Predictive value of Apelin-13 on coronary artery lesion in Kawasaki disease / 中华实用儿科临床杂志

Objective:To investigate the relationship between the level of Apelin-13 and coronary artery lesion (CAL) in patients with Kawasaki disease (KD), and assess the predictive value of Apelin-13 for CAL in acute phase of KD.Methods:A total of 240 children with KD treated in Chengdu Women and Children′s Central Hospital from September 2017 to October 2019 were recruited, and were divided into KD with CAL (KD-CAL) group and KD without CAL (KD-NCAL) group.Thirty children with acute upper respiratory infection and 30 healthy children were recruited into the febrile control group and the healthy control group, respectively.Blood routine and serum levels of albumin, C-reactive protein (CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP) and Apelin-13 were mea-sured in KD children prior to intravenous gamma globulin injection and after the diagnosis of children in the febrile control group and physical examination of children in the healthy control group.The clinical data of children in each group were compared, and the risk factors of KD complicated with CAL and the predictive value of Apelin-13 were determined by using receiver operating characteristic (ROC) curve and multiple Logistic regression analysis. Results:Apelin-13 and hemoglobin in children with KD were significantly decreased compared with those in the healthy control group and fever control group (all P<0.001). However, white blood cell(WBC) count, platelet count, CRP and NT-proBNP in KD group were significantly increased compared with those in the healthy control group and fever control group (all P<0.001). Serum albumin in KD children was significantly lower than that in the healthy control group ( P=0.004), and there was no difference when compared with the fever control group ( P=0.485). Apelin-13 and hemoglobin were significantly decreased in KD-CAL group compared with KD-NCAL group ( t=10.102, P<0.001; t=2.034, P=0.043), while NT-proBNP and CRP were significantly increased ( t=5.982, 3.728, all P<0.001). Multiple logistic regression analysis showed that Apelin-13 and NT-proBNP were independent predictors of CAL in KD.The ROC curve analysis showed that the cut-off value of Apelin-13 for predicting CAL was 2.99 μg/L, with an area under the curve (AUC) of 0.869 (95% CI: 0.820-0.909), sensitivity of 77.78% and specificity of 88.67%.While NT-proBNP cutoff value of 822 ng/L yielded sensitivity of 57.78% and specificity of 84.62% for predicting CAL with an AUC of 0.718(95% CI: 0.656-0.774). Conclusions:Apelin-13 plays a protective role in KD complicated with CAL, and could be used to predict CAL in the acute phase of KD.

Elabela promotes differentiation of wharton’s jelly-derived mesenchymal stem cells into cardiomyocyte-like cells / 中国组织工程研究

BACKGROUND: Elabela is a new type of endogenous receptor of APJ discovered in recent years. It is widely distributed in the adult cardiovascular system and has a certain influence on cardiovascular diseases. However, the effect of Elabela on the differentiation of stem cells into cardiomyocytes and the expression of APJ in cardiomyocyte differentiation has not been studied yet. OBJECTIVE: To investigate the effect of Elabela on the differentiation of Wharton’s jelly-derived mesenchymal stem cells into cardiomyocytes. METHODS: The frozen mesenchymal stem cells were resuscitated. 5-Azacytidine was used to induce Wharton’s jelly-derived mesenchymal stem cells to differentiate into cardiomyocytes when the cell confluence reached 80%-90%. After 24 hours, the medium was replaced by low-glucose medium containing Elabela and 10% fetal bovine serum in the experimental group, and by low-glucose medium containing 10% fetal bovine serum in the control group. At 7, 14, 21, and 28 days after induction, cell morphology was observed. The total RNA and total protein of each group were collected. The myocardial specific markers Nkx2.5, cTnT and Connexin 43 mRNA and protein expression levels were detected by real-time fluorescent quantitative PCR and western blot assay. The expression of APJ in the induced cardiomyocytes was detected by real-time fluorescent quantitative PCR and flow cytometry. RESULTS AND CONCLUSION: (1) The expression levels of myocardial specific markers Nkx2.5, cTnT and Connexin 43 mRNA and protein were higher in the experimental group than in the control group in all stages of differentiation, and the expression of APJ was also higher in the experimental group than in the control group. (2) In summary, Elabela plays a certain promoting role in the differentiation of Wharton’s jelly-derived mesenchymal stem cells into oriented cardiomyocytes. Elabela, as another agonist of APJ, can promote the expression of APJ during the induced cell differentiation.

