| Background:Heart failure is a global health problem that affects human health and quality of life.Although the treatment of heart failure has made great progress,the therapeutic effect is still not satisfactory.Apelin is an active peptide,which is widely distributed in the cardiovascular system.It mainly has three forms consisting of 36,17,and 13 amino acids.It is formed by the decomposition of a pro protein composed of 77 amino acids.Apelin-13 is in these three the active peptide has the strongest activity.Apelin has a biological effect through its receptor APJ,and its expression level changes in some cardiovascular diseases.However,it is not clear whether Apelin-13 is involved in the regulation of heart failure.Purpose:To investigate whether Apelin-13 can improve heart failure,including cardiac function and left ventricular hemodynamic indicators.To explore whether Apelin-13 can improve heart fibrosis in heart failure rats.To explore whether Apelin-13 can improve heart fibrosis and whether it is related to phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt).To explore whether Apelin-13's improvement of cardiac fibrosis is related to oxidative stress.Methods:The experiment is divided into two parts:in vivo and in vitro.In vivo experiments were performed on male Sprague-Dawley(SD)rats of 160-200 g,and left myocardial infarction(MI)induced heart failure(HF)model after ligation of the left descending coronary artery.The Sham group did the same except that the left descending coronary artery was not ligated,while Apelin-13(10 nmol/kg/day)or saline was produced by intraperitoneal injection(1 time per day).So the rats were divided into 4 groups:Sham+Saline group,Sham+Apelin-13 group,MI+Saline group,MI+Apelin-13 group.After 4 weeks,the rats underwent cardiac ultrasonography and left ventricular hemodynamic test.Then,detecting the effect of Apelin-13 on improving heart fibrosis in heart failure rats by masson staining and fibrosis indicators.In vitro experiments were performed on extracted rat primary fibroblasts(CFs).CFs are divided into 4 groups:PBS group,Angiotensin ?(Ang ?)group,Apelin-13 group,Ang ?+Apelin-13 group.To detect the effects of Apelin-13 on improving Ang ?-induced CFs fibrosis and oxidative stress.To detect the effects of PI3K/Akt cell signal.Results:The mRNA expression level of Apelin in the heart of MI rats was significantly higher than in Sham rats.In addition,the level of Apelin receptor APJ mRNA was increased in the heart of MI rats.Cardiac ultrasonography data showed that MI-induced heart failure in rats with left ventricular ejection fraction(EF)and fractional shortening(FS)were significantly reduced,while Apelin-13 treatment enhanced the decreases of EF and FS in rats with MI.The left ventricular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD),left ventricular volumes in systole(LVVs)and left ventricular volumes in diastole(LVVd)were significantly increased in rats with MI.The application of Apelin-13 significantly inhibited the increases of LVESD,LVEDD,LVVs,and LVVd in MI rats.Hemodynamic data showed that maximum of the first derivative of left ventricular pressure(LV+dP/dtmax)and left ventricular systolic pressure(LVSP)of MI rats were decreased,and Apelin-13 significantly improved the decreases of LV+dP/dtmax and LVSP in MI rats.The left ventricular end-diastolic pressure(LVEDP)in MI rats was increased,and Apelin-13 significantly improved the increase of LVEDP in MI rats.Masson staining data showed that MI left ventricular fibrosis level was significantly increased,and treatment with Apelin-13 significantly inhibited the increase of fibrosis level in MI rats.Collagen ?,collagen ? and transforming growth factor-?(TGF-?)mRNA levels in the heart of MI rat were significantly increased,and the application of Apelin-13 significantly inhibited the increases of collagen I,collagen ?,TGF-?mRNA levels in the heart of MI rat.Collagen I,collagen ? and TGF-? protein levels in the heart of MI rat were significantly increased,and the application of Apelin-13 significantly inhibited the increases of collagen I,collagen ?,TGF-? protein levels in the heart of MI rat.Ang ?-treated cardiac fibroblasts(CFs)significantly increased collagen ?,collagen?,TGF-? and ?-smooth muscle actin(?-SMA)mRNA levels,application of Apelin-13 significantly inhibited the increases of the mRNA levels of collagen ?,collagen ?,TGF-? and ?-SMA in CFs induced by Ang ?.Ang ?-treated CFs significantly increased collagen ?,collagen ?,TGF-? and ?-SMA protein levels,application of Apelin-13 significantly inhibited the increases of the protein levels of collagen ?,collagen ?,TGF-? and ?-SMA in CFs induced by Ang ?.The levels of PI3K and p-Akt in CFs treated with Ang ? were significantly increased.The application of Apelin-13 significantly inhibited the increases of ? PI3K and p-Akt levels in CFs induced by Ang ?.Adenovirus-mediated PI3K overexpression can reverse the effects of Apelin-13 on inhibiting the mRNA levels of collagen ?,collagen?,TGF-? and ?-SMA in CFs cells increased by Ang ?.Adenovirus-mediated PI3K overexpression can reverse the effects of Apelin-13 on inhibiting the protein levels of collagen ?,collagen ?,TGF-? and ?-SMA in CFs cells increased by Ang ?.The activity of NADPH oxidase in the heart of MI rats was significantly increased,and the application of Apelin-13 significantly inhibited the activity of NADPH oxidase in the heart of MI rats.The activity of NADPH oxidase in CFs cells treated with Ang ? was significantly increased,and the application of Apelin-13 significantly inhibited the increase of activity of NADPH oxidase in CFs treated with Ang ?.PI3K overexpression can obviously reverse the effect of Apelin-13 on the inhibition of NADPH oxidase activity in CFs treated with Ang ?.The level of superoxide anion in the heart of MI rats was significantly increased,and the application of Apelin-13 significantly inhibited the increase of superoxide anion in the heart of MI rats.the level of superoxide anion in CFs were increased treated with Ang II,and the treatment of Apelin-13 significantly inhibited the increase of the level of superoxide anion in CFs treated with Ang ?.PI3K overexpression can significantly reverse the effect of Apelin-13 on the effects of inhibiting the increase of superoxide anion level in CFs induced by Ang ?.Conclusions:Apelin/APJ system was increased in the heart of heart failure rats.Apelin-13 can improve heart failure rats,including improving the impaired cardiac function and cardiac hemodynamics in MI-induced heart failure rats.The increase of cardiac fibrosis level in MI rats can be improved by Apelin-13.Apelin-13 reduces CFs fibrosis induced by Ang ? by inhibiting PI3K/Akt signaling pathway.Oxidative stress was increased in MI rat heart,which can be inhibited by Apelin-13 treatment. |
PDF Full Text Request