Effect Of Simvastatin On The Calcium-regulatory Proteins And Cardiac Dysfunction In Rats With Diabetes

OBJECTIVETo investigate the effect of simvastatin on myocardial calcium homeostasis, cardiac function,serum cholesterol level.METHODSMale 8-week-old Sprague-Dawley(SD) rats were divides into two groups.A group of rats was rendered diabetic with a single intraperitoneal injection streptozotocin in citrate buffer(Random blood glucose＞16.7mmol/L).Half of the rats with diabetes were kept with simvastatin,and the others were kept with 0.9%NS for up to 3 months.SD rats were used as normotensive controls.After 3 months,rats were anaesthetized and the arterial hemodynamic parameters were measured via a polyethylene tube filled with heparine/saline solution inserted into the right carotid artery.Left ventricular peak pressure(LVSP),left ventricular end-diastolic pressure(LVEDP),the maximal rate of rise and fall of pressure(+dp/dtmax and -dp/dtmax),as well as the concentrations of serum total cholesterol(TC),triglyceride(TG),HDL and LDL level were determined after the treatment.The protein expression of sarcoplasmic reticulum Ca^2+- ATPase (SERCA2a) and(phospholamban) PLB was also evaluated. ResultsFirstly,after simvastatin treatment,LVSP,+dp/dtmax,-dp/dtmax were significantly decreased,whereas LVEDP were remarkably increased in the DM group compared with SIM group(P＜0.05).However,no differences were found between SIM group and SD group.(DM SIM SD groups LVSP 83.3±10.0mmhg,104.3±14.9mmhg, 114.2±14.9mmhg,LVEDP 14.5±3.7mmhg,6.7±4.6mmhg,4.4±4.0mmhg, +dp/dtmax 2151±454,4856±1281,5361±783,-dp/dtmax 2229±450,3465±1043, 4263±801).Secondly,serum concentrations of TC,TG,HDL,and LDL were no significant difference between DM and SIM groups.However,the level of TG and LDL in SD group is much lower and HDL is remarkably higher than in SIM and DM groups(P＜0.05),but the level of TC were no difference among three groups.(DM SIM SD groups TG 116±49mg/dl,131±34 mg/dl,66±27 mg/dl,TC 62±8 mg/dl, 67±4.6 mg/dl,73±17 mg/dl,LDL 25±19 mg/dl,28±15.1 mg/dl,8±5 mg/dl, HDL 41±13 mg/dl,36±15mg/dl,61±11mg/dl).Furthermore,simvastatin prevented the decrease of SERCA2a,but showed no effect on PLB expression.These effects might be independent of its lipid-lowering effect.