Apelin-13 inhibits hypoxia-induced retinal Müller cell apoptosis by regulating YAP entry into the nucleus / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To analyze the function and mechanism of Apelin-13 in preventing the apoptosis of retinal Müller cells induced by hypoxia.<p>METHODS: In the research, the retinal Müller cells are regarded as research subjects, and the control group, hypoxia group and experiment group are set up. The cells of control group are cultivated in normal environment. The cells of hypoxia group are cultivated in hypoxia environment. The cells of experiment group are cultivated in hypoxia environment and are treated with the Apelin-13(1μmol/L). MTT method is used to monitor the changing of the cell viability, and the crystal violet staining method is adopted to observe the cell morphology. In addition, the immunofluorescence staining method is used to test the expression of GFAP and YAP and the TUNEL staining method is used to monitor the cell apoptosis situation and the apoptosis index is calculated. The protein staining method is used to observe the changing of the expression of p-LATS1, p-YAP, LATS1 and YAP protein. <p>RESULTS:The separated and extracted Müller cells grow on the wall and show elongation, polygon and circular shapes. The cytoplasm is plentiful and the cell nucleus show circular shape. The GFAP expression of the cell is positive. The treatment with 0.1, 1, 10μmol/L Apelin-13 can obviously prevent the Müller cell viability decreasing induced by hypoxia(<i>P</i><0.05 or <i>P</i><0.01). Compared with the control group, the cell apoptosis index of hypoxia group is obviously increased(<i>P</i><0.01). However, compared with the hypoxia group, the cell apoptosis index of experiment group is obviously decreased(<i>P</i><0.01). The p-LATS1 and p-YAP protein expression of the control group and hypoxia group does not have big difference. Compared with hypoxia group, the p-LATS1 and p-YAP protein expression of experiment group is obviously decreased(<i>P</i><0.01). The YAP protein expression of cell nucleus of control group and hypoxia group does not have great difference. Compared with hypoxia group, the cell nucleus expression of YAP cell is gretaly increased(<i>P</i><0.01). <p>CONCLUSION: Apelin-13 can be used to prevent the retinal Müller cells apoptosis caused by the hypoxia, which may be related to the regulation of YAP into the nucleus.

Apelin-13 inhibits hypoxia-induced retinal Müller cell apoptosis by regulating YAP entry into the nucleus / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To analyze the function and mechanism of Apelin-13 in preventing the apoptosis of retinal Müller cells induced by hypoxia.<p>METHODS: In the research, the retinal Müller cells are regarded as research subjects, and the control group, hypoxia group and experiment group are set up. The cells of control group are cultivated in normal environment. The cells of hypoxia group are cultivated in hypoxia environment. The cells of experiment group are cultivated in hypoxia environment and are treated with the Apelin-13(1μmol/L). MTT method is used to monitor the changing of the cell viability, and the crystal violet staining method is adopted to observe the cell morphology. In addition, the immunofluorescence staining method is used to test the expression of GFAP and YAP and the TUNEL staining method is used to monitor the cell apoptosis situation and the apoptosis index is calculated. The protein staining method is used to observe the changing of the expression of p-LATS1, p-YAP, LATS1 and YAP protein. <p>RESULTS:The separated and extracted Müller cells grow on the wall and show elongation, polygon and circular shapes. The cytoplasm is plentiful and the cell nucleus show circular shape. The GFAP expression of the cell is positive. The treatment with 0.1, 1, 10μmol/L Apelin-13 can obviously prevent the Müller cell viability decreasing induced by hypoxia(<i>P</i><0.05 or <i>P</i><0.01). Compared with the control group, the cell apoptosis index of hypoxia group is obviously increased(<i>P</i><0.01). However, compared with the hypoxia group, the cell apoptosis index of experiment group is obviously decreased(<i>P</i><0.01). The p-LATS1 and p-YAP protein expression of the control group and hypoxia group does not have big difference. Compared with hypoxia group, the p-LATS1 and p-YAP protein expression of experiment group is obviously decreased(<i>P</i><0.01). The YAP protein expression of cell nucleus of control group and hypoxia group does not have great difference. Compared with hypoxia group, the cell nucleus expression of YAP cell is gretaly increased(<i>P</i><0.01). <p>CONCLUSION: Apelin-13 can be used to prevent the retinal Müller cells apoptosis caused by the hypoxia, which may be related to the regulation of YAP into the nucleus.

