1. Protective Effects Of Ghrelin On Cardiac Function In Diabetic Cardiomyopathy Rats 2. Protective Effect Of Emodin On Cardiac Function In Diabetic Cardiomyopathy Rats And Its Mechanism

Research IThe protective effects of ghrelin on cardiac function in experimental diabetic cardiomyopathy rat model.Part ⅠThe effects of ghrelin on cardiac function in experimental diabetic cardiomyopathy rat model.Objective:The aim of this study was to investigate whether ghrelin is able to reduce cardiac dysfunctions in experimental diabetic cardiomyopathy (DCM) rat model.Methods:diabetic cardiomyopathy rat models were induced by low dose of streptozoticin (STZ) combined with high energy intaken on rats. Diabetic rats were intraperitoneally treated with ghrelin for four weeks. Fasting blood glucose (FBG), Triglyceride (TG), Total cholesterol (TC), Low density lipoprotein cholesterol (LDL-C) and High density lipoprotein cholesterol (HDL-C) were measured by blood chemistry analyzer. Left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular posterior wall thickness (LWPWT), interventricular septal diastolic wall thickness (IVSD) were measured by transthoracic echocardiography with synchromous record of lead II electrocardiogram. Left ventricular ejection fraction (LVEF) and fractional shortening (FS) were examined as an indicator of cardiac function. Paraformaldehyde-fixed hearts were embedded in paraffin, and cut into four micrometer sections. A single cardiomyocyte was observed with images captured from hematoxylin and eosin stained section.Results:The diabetic cardiomyopathy rats have higher values of water intake, food intake and urine volume compared with normal rats. Heart weight index was significantly higher with body weight decreased in the DCM group than control group. In the DCM group, FBG, TG, TC, LDL-C levels were significantly increased as compared with the control group. Diabetic cardiomyopathy rats showed lower LVEF and FS than normal rats. Furthermore, we found that Ghrelin-treated groups displayed significantly higher body weight and lower heart weight index. Ghrelin-treated could markedly decrease FBG, TG and TC levels in diabetic rats. Moreover, the Ghrelin-treated group showed a significantly lower LVEDD, LVESD, IVSD and improved cardiac dysfunction in the heart of diabetic rats by increasing LVEF and FS.Conclusions:Our results demonstrated that ghrelin administration could alleviate diabetic cardiopathy.Part ⅡThe mechanisms of ghrelin effect on cardiac function in experimental diabetic cardiomyopathy rat model.Objective:The aim of this study was to investigate the mechanisms of ghrelin on ardiac function in experimental diabetic cardiomyopathy rat model.Methods:diabetic cardiomyopathy rat models was induced by low dose streptozoticin (STZ) combined with high energy intake on rats. Diabetic cardiomyopathy rats were intraperitoneally treated with ghrelin for four weeks. Cardiac fibrotic regulatory factors, including:adiponectin, matrix metallopeptidase (MMP)-2, MMP-8 and MMP-9, and inflammatory regulators including, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α were measured by reverse transcript-polymerase chain reaction (RT-PCR). Phosphorylation of AMPK, AKT and GSK-3β levels were detected by Western-Blot.Results:The RT-PCR analyses revealed that the mRNA expression levels of IL-1β, IL-6 and TNF-α were significantly higher in DCM group compared with the control.The administration of ghrelin markedly reduced the mRNA expression levels of IL-1β, IL-6 and TNF-α. Furthermore, the mRNA expression levels of adiponectin and MMP-2 were significantly decreased and the mRNA expression levels of MMP-8 were significantly increased in DCM group. The administration of ghrelin significantly increased the mRNA levels of adiponectin and MMP-2. Western-Blot analyses revealed that the protein expression levels of p-AMPK, p-AKT and p-GSK-3β were markedly decreased in DCM group compared with control group. Moreover, ghrelin administration could up-regulate cardiac protein levels of p-AMPK, p-AKT and p-GSK-3(3 in the DCM rat hearts,Conclusions:Our results demonstrated that ghrelin administration alleviated diabetic cardiopathy. This protective effect was accompanied by the ability to reduce myocardial fibrosis and cardiac inflammatory, and to promote phosphorylation of AMPK and AKT/GSK-3β in DCM hearts.Research ⅡThe effects of emodin on cardiac function in experimental diabetic cardiomyopathy rat model.Objective:The aim of this study was to investigate whether emodin (Emo) is able to reduce cardiac dysfunctions in experimental diabetic cardiomyopathy (DCM) rat model.Methods:diabetic cardiomyopathy rat models were induced by low dose streptozoticin (STZ) combined with high energy intaken on rats. Diabetic cardiomyopathy rats were intragastric treated with emodin for 16 weeks. Fasting blood glucose (FBG), Triglyceride (TG), Total cholesterol (TC), Low density lipoprotein cholesterol (LDL-C) and High density lipoprotein cholesterol (HDL-C) were measured by blood chemistry analyzer. Left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular posterior wall thickness (LWPWT), interventricular septal diastolic wall thickness (IVSD) were measured by transthoracic echocardiography with synchromous record of lead Ⅱ electrocardiogram. Left ventricular ejection fraction (LVEF) and fractional shortening (FS) were examined as an indicator of cardiac function. Phosphorylation of AKT and GSK-30 levels were detected by Western-Blot.Results:The rats in DCM group,heart weight index was significantly higher with body weight decreased in the DCM group than control group. In the DCM group, FBG, TG, TC, LDL-C levels significantly increased as compared with the control group. Diabetic cardiomyopathy rats showed lower LVEF and FS than normal rats. Furthermore, we found that Emo-treated groups displayed significantly higher body weight and lower heart weight index. Emo-treated could markedly decrease FBG, TG and TC levels in diabetic cardiomyopathy rats. Moreover, the Emo-treated could improve cardiac dysfunction in the heart of diabetic cardiomyopathy rats by increasing left ventricular fractional shortening and ejection fraction. Western-Blot analyses revealed that the protein expression levels of p-AKT and p-GSK-3β were markedly decreased in DCM group compared with control group. Moreover, emodin administration could up-regulate cardiac protein levels of p-AKT and p-GSK-3β in the DCM rats hearts,Conclusions:Our results suggest that Emo may have great therapeutic potential in the treatment of DCM by AKT/GSK-3β signaling pathway.