| ObjectiveTo test the effects of atorvastatin on the expression of lysyl oxidase(LOX)in the myocardial tissue of rats with diabetic cardiomyopathy(DCM)and its related mechanisms with an aim to provide a theoretical basis for the clinical application of atorvastatin in the treatment of diabetic cardiomyopathy.Methods40 normal eight-week old male Sprague-Dawley rats were randomly selected from 50 for making rat models of diabetic cardiomyopathy induced by intraperitoneal injection of streptozotocin(STZ)65mg/kg,the remaining 10 rats were set as control group.After the operation,33 rat models were successful and seven rates were dead.Echocardiography was performed at the fourth week,3 samples were randomly selected from 33 rat models and HE staining was used to evaluate the degree of myocardial fibrosis.The remaining 30 rat models were randomly divided into three groups,ten for each group:(1)Group DCM(equal saline);(2)Group treatment(atorvastatin 2mg/kg/d);(3)Group BAPN(BAPN 80 mg/kg/d).All the rat models were killed at the end of week 8.RNA and protein were extracted from myocardial tissue.RT-PCR was adopted to measure the expression of LOX,MMP-2 m RNA in myocardial tissue.Western Blot was adopted to measure the expression of LOX,MMP-2 and P38 protein kinase and phosphorylated P38 protein.The data were expressed by mean ± standard deviation,and SPSS17.0 was used to compare the data between the two groups by using single factor analysis of variance,p<0.05 was statistically significant.Results(1)The cardiac function of DCM rats was significantly impaired,which showed the significant increase of LVEDd and LVESd,the decrease of LVEF and FS.and HE staining showed edema of myocardial cells and myocardial fibers were broken and arranged in disorder.(2)Compared with the control group,the expression of LOX,MMP-2 m RNA in myocardial tissue of rats in the DCM group were significantly increased(p<0.05);Compared with the DCM group,LOX,MMP-2 m RNA were significantly decreased in the treatment group after the intervention for 4 weeks and 8 weeks respectively(p<0.05).However,there was no significant difference between the intervention of 4weeks and 8 weeks.Compared with the DCM group,the expression of LOX,MMP-2m RNA from group BAPN were significantly decreased(p<0.05).(3)Compared with the control group,the expression of LOX,MMP-2,phosphorylated P38 were significantly increased in the DCM group(p < 0.05);Compared with DCM group,the expression of LOX,MMP-2,P-P38 in myocardial tissue of the treatment group and the group BAPN,were significantly decreased(p<0.05).There was no significant difference in the expression of P38 protein in each group.Conclusion(1)The expressions of LOX,MMP-2 and P-P38 in the rats with diabetic cardiomyopathy were significantly increased,which suggested that LOX may upgrade the expression of MMP-2 via P38 signaling pathway in diabetic cardiomyopathy.(2)LOX,MMP-2 and P-P38 were significantly decreased in the rats with diabetic cardiomyopathy after atorvastatin treatment,which suggested that atorvastatincan can reverse the expression of LOX in the rats with diabetic cardiomyopathy,and may regulate the expression of MMP-2 via P-P38 signaling pathway.This might be an important mechanism of atorvastatin inhibiting myocardial fibrosis. |
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