Effects of exercise combined with apelin-13 on cardiac function in the isolated rat heart / Efeitos do exercício combinado com apelina-13 na função cardíaca no coração isolado de ratos / Efectos del ejercicio combinado con apelin-13 en la función cardiaca del corazón de ratones aislados

ABSTRACT Exercise and apelin have been shown to increase cardiac function and elicit tolerance to ischemia/reperfusion (IR) injuries. This study aimed at determining whether the combination of exercise training and apelin pretreatment could integrate the protective effects of each of them in the heart against IR injury. Male rats were divided into four experimental groups: 1: Rats with ischemia/reperfusion (IR), 2: subjected to exercise training for 8 weeks (EX+IR), 3: apelin-13 (10 nmol/kg/day) for 7 days (Apel+IR) in the last week of training, and 4: exercise training plus apelin-13 (EX+Apel+IR). Isolated hearts were perfused using the Langendorff method and subjected to 30 min of regional ischemia followed by 60 min of reperfusion. Treadmill exercise training was conducted for 8 weeks. Hemodynamic parameters were recorded throughout the experiment. Ischemia-induced arrhythmias, myocardial infarct size (IS), creatine kinase-MB (CK-MB) isoenzyme and plasma lactate dehydrogenase (LDH) activity was measured in all animals. Administration of apelin-13 plus exercise increased left ventricular developed pressure (LVDP) at the end of ischemia and reperfusion compared with other groups. After 30 min of ischemia, dP/dtmax was higher in EX+Apel+IR than in Apel+IR and EX+IR groups. During 30 min ischemia, exercise training, apelin-13 and combined treatment produced a significant reduction in the numbers of premature ventricular complexes. A combination of exercise and apelin-13 also reduced infarct size, CK-MB, LDH and severity of arrhythmia. These results suggest that combined therapies with apelin-13 and exercise training may integrate the beneficial effects of each of them alone on cardiac contractility, arrhythmia and limiting of infarct size. Level of evidence I; Therapeutic Studies - Investigating the Results of Treatment.

RESUMO Foi demonstrado que o exercício e a apelina aumentam a função cardíaca e induzem a tolerância à lesões por isquemia/reperfusão (IR). O objetivo do presente estudo foi determinar se a combinação de treinamento físico e pré-tratamento com apelidos poderia integrar os efeitos protetores de cada um deles no coração contra a lesão por IR. Ratos machos foram divididos em quatro grupos experimentais: 1- Ratos com isquemia/ reperfusão (IR), 2- submetidos ao treinamento físico por 8 semanas (EX + IR), 3- apelino-13 (10 nmol / kg / dia) por 7 dias (Apel + IR) na última semana de treinamento, 4- treinamento físico mais apelina-13 (EX + Apel + IR). Corações isolados foram perfundidos pelo método de Langendorff e submetidos à 30 min de isquemia regional, seguida de 60 min de reperfusão. Treino em esteira foi conduzido por 8 semanas. Parâmetros hemodinâmicos foram registrados ao longo do experimento. Arritmias induzidas por isquemia, tamanho do infarto do miocárdio (IS), atividade da isoenzima Creatina Cinase-MB (CK-MB) e lactato desidrogenase plasmática (LDH) foram medidos em todos os animais. A administração de apelin-13 mais exercício aumentou a pressão desenvolvida pelo ventrículo esquerdo (LVDP) no final da isquemia e reperfusão em comparação com outros grupos. Após 30 min de isquemia, dp / dtmax foi maior em EX + Apel + IR do que nos grupos Apel + IR e EX + IR. Durante 30 min isquemia, treinamento físico, apelina-13 e tratamento combinado produziram redução significativa no número de complexos ventriculares prematuros. Combinação de exercício e apelina-13 também reduziu o tamanho do infarto, CK-MB, LDH e gravidade da arritmia. Estes resultados sugerem que terapias combinadas com apelina-13 e treinamento físico podem integrar os efeitos benéficos de cada um deles sozinhos na contratilidade cardíaca, arritmia e limitação do tamanho do infarto. Nível de evidência I; Estudos terapêuticos - Investigação dos resultados do tratamento.

