达也有所增强（P<0.05）。吻合组与结扎组相比,大鼠的后肢侧支血管数量进一步增多（P<0.01）,Ki67阳性细胞数量明显增多（P<0.01）,eNOS的表达显著增强（P<0.001）,MMP2的表达也明显增强（P<0.01）。 结论　提高血流切应力能促进老年大鼠缺血后肢侧支血管生长。     

肝门静脉海绵样变性模型大鼠组织抑制因子及基质金属蛋白酶表达 与周围血管新生

背景：目前国内外尚无有效治疗肝门静脉海绵样变性的策略,且其病因的基础研究报道较为鲜见。 目的：拟建立大鼠门静脉海绵样变性模型,检测基质金属蛋白酶2,9,基质金属蛋白酶组织抑制剂1,2在大鼠门静脉及其周围组织的表达及周围血管新生中的作用。 方法：SD大鼠80只随机分为3组。以门静脉部分缩窄法复制门静脉海绵样变性的大鼠模型,以21 G钝针头操作。模型组和假手术组分别设术后2,4,6周3个时间点,对照组即不做任何处理的正常SD大鼠(造影后取材)。各组分别于处理后不同时间点行门静脉造影,免疫组织化学检测血管内皮细胞标记物CD31观察门静脉周围血管变化,并使用实时荧光定量PCR和免疫组织化学法检测大鼠门静脉及其周围组织的基质金属蛋白酶2,9,基质金属蛋白酶组织抑制剂1,2 mRNA的含量和蛋白的表达。 结果与结论：门静脉造影及血管内皮细胞标记物CD31免疫组织化学显示,模型组门静脉周围新生血管明显增多。RT-PCR与免疫组织化学结果分析显示：对照组和假手术组基质金属蛋白酶2 mRNA及蛋白表达均较同期模型组低(P < 0.01,P < 0.05),基质金属蛋白酶9 mRNA及蛋白表达均较同期模型组低。模型组基质金属蛋白酶组织抑制剂1,2各个时间段的表达水平与对照组和假手术组相比差异无显著性意义(P > 0.05);模型组造模后第2周基质金属蛋白酶2/基质金属蛋白酶组织抑制剂2比值明显高于对照组和假手术组同期(P < 0.05)。结果提示,构建的门静脉海绵样变性的模型大鼠死亡率低,成模率高,且比较稳定。基质金属蛋白酶2,9表达升高以及基质金属蛋白酶2/基质金属蛋白酶组织抑制剂2的比值失衡,可能是大鼠门静脉海绵样变周围血管新生的分子机制之一。 中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程全文链接：     

急性心肌梗死模型大鼠经血管内皮生长因子121基因治疗后的血管新生☆

背景：血管内皮生长因子121可能是基因治疗急性心肌梗死的合适目的基因之一。 目的：观察直接心肌注射重组腺病毒人血管内皮生长因子121基因(Ad-hVEGF121)对心肌梗死大鼠心脏结构、功能及新生血管影响。 方法：将78只SD大鼠随机分为假手术组(n=18)、心肌梗死组(n=24)、Ad-hVEGF121组(n=19)和生理盐水组(n=17),后3组大鼠经结扎左冠状动脉前降支,建立急性心肌梗死模型。Ad-hVEGF121组和生理盐水组结扎后10~15 min分别在心肌三点注射Ad-hVEGF12和生理盐水。假手术组只开胸,不结扎左冠状动脉前降支。 结果与结论：注射后2周治疗组行心脏超声检查,发现相比于假手术组,心肌梗死组、Ad-hVEGF121组和生理盐水组大鼠心肌新生毛细血管数量、体质量和左心室质量/体质量明显增加(P < 0.05或P < 0.01),且转染rAd-VEGF基因后心肌组织毛细血管密度显著高于生理盐水组和心肌梗死组。但4组大鼠的梗死面积、心脏结构和功能接近。提示直接心肌注射Ad-VEGF121能明显促进心肌内新血管形成。     

