| Objective: Diabetic cardiomyopathy (DCM) is a special chronic complication of diabetes mellitus (DM). It has a close relation with the high rate of heart failure and death in DM patients.Its major pathological hallmarks were myocardial hypertrophy, focal necrosis, myocardium mesenchyme remod- eling,myocardial fibrosis and so on. RhoA is one member of the Rho protein family and plays an importent role in many cellular basic vital movements.Overexpression of RhoA can induce cardiac hypertrophy,cardiovascular remodeling,ventricular dilatation,the degression of myocardium systolic function and heart failure. However, it needs something to be done about its function during the occurrence and development of cardiomyopathy in DM. Simvastatin is one of cholest- erol-lowering drugs which is prescribed widely and have affirmative therapeutic effect in clinical.Recent studies show that simvastatin has benefical effects on cardiovascular diseases which independent of cholesterol lowering. In this study type 2 diabetes mellitus (T2DM) rat model was copied by giving Sprague-Dawlay (SD) rats high-sugar-fat diet and a low dose of streptozotocin (STZ). Then the protein expression of the RhoA in myocardial tissue of experimental rats were detected in order to discuss the association between the protein expression of RhoA and cardiomyopathy in DM. Furthermore, simvastatin were given to experimental rats to explain its mechanism of protective effects on myocardium.Methods: 10 of 50 SD rats were taken out randomly to be normal control rats (group A) and the rest were taken for test rats. The control rats were fed with general diet while the test rats were fed with high-sugar-fat diet (mixed 20% suger,2.5% cholesterin,15% cooked lard and general diet together). At the end of 6 weeks, the rats whose fasting blood glucose (FBG) was higher than 7.8 mmol/L and insulin sensitivity decreased were considered as T2DM rats. T2DM rats were divided randomly into 2 groups: T2DM model rats (group B), T2DM model rats treated with simvastatin (group C). The experiment lasted 14 weeks. At the end of 6 weeks, body weight, FBG, fasting insulin (FINS) and insulin sensitivity index (ISI) in different group rats were measured. At the end of this experiment, FBG and TG, TC, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C) were detected. Heart weight were measured used for calculating Heart /Body Weight Index(HWI).Myocardium microstructure and ultrastructure of left ventricle were observed with light and electron microscopes. The protein expression of RhoA in myocardium was detected by immunohistochemical staining. The results were analyzed with computer image-analysis system and the integral optical density (IOD) of RhoA was calculated. The data were dealt with SPSS11.0.Results1 Various indexes after 6 weeks: 2 weeks after STZ injection, FBG(12.99±1.16)mmol/L of test rats was higher compared to FBG(5.03±0.69)mmol/L of control rats,FINS 18.79(18.23, 19.29)mIU/L of test rats compared to FINS 18.35(17.95, 18.98)mIU/L of control rats was unstatistics distinction (P>0.05), ISI 0.0048(0.0045, 0.0053) of test rats was lower than ISI 0.0106(0.0103, 0.0112) of control rats (P<0.01). Thus far, the T2DM rat model was accomplished.2 Various biochemical indexes after 14 weeks: When the experiment was finished, There were FBG(4.96±0.92)mmol/L,TG(0.67±0.21)mmol/L,TC(2.23±0.43)mmol/L,LDL-C(1.22±0.31)mmol/L,VLDL(0.39±0.24)mmol/L in group A rats; FBG(13.15±1.18)mmol/L,TG,TC,LDL-C and VLDL-C in group B were all higher than those in group A,HDL-C in group B was lower than that in group A (all P<0.01); TG,TC,LDL-C and VLDL-C in group C were lower than those in group B,HDL-C in group C was higher than that in group B (all P<0.01), FBG(12.70±1.05)mmol/L in group C was unstatistics distinction compared to FBG in group B (P>0.05).3 HWI:The HWI (0.006±0.0003) in group B is higher compared to group A(0.003±0.0002),the HWI (0.004±0.0003) in group C is lower than that of group B(all P<0.01).4 Morphology: HE staining showed that cardiac fiber of group A rats were in order, cross striation was clear, karyon and intercellular space was normal. While in T2DM model rats, cardiac muscle degeneration, focal necrosis and region adipocytes infiltrating could be observed. Foregoing changes in group C rats were more relieved than those in group B rats. PAS staining showed that there was little prunosus masculine matters in the myocardium of group A rats,there were much more prunosus masculine matters in the myocardium of group B rats compared to group A, the prunosus masculine matters in group C rats'myocardium was decreased obviously compared to group B.Masson statining showed that there was little blue masculine matters in the myocardium of group A rats, in the myocardium of group B rats ,there were much more blue masculine matters compared to group A, and accompanied with myofibroblast proliferation,collagen fibers raising,and so on.The blue masculine matters in group C rats'myocardium was decreased obviously compared to group B.The myocardial ultrastructure of group A rats appeared that myofibril was in order, light and dark band was clear and the configuration of mitochondrion was normal. Group B rats had some pathological characteristics of myofibril disorder, mitochondrion edema, endoplasmic reticulum dilatation, CL hyperplasia, hepatin and lipofuscin deposition, capillary basement membrane incrassation, etc. Foregoing changes in group C rats were more relieve than those in group B rats.5 The protein expression of RhoA in myocardium: The IOD (72.01±10.71) of RhoA in group B rats was 1.3 times more than that (31.94±2.72) in group A rats (P<0.01). And the IOD (44.11±6.00) in group C rats was 39.48% less than that in group B rats (P<0.01). Related analysis showed that myocardial RhoA expression had a positive correlation with HWI (r=0.98, P<0.01) in experimental rats.Conclusions1 Without of the coronary artery pathological changes ,the myocardium of T2DM rats showed myocardial hypertrophy,denaturalization,putrescence,mesenchyme fibrosis,muscle degeneration and so on, Which indicated that DCM was a special heart disease.2 The cardiomyopathy of T2DM rats accompanied with the increased of RhoA expression,and it had a positive correlation with the degree of heart hypertrophy,indicates that RhoA was closed to the occurrence and development of DCM.3 Simvastatin based on TC lowering,elicits benefitial effects on cardiovascular diseases by inhibiting RhoA expression.
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