RESUMEN Se ha demostrado que el ejercicio y la apelina aumentan la función cardíaca y provocan tolerancia a las lesiones por isquemia/reperfusión (IR). Los objetivos del presente estudio fueron determinar si la combinación de entrenamiento con ejercicio y pre-tratamiento con apelina podrían integrar los efectos protectores de cada uno de ellos en el corazón frente a la lesión por IR. Los ratones machos se dividieron en cuatro grupos experimentales: 1: ratones con isquemia/reperfusión (IR) 2: sometidos a entrenamiento durante 8 semanas (EX + IR), 3: apelina-13 (10 nmol / kg / día) durante 7 días (Apel + IR) en la última semana de entrenamiento 4: entrenamiento físico más apelina-13 (EX + Apel + IR). Los corazones aislados se perfundieron mediante el método de Langendorff y se sometieron a 30 minutos de isquemia regional, seguidos de 60 minutos de reperfusión. El entrenamiento de la cinta de correr se llevó a cabo durante 8 semanas. Los parámetros hemodinámicos se registraron a lo largo del experimento. Se midieron las arritmias inducidas por isquemia, el tamaño del infarto de miocardio (IS), la isoenzima Creatina Kinase-MB (CK-MB) y las actividades de lactato deshidrogenasa plasmática (LDH) en todos los animales. La administración de ejercicios de apelina-13 plus aumenta la presión desarrollada del ventrículo izquierdo (PDVI) al final de la isquemia y la reperfusión en comparación con otros grupos. Después de 30 min de isquemia, la dp/dt max fue más alta en EX + Apel + IR que en los grupos Apel + IR y EX + IR. Durante la isquemia de 30 minutos, el entrenamiento físico, la apelina-13 y el tratamiento combinado, produjeron una reducción significativa en el número de complejos ventriculares prematuros. La combinación de ejercicio y apelina-13 también redujo el tamaño del infarto, CK-MB, LDH y la gravedad de la arritmia. Estos resultados sugieren que las terapias combinadas con apelina-13 y el entrenamiento físico pueden integrar los efectos beneficiosos de cada uno de ellos solo sobre la contractilidad cardíaca, la arritmia y la limitación del tamaño del infarto. Nivel de Evidencia I; Estudios terapéuticos - Investigación de los resultados del tratamiento.

Change of plasma Apelin level in patients with acute pancreatitis and its clinical significance / 重庆医学

Objective To explore the change of plasma Apelin level in the patients with acute pancreatitis(AP) and its clinical significance.Methods Fifty cases of AP in the hospital from July 2015 to June 2016 were collected as the AP group and divided into the mild AP group(MAP) and severe AP group(SAP).Other contemporaneous 30 healthy volunteers undergoing physical examination were selected as the control group.The differences in Apelin-13,Apelin-36 and C reactive protein(CRP) levels on admission and were APACHE Ⅱ score were compared between the two groups.The correlation between Apelin-13 and Apelin-36 with APACHE Ⅱ score was analyzed.The differences of plasma CRP,Apelin-13 and Apelin-36 levels on 4 d after admission were compared between the MAP group and SAP group.Results Plasma Apelin-36,Apelin-36 and CRP levels and APACHE Ⅱ score on admission in the AP group were significantly higher than that in the control group(P＜0.05),plasma Apelin-13,Apelin-36 and CRP levels and APACHE Ⅱ score in the SAP group were significantly higher than those in the MAP group(P＜0.05),the plasma Apelin-13 and Apelin-36 levels were positively correlated with the APACHE Ⅱ score(P＜0.05);the plasma Apelin-36,Apelin-36 and CRP levelson 4 d after admission in the SAP group were higher than those in the MAP group(P＜0.05).Conclusion Early stage of AP has the changes of plasma Apelin-13 and Apelin-36 levels,which are closely correlated with the severity of disease.