电刺激糖尿病模型大鼠创面的愈合及血管生成

文题释义：糖尿病性难愈创面：是最常见的糖尿病并发症之一,主要由于体内高糖环境和多种生物学因素共同作用导致创面形成,大多难以治愈,以糖尿病足为代表,多数患者面临着截肢风险,其主要机制有晚期糖基化终末产物相关学说、炎性浸润、外周神经功能障碍等。 血管生成：指从已有的毛细血管或毛细血管后静脉发展而形成新的血管,主要包括：激活期血管基底膜降解;血管内皮细胞的激活、增殖、迁移;重建形成新的血管和血管网,是一个涉及多种细胞的多种分子的复杂过程。 背景：糖尿病性创面愈合障碍是糖尿病的常见并发症之一,然其发病机制目前尚未阐明。电刺激疗法是临床治疗创面损伤的常用手段之一,能有效促进损伤皮肤愈合。 目的：探讨电刺激疗法对糖尿病大鼠创面愈合及血管生成的影响及潜在机制。 方法：SPF级雄性SD大鼠42只,随机分为空白对照组和糖尿病模型组。模型组采用一次性尾静脉注射链脲佐菌素(50 mg/kg)联合背部皮肤创伤的方法建立糖尿病性难愈创面大鼠模型,再将造模成功的24只大鼠随机分为模型组和电刺激治疗组;空白对照组为正常大鼠造成背部创面,治疗组予以电刺激治疗21 d,对照组和模型组正常饲养,于治疗第3,7,14,21天分别评价创面愈合情况。治疗完成后,取大鼠血清和创面组织用于指标检测,采用苏木精-伊红染色法观察大鼠创面病理形态,酶联免疫吸附法检测血清内皮型一氧化氮合酶、血管生成素1和血管内皮生长因子水平,免疫组织化学法和Western-blotting法定位定量观察创面血管生成素受体2和血管内皮细胞生长因子受体2蛋白的表达。实验方案经西南医科大学附属医院动物实验伦理委员会批准。结果与结论：①经电刺激治疗后,糖尿病大鼠创面愈合率于第14天时即接近90%,而模型组不到60%,差异有显著性意义(P < 0.01);血清内皮型一氧化氮合酶、血管生成素1和血管内皮生长因子水平较模型组均显著升高(P < 0.05或P < 0.01);②与模型组比较,治疗组创面新生血管多,血管管腔较大,血管周围及创面组织的血管生成素受体2和血管内皮细胞生长因子受体2表达均显著升高(P < 0.05或P < 0.01);③电刺激疗法能明显促进糖尿病大鼠创面愈合及新血管生成,其机制与升高内皮型一氧化氮合酶、血管生成素1和血管内皮生长因子水平,上调血管生成素受体2和血管内皮细胞生长因子受体2水平有关。 ORCID: 0000-0001-9624-6694(耿康) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

老年大鼠后肢高血流剪切力诱导的侧支血管生长及其与血管生成素-1表达的关系

目的:检测老年大鼠后肢高血流剪切力诱导的侧支血管生长情况及其与血管生成素-1(Ang-1)表达的关系。方法:实验组取12只老年健康SD大鼠,左侧行股动静脉单纯分离,右侧行股动静脉吻合术,在1周与4周时间点分别处死6只大鼠,采用血管造影与共聚焦免疫荧光术分别观察侧支血管生长情况及Ang-1在血管处的表达情况,正常组3只大鼠用作正常对照组。结果:正常对照组的侧支血管生长与假手术侧无明显差异,但吻合侧的侧支血管生长明显增加,且4周组吻合侧的血管生长多于1周组。正常对照组的血管Ang-1表达与假手术组无明显差异,仅在血管外膜及部分中膜存在表达;1周组吻合侧的Ang-1不仅在原有表达区域明显表达增加,且在内皮细胞处也有所表达;4周组吻合侧Ang-1在血管各层均明显存在高表达。与假手术侧相比,吻合侧Ang-1表达增加,差异具有统计学意义;4周吻合侧的Ang-1荧光强度较1周吻合侧明显增加,其差异也具有统计学意义。结论:老年大鼠后肢高血流剪切力模型可以诱导侧支血管的生长,且与相应部位血管Ang-1表达的增长呈正相关。     

Apelin/APJ expression in the heart and kidneys of hypertensive rats

Hypertension is an important health problem that is manifested by systemic arterial blood pressure being permanently elevated and leading to serious complications. Hypertension is the basis for coronary heart diseases, heart failure, kidney damage, cerebrovascular diseases. Due to ethical concerns, there is no detailed study of the mechanism, side effects and treatment of hypertension in humans. For this reason, specific studies related to the organ of hypertension are performed in experimental animals. The heart and kidney tissue, which are the most important organs that hypertension has damaged, have formed specific organs of our work.In our experimental study, a total of 35 (hypertensive group: 20, control group: 15) Rattus Norvegicus Wistar albino rats were used. In order to obtain our hypertension model, our experimental animals were given L-NAME together with drinking water for six weeks. After six weeks, the experimental procedures were terminated. Heart and kidney tissues of the hypertensive and control group were obtained. Expression of apelin and apelin receptor (APJ) was demonstrated by immunohistochemical and Western Blot protocols.Hypertrophic cardiac atrium of the hearts of the large cavities, interventricular septum and myocardium to the disintegration, as well as an increase in the diameter of the coronary artery has been observed. In general, kidney tissues of the hypertensive group showed narrowing in cortical renal structures and enlargement in structures in the renal medulla.As a result, in hypertensive cases, there was an increase in expression of Apelin and APJ receptor in heart tissue, and a decrease in expression of Apelin and APJ receptor in kidney tissue. We think that our findings may contribute to experimental or clinical studies related to hypertension and apelin.     

