| Objective To observe the protective effect of carnosine(CAR)on myocardial dysfunction induced by streptozotocin(STZ)in type 2 diabetic rats and to study its possible mechanism.Methods Fifty male Sprague-Dawley(SD)rats were randomly divided into five groups: control group,DCM group,DCM+CAR(100mg.kg-1.d-1),DCM+CAR(300mg.kg-1.d-1),DCM+CAR(900mg.kg-1.d-1).Rats in model group and carnosine-treated group were fed with high-glucose and high-fat diet for four weeks,then injected STZ(40 mg.kg-1)intraperitoneally for one week continuously.The diabetes model was considered successful if the blood glucose was higher than 16.7 mmol/L.After successful modeling,the model group and carnosine administration group continued to be fed with high-glucose and high-fat diet,carnosine treatment group continued to be given carnosine administration,the control group and model group were given the same dose of water gavage.Eight weeks later,blood glucose concentration was measured in caudal vein and cardiac hemodynamics related indexes were measured by physiological recorder.Rats’ body weight,heart weight(HW)and left ventricular weight(LVW)were measured.Heart weight/body weight(HW/BW)and left ventricular weight/body weight(LVW/BW)were calculated.LDH,SOD,MDA activity were measured by kit.Morphological changes of myocardial cells observed by hematoxylin-eosin(HE)staining.The production of reactive oxygen species(ROS)was examined by adopting DHE staining.The apoptotic cells were measured by TUNEL staining.The content of CAR in the myocardium was examined by HPLC.The expressions of BAX,Bcl-2,IκB,p65,TNF-α,IL-6,p38 MAPK,phosphor-p38MAPK(p-p38MAPK),P65 in cytoplasm and nucleuswere measured by Western blot.Results Compared with the control group,STZ administration(1)significantly increased the blood glucose,HW/BW and LVW/BW;(2)decreased the hemodynamic indexes LVSP,±d P/dtmax,and significantly increased LVEDP;(3)the myocardial fibers in myocardial tissue ruptured,and the arrangement of myocardial cells disordered;(4)significantly increased the apoptosis of myocardial cells;(5)enhanced superoxide anion generation(ROS),LDH,MDA content in myocardial tissue,up-regulated the expression of Bax,TNF-α,IL-6,p-p38 MAPK protein,increased the ratio of p-p38 MAPK to p38 MAPK,down-regulated the expression of Bcl-2 protein,increased the expression of p65 protein in nucleus,and decreased the expression of p65 protein in cytoplasm.Compared with DCM group,(1)the blood glucose of rats in CAR group was not significantly improved,but HW/BW and LVW/BW were significantly decreased.(2)The hemodynamic parameters of rats in CAR group were significantly improved,LVSP,+d P/dtmax were significantly increased,and LVEDP was significantly decreased.(3)The abnormal changes of myocardial fibers and myocardial structure were significantly improved in CAR group;(4)The apoptotic rate of myocardial cells was significantly reduced in CAR group;(5)CAR group can reduce LDH,MDA superoxide anion content,increase CAR,SOD content,significantly reduce Bax,TNF-α,IL-6,p-p38 MAPK protein expression,reduce the ratio of p-p38MAPK/p38 MAPK,at the same time increase Bcl-2 protein expression,reduce the expression of p65 protein content in the nucleus,and increase the expression of p65 protein content in the cytoplasm.Conclusion Carnosine can improve myocardial injury and apoptosis and inflammation in diabetic cardiomyopathy rats with type 2 diabetes mellitus.The mechanism may be related to ROS/p38 MAPK signaling pathway. |
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