Effect of smoking on endothelium-dependent vascular relaxing function and plasma apelin level / 中华全科医师杂志

Objective To explore the effect of smoking on endothelium-dependent vascular relaxing function and endogenous apelin-13 level.Methods Forty healthy volunteers,including 20 smokers and 20 non-smokers were randomly selected and participated in the study from December 2014 to April 2015.During the study period the smokers were asked to quit smoking for one month and the non-smoking group was given short-term smoking intervention.The changes of vascular endothelial function and plasma apelin13 levels were compared between the smoking group and non-smoking group,and before and after intervention.Results Flow-mediated dilatation (FMD) in smoking group was significantly lower than that in non-smoking group [(5.34 ± 1.83) ％ vs.(8.12 ± 2.62) ％,t =-3.75,P ＜ 0.01].FMD in smoking group was significantly increased after 1 month of quitting smoking [(5.34 ± 1.83) ％ vs.(9.05 ± 2.18) ％,t =-6.66,P ＜ 0.01],FMD in non smoking group was slightly decreased [(8.12 ± 2.62) ％ vs.(7.78 ± 1.96) ％,t =0.90,P =0.38] after short-term smoking.The level of plasma apelin-13 in smoking group was significantly lower than that of non smoking group [(44.22 ± 16.58) pg/ml vs.(70.12 ± 24.35) pg/ml,t =-3.79,P ＜ 0.01].The level of plasma apelin-13 in smoking group was significantly increased after 1 month of smoking cessation intervention [(44.22 ± 16.58) pg/ml vs.(65.32 ± 17.13) pg/ml,t =-4.26,P ＜0.01].In non smoking group,the level of plasma apelin-13 was significantly decreased after short-term smoking [(70.12 ± 24.35) pg/ml vs.(45.83 ± 15.66) pg/ml,t =4.93,P ＜ 0.01].Conclusion Cigarette smoking leads to endothelial dysfunction.Short term occlusion of tobacco may significantly improve endothelial function and increase plasma apelin-13 level,suggesting that apelin-13 may be involved in the occurrence and development of endothelial dysfunction induced by cigarette smoking.

Effects of Apelin-13 on expression levels of glucose and lipid metabolism-related genes in the liver and skeletal muscle of diabetic rats / 中华老年医学杂志

Objective To investigate the effects of exogenous Apelin-13 on the expression of glucose and fatty acid metabolism related genes in the liver and skeletal muscle of diabetic rats.Methods Forty male Wister rats were randomly divided into a control group (n=8) and an experimental group (n=32).In the experimental group,a rat model of type 2 diabetes mellitus was established by a high glucose and high-fat diet and intraperitoneal injection of streptozotocin (STZ).The diabetic rats were randomized into a diabetic model group and an Apelin-13 treatment group with 14 rats in each group.Rats in the Apelin-13 treatment group were intraperitoneally injected with 0.1 μmol· kg· d-1 Apelin-13 for 10 weeks,while the control group and the diabetic model group were injected with an equal volume of 0.9％ NaCl solution for 10 weeks.At the end of the 10 week treatment,fasting blood glucose values in each group were measured.Levels of mRNA expression of glucose-6-phosphate (G-6-P),phosphoenolpyruvate carboxykinase (PEPCK),peroxisome proliferatoractivated receptor alpha (PPAR-α),acy1 CoA synthetase long-chain family member1 (ACSL1),and carnitine palmitoyltransferase1 (CPT1) in the liver and levels of mRNA expression of PPAR-α and glucose transporter type 4 (GLUT4) in skeletal muscle were detected by real-time fluorescence quantitative polymerase chain reaction (PCR).Results Levels of mRNA expression of liver PPAR-α,liver ACSL1,liver CPT1,and GLUT4 in skeletal muscle were lower in the diabetic model group (0.309±0.073,0.508±0.056,0.389±0.118 and 0.289±0.066,respectively) than in the control group (0.971±0.028,0.990±0.015,0.987±0.015 and 0.994±0.009,respectively) (all P＜0.05);In the Apelin 13 treatment group,their mRNA expression levels (0.663±0.085,0.802±0.079,0.752 ±0.097 and 0.509±0.119,respectively) were higher than in the diabetic model group,but lower than in the control group (all P＜0.05).Liver G-6 P and PEPCK mRNA levels in the diabetic model group (1.727±0.05 and 1.309±0.130) were higher than in the control group (1.002±0.005 and 0.993± 0.010) (both P＜0.05),but lower than in the Apelin13 treatment group (2.586±0.208 and 1.842± 0.234) (both P＜0.05).Skeletal muscle PPAR-α mRNA levels in the diabetic model group (0.477± 0.118) and the Apelin-13 treatment group (0.566±0.0780) were lower than in the control group (0.993±0.013) (both P＜0.05),but showed no significant difference between the two experimental groups (P ＞ 0.05).Conclusions Apelin-13 increases the expression of the PPAR,ACSL1,and CPT1 genes in the liver and,to a certain extent,improves fatty acid oxidation metabolism in the liver in type 2 diabetic rats.It also increases the expression of the G-6-P and PEPCK genes,promotes gluconeogenesis in the liver,and may be related to the development of type 2 diabetes.In skeletal muscle,Apelin 13 increases GLUT4 gene expression,moderately improves skeletal muscle metabolism and may play a role in the regulation of oxidative stress.