Apelin attenuates UVB-induced edema and inflammation by promoting vessel function

Apelin, the ligand of the G protein-coupled receptor APJ, is involved in the regulation of cardiovascular functions, fluid homeostasis, and vessel formation. Recent reports indicate that apelin secreted from endothelial cells mediates APJ regulation of blood vessel caliber size; however, the function of apelin in lymphatic vessels is unclear. Here we report that APJ was expressed by human lymphatic endothelial cells and that apelin induced migration and cord formation of lymphatic endothelial cells dose-dependently in vitro. Furthermore, permeability assays demonstrated that apelin stabilizes lymphatic endothelial cells. In vivo, transgenic mice harboring apelin under the control of keratin 14 (K14-apelin) exhibited attenuated UVB-induced edema and a decreased number of CD11b-positive macrophages. Moreover, activation of apelin/APJ signaling inhibited UVB-induced enlargement of lymphatic and blood vessels. Finally, K14-apelin mice blocked the hyperpermeability of lymphatic vessels in inflamed skin. These results indicate that apelin plays a functional role in the stabilization of lymphatic vessels in inflamed tissues and that apelin might be a suitable target for prevention of UVB-induced inflammation.     

Role of Apelin/APJ axis in cancer development and progression

Apelin is an endogenous peptide, which is expressed in a vast board of organs such as the brain, placenta, heart, lungs, kidneys, pancreas, testis, prostate and adipose tissues. The apelin receptor, called angiotensin-like-receptor 1 (APJ), is also expressed in the brain, spleen, placenta, heart, liver, intestine, prostate, thymus, testis, ovary, lungs, kidneys, stomach, and adipose tissue. The apelin/APJ axis is involved in a number of physiological and pathological processes. The apelin expression is increased in various kinds of cancer and the apelin/APJ axis plays a key role in the development of tumors through enhancing angiogenesis, metastasis, cell proliferation and also through the development of cancer stem cells and drug resistance. The apelin also stops the apoptosis of cancer cells. The apelin/APJ axis was considered in this review as an attractive therapeutic target for cancer treatment.     

The effects of water immersion and restraint stress on the expressions of apelin,apelin receptor (APJR) and apoptosis rate in the rat heart

Apelin has been identified as an endogenous ligand of the orphan G-protein-coupled apelin receptor (APJR). These receptors are widely expressed in the central nervous system and periphery and play a role in the regulation of fluid and glucose homeostasis, feeding behavior, vessel formation, cell proliferation and immunity. We aimed to investigate whether water immersion and restraint stress have effects on apelin and APJR expression and apoptosis in heart tissue of male Wistar rats. The cardiac tissues were obtained from control, water immersion and restraint stress (WIRS) and apelin antagonist (F13A) + WIRS groups of rats and embedded in paraffin wax. Immunohistochemical staining methods were used to localize apelin, APJR and TUNEL immunopositive cells. H-SCORE was used for semi-quantitative determinations. Apelin protein levels were determined by Western blot in the cardiac tissues and plasma corticosteroid levels were measured by enzyme immunoassay (EIA). Apelin immunolocalization was found especially in endothelial cells and mast cells and faintly in cardiomyocytes, APJR immunostaining was shown in endothelial cells and cardiomyocytes, and TUNEL reaction was observed in endothelial cells and in some fibroblasts. Apelin expression was significantly increased in the WIRS and F13A + WIRS groups compared to the control group. The APJR reaction was similar in all groups. The number of TUNEL-positive cells was significantly higher in the F13A + WIRS group than that of the control group. Our study showed that WIRS for 6 h increased plasma corticosterone levels and cardiac apelin expression in rats. The increased levels of apelin inhibited stress-induced apoptosis in heart. These results may be important for the therapeutic approach to a variety of stress-related heart disease.     