Research on the promoting role of apelin-13 in proliferation, migration and capillary-like tube formation of RF/6A cells / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effects of apelin-13 on proliferation, migration and capillary-like tube formation of a monkey choroid / retinal endothelial cell line, RF/6A, to clarify whether apelin-13 could promote retinal angiogenesis in vitro.METHODS: RF/6A cells in good conditions were administrated with DMSO (the control group), apelin-13 at 0.1μmol/L (low dose group) or apelin-13 at 1μmol/L (high dose group).Cell proliferation, migration and capillary-like tube formation were detected by using the MTT assay, scratch assay and matrigel assay, respectively, at 24h after plating the cells.RESULTS: Cell proliferation was promoted in both low and high dose apelin-13 groups compared to the control cells (P<0.05);the cell migration distance of both apelin-13 groups was significantly greater than that of the control group (P<0.05);and the number of capillary-like tube structures of both apelin-13 groups was significantly larger than that of the control cells (P<0.05).In addition, cell proliferation, migration and tube formation increased as the concentration of apelin-13 increased.CONCLUSION: Apelin-13 could obviously promote the angiogenesis capacity of RF/6A cells, suggesting that apelin-13 was an important pro-angiogenic factor in retinal endothelial cells.

Effects of apelin-13 on myocardium metabolism in diabetic rats / 中华老年医学杂志

Objectives To investigate the effects of Apelin 13 on myocardial metabolism in diabetic rats.Methods A total of 40 male Wister rats were randomly divided into normal control group (NC,n=8) and experimental group (n =32).Diabetic rats model were induced by high-sugar and high-fat diet combined with low-dose intraperitoneal injection of streptozotocin (STZ).The wellestablished 28 diabetic model rats were randomly divided into diabetic model group (DM,n=14) and apelin-13 treated group (n=14).In the Apelin-13 group,diabetic rats were administered Apelin-13 [0.1 μmol/(kg · d)]by intraperitoneal injection for 10 weeks,while the control group and diabetic model group were given an equal volume of 0.9％ NaCl.At the end of the 10th week,all rats were sacrificed after fasting glucose measurement.Levels of serum free fatty acids (FFA) and myocardial FFA were measured by ELISA.Expression of myocardial glucose transporter member 4 (GLUT4) were detected by immunohistochemistry.The mRNA expressions of myocardial PPARα,CD36 and CPT-1 were detected by real-time fluorescence quantitative PCR.Results Fasting blood glucose,serum FFA and myocardial FFA were significantly higher in DM group than in NC group (all P＜ 0.05).The level of plasma glucose and myocardial FFA were significant lower(P＞0.05) in Apelin-13 treated group than in DM group;but serum FFA was not significantly lower(P＜0.05).The mRNA expressions of PPARα,CD36,CPT-1 in cardiac myocyte were higher in DM group and Apelin-13 treated group than in control(P＜0.05),and lower in Apelin-13 treated group than in DM group(P＜ 0.05).The expression of myocardial GLUT4 was significantly lower in DM group(1.138±0.316)and in Apelin-13-treated group (4.631 ± 1.832) than in NC group(9.132 ± 2.156),(F=65.507,P＜ 0.05),and higher in Apelin-13-treated group than in DM group(P＜0.05).Conclusions Apelin-13 increases myocardial expression of GLUT4,improves utilization of FFA,and it can effectively reduce the expression of PPARα,CD36 and CPT-1.Therefore,it may play a vital role in the improvement of myocardial metabolism in diabetic rats.

Apelin-13 protects the cerebral ischemia-reperfusion injury in rats / 天津医药

Objective To observe the protective effect of Apelin-13 on the cerebral ischemia-reperfusion injury (CIRI), and to explore the possible mechanism in rat model. Methods Fifty male SD rats were randomly divided into five groups:sham group, CIRI model group and Apelin-13 (0.1, 1.0 and 10.0 μg/kg) treatment groups. The model of CIRI was established by filament. After 2 h ischemia, the focal middle cerebral artery was followed by 72 h reperfusion. Apelin-13 was administrated by intracerebroventricular injection 30 minutes before reperfusion. The score of neural function was estimated in different time points. The 2,3,5-triphenyl tetrazolium chloride (TTC) dye was used to calculate the volume and percentage of cerebral infarction. The endoplasmic reticulum stress (ERS) protein markers including glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP) in cerebral cortex were measured by Western blot assay. Results Compared with the sham group, the score of neural function was significantly increased, the infarct rate was reached(47.63 ± 5.81)%and the protein expressions of GRP78 and CHOP were significantly up-regulated in CIRI model group (P＜0.05). There were no significant differences in these data between the CIRI model group and 0.1 μg/kg Apelin-13 treatment group (P＞0.05). Compared with the CIRI group, the neural function defect was significantly improved, the muscle strength was significantly enhanced and the infarct rate was significantly decreased, and the protein expressions of GRP78 and CHOP were significantly down-regulated in the 1.0 and 10.0 μg/kg Apelin-13 treatment groups (P＜0.05). Conclusion Apelin-13 protects the cerebral ischemia-reperfusion injury in rat model, which may be related with the inhibition of endoplasmic reticulum stress.

The effects of Apelin-13 on the behavioral and the expression of YAP in the cerebral ischemia/reperfusion injury of rats / 中华行为医学与脑科学杂志

Objective To investigate the neuroprotective effect of lateral intracerebroventricular injection of Apelin-13 on the YAP expression and the cerebral ischemia/reperfusion (I/R) injury in Wistar rats.Methods Healthy adult male Wistar rats were randomly divided into the sham group, cerebral I/R group and Apelin-13 treatment group.The middle cerebral artery occlusion model was established with ischemia for 1 hour and reperfusion for 24 hours after restricting food and water intake for 12 hours.Apelin-13 was injected into rats' lateral ventricles of Apelin-13 treatment group after reperfusion.Neural function defects was assessed.The volume of infarction was evaluated by TTC staining.The expression levels of YAP were detected by western blot.Results Compared with the cerebral I/R group,the rats in the Apelin-13 treatment group had abetter neurologic score ((2.67±0.33) vs (1.67±0.33) , P＜0.05), the infarction volume was decreased ((30.60± 1.42) ％ vs (23.70± 2.20) ％,P＜0.05) , and YAP expression level was increased in each part of the cerebral tissue(P＜0.05).Conclusion Apelin-13 has a neuroprotective effect,which plays the therapeutic effect by regulating the expression of YAP on cerebral ischemia/ reperfusion (I/R) injury in Wistar rats.

Apelin-13 promote mesenchymal stem cells isolated from Wharton’s jelly to differentiate into vascular networks / 天津医药