Hemodynamic alterations in cirrhosis and portal hypertension

Portal hypertension (PHT) is associated with hemodynamic changes in intrahepatic, systemic, and portosystemic collateral circulation. Increased intrahepatic resistance and hyperdynamic circulatory alterations with expansion of collateral circulation play a central role in the pathogenesis of PHT. PHT is also characterized by changes in vascular structure, termed vascular remodeling, which is an adaptive response of the vessel wall that occurs in response to chronic changes in the environment such as shear stress. Angiogenesis, the formation of new blood vessels, also occurs with PHT related in particular to the expansion of portosystemic collateral circulation. The complementary processes of vasoreactivity, vascular remodeling, and angiogenesis represent important targets for the treatment of portal hypertension. Systemic and splanchnic vasodilatation can induce hyperdynamic circulation which is related with multi-organ failure such as hepatorenal syndrome and cirrhotic cadiomyopathy.     

G protein-coupled APJ receptor signaling induces focal adhesion formation and cell motility

APJ, a G protein-coupled receptor, has an endogenous ligand called apelin. APJ and apelain are highly expressed in the cardiovascular system from embryo to adulthood. It has been shown that apelin elicited the migration of APJ-expressing cells, but details of the receptor signaling have not been identified. To address the signal transduction molecular mechanisms of the apelin/APJ-induced cell motility, we established human embryonic kidney 293T cells stably expressing the mouse APJ (APJ/293T). APJ/293T cells exhibited a specific [(Glp65, Nle75, Tyr77) [125I]]-Apelin13 binding activity (Kd = 4.45 nM). Apelin induced Akt/PKB phosphorylation in APJ/293T cells, but not in the intact 293T cells (-/293T cells). This APJ-dependent activation of Akt/PKB was significantly inhibited by the pretreatment of pertussis toxin (PTx) and a PI3K inhibitor, LY29004. In addition, apelin enhanced focal adhesion kinase (FAK) phosphorylation and increased focal adhesion formation with staining for F-actin in APJ/293T cells. PTx and LY29004 significantly suppressed these responses to apelin. Moreover, we examined the migration activity by using a scratch-test. Apelin strongly accelerated the cell motility in APJ/293T cells, and this activity was abolished by PTx and LY29004. These results indicated that the apelin/APJ signaling coupled with the PTx-sensitive G-protein activates Akt/PKB and FAK proteins through PI3K.     

The protective effect of apelin against water-immersion and restraint stress-induced gastric damage

The aim of the present study was to investigate the gastroprotective effect of apelin on water-immersion and restraint stress (WIRS)-induced gastric lesions. Male Wistar rats were divided into four groups: control, WIRS, F13A + WIRS and F13A. APJ receptor antagonist F13A was administered to rats to determine the influence of apelin on stress-induced gastric injury. WIRS administered for 6 h resulted in the development of gastric mucosal lesions accompanied by a significant increase in plasma corticosterone. WIRS increased the concentration of 4-hydroxynonenol (4-HNE) + malondialdehyde (MDA) and the expression of apelin and hypoxia inducible factor-1α (HIF-1α) in gastric mucosa. In addition, WIRS reduced the mucosal blood flow and gastric prostaglandin E₂ (PGE₂) concentration. Plasma corticosterone, which was increased due to stress, was significantly decreased in the F13A + WIRS group. Gastric lesions and the 4-HNE + MDA concentration were also higher in the F13A + WIRS compared to the WIRS group. We conclude that apelin has a gastroprotective effect against stress-induced lesions possibly by reducing lipid peroxidation in gastric mucosa.     

The role of apelin in the healing of water-immersion and restraint stress-induced gastric damage

The objective of this study was to explore the role of apelin in the healing of gastric lesions induced by stress. Male Wistar rats were exposed to water immersion and restraint stress (WIRS) for 6 h with or without the apelin receptor antagonist F13A. The rats were killed on the 1st, 3rd, 5th or 10th day after the end of stress induction. Apelin and hypoxia-inducible factor-1α expression was increased on the 1st day after the end of stress exposure and was decreased daily thereafter. However, F13A retarded the healing of gastric lesions by preventing the improvement of mucosal blood flow, prostaglandin E₂ production and vascular endothelial growth factor expression in rats exposed to WIRS. Additionally, F13A increased the gastric 4-hydroxynonenol + malondialdehyde content on the 1st and 3rd days after the end of stress induction but did not affect the change in gastric mucosal nitric oxide levels. In conclusion, apelin may be a regulatory protein involved in the healing mechanism of stress-induced gastric damage.