Objective To explore the role of apelin-13 in regulating stem cell differentiation into vascular net. Meth?ods Mesenchymal stem cells were isolated from human umbilical Wharton’s jelly using tissue adherence method.Their immunophenotypes were detected by flow cytometry . Passage 3 of WJ-MSCs (Wharton’s jelly-mesenchymal stem cells) were inoculated in 4 flasks, denoted as A1, A2, A3, A4 group. TwentyμL of apelin-13 at concentrations of 0, 1×10-6, 10 × 10-6 and 100 ×10-6 mol/L were added to A1, A2, A3 and A4 respectively each day. After being induced for 7 days, cell mor?phology and viability were observed under inverted microscope. Von Willebrand factor (vWF) was examined by immunofluo?rescence and CD31 was identified by flow cytometry. Upon incubating with three dimensional culture medium of hydrogel, those cultured A1, A2, A3 and A4 were renumbered as S1, S2, S3, S4. Again, twentyμL of apelin-13 at concentrations of 0, 1×10-6, 10 ×10-6and 100 ×10-6 mol/L were used to treat S1, S2, S3 and S4 respectively. After 7 days, cell morphology, via?bility and vas-like networks were observed with inverted microscope. Results Our study showed that WJ-MSCs can be in?duced by apelin 13 to differentiate into endothelial cells lineage indicated by positive of vWF staining. Moreover, CD31 expres?sion increases significantly upon apelin-13 addition in a dosage dependent manner. The endothelial cells line formed vas like networks when cultured with three-dimensional medium containing hydrogel. Conclusion This study demonstrated that ape?lin-13 could promote human umbilical cord-MSCs to differentiate into endothelium lineage then to form vascular networks.

Current Research Progress of Apelin-13 / 天津医药

Apelin is a polypeptide consisting of 77 amino acids. Apelin receptors are found to be the angiotensin-like G protein coupled receptor (APJ). Apelin/APJ system is widely distributed in the peripheral and central nervous system. Apelin-13 is one of the subtypes of Apelin, which has strong biological activity. This study reviewed the new research prog?ress of Apelin-13 on physiological and pathological processes involved in the cardiovascular system, respiratory system, ner?vous system, digestive system and endocrine system.

Effects of Apelin-13 on rat myocardial ischemia-reperfusion injury in vivo and its signal transduction pathway / 上海第二医科大学学报

Objective To investigate the role of apelin-13, a vasoactive peptide, in rat myocardial ischemia-reperfusion injury in vivo and explore its signal transduction pathway. Methods Rats were randomly divided into control group (n=10) and Apelin-13 group (n=15), and in vivo models of rat myocardial ischemia-reperfusion injury were established. Normal saline (control group) or Apelin-13 (Apelin-13 group) was administered intravenously 5 min before reperfusion. TTC and Evan's blue staining were used to determine the infarction size (IS) and area at risk (AAR), apoptotic cells were quantified by TUNEL method, and the expression of ERK1/2 was determined by Western blotting. Results IS/AAR and apoptosis index of Apelin-13 group were significantly lower than those in control group [(38.33±12.95) % vs (52.61±11.00)% and (0.21±0.02) vs (0.31±0.05)](P <0.05). The expression of p-ERK1/2 in Apelin-13 group was significantly increased than that in control group [(1.15±0.16) vs (0.63±0.07)](P < 0.05). Conclusion Apelin-13 may protect rat hearts from in vivo ischemia-reperfusion injury, reduce infarction size and attenuate myocardial apoptosis, which may be mediated by the activation of ERK1/2 MAPK signal transduction pathway.

Apelin-13 microinjection into the paraventricular nucleus aggravates gastric mucosal cellular apoptosis induced by gastric ischemia-reperfusion in rats / 基础医学与临床

Objective To observe effects of Apelin-13 microinjection into the hypothalamic paraventricular nucleus(PVN) on gastric ischemia-reperfusion(GI-R) injury in rats.Methods After Apelin-13 injection into PVN,the experimental model of GI-R was established by clamping the celiac artery for 30 min and then reperfused the artery for 1 h.We used immunohistochemistry to detect the gastric mucosal cells apoptosis,proliferation and the expression of BCL-2,BAX.Results(1)Apelin-13 microinjection into the PVN aggravated GI-R injury in an dose-dependent manner with dosages as 0.2,1.0 or 5.0 ?g,respectively.(2)Compared with GI-R group,Apelin-13 microinjection into PVN markedly increased gastric mucosal cellular apoptosis,decreased the proliferation and promoted protein expression of BAX,but obviously inhibited the protein expression of BCL-2.Conclusion Apelin-13 microinjection into the PVN may aggravate GI-R injury by promoting gastric mucosal cellular apoptosis and inhibiting proliferation.