The Protective Effects Of Probucol On Experimental Diabetic Rat Hearts

ObjectiveIn this study,we observe the expression of GLUT4 and PKB,GLUT4mRNA,the changes of the activity of Na⁺-K⁺-ATPase,Ca⁺⁺-Mg⁺⁺- ATPase in the experimental rat hearts and the prevention effects of probucol,the possible mechanism was explored also.Methods36 Healthy SD male rats,divided into two groups randomly:Group E(normal control group,10 rats),Group A+C(the diets enriched with fat and sugar 8 weeks,26 rats). At the eighth weekend,using the STZ to establish the T2DM rat model,then the rats were redivided into Group E(normal control group,10 rats),group A(the diets enriched with fat and sugar 8 weeks plus low dose STZ induced T2DM rat model successfully and then probucol 500mg/kg/d intervence for 8 weeks,11 rats),Group C(the diets enriched with fat and sugar 8 weeks plus low dose STZ induced T2DM rat model 8 weeks,12 rats).The rats were given the high-glucose-fat diets for 8 weeks, all the rats were killed.The day before killing,OGTT was tested.The serum lipid,MDA,SOD,GSH-Px were tested.The activity of Na⁺-K⁺-ATPase,Ca⁺⁺-Mg⁺⁺-ATPase were tested.The expression of GLUT4,PKB in the rat hearts were tested by immunohistochemistry.The expression of GLUT4 was tested by RT-PCR also.All data were analyzed using SPSS 13.0 PC program for windows.ResultsOGTT:Insulin:there were no significant difference(all the P values＞0.05)at 0min,30min,60min,120min between group A,C and E respectively;blood glucose: at 0 min there was no significant difference(all the P values＞0.05)between group A,C and E respectively;At 30min,60min and 120min,the blood glucose of group A and C were significant higher than group E,the blood glucose of group A were significant lower than group C(all the P values＜0.05).The serum TG,TC,LDL -C of group A,C were significant higher than group E(P＜0.05,P＜0.05,P＜0.05,respectively),the serum TC and LDL-C of group A were significant lower than group C(P＜0.05, P＜0.05,respectively).The serum MDA of group C was significant higher than group E(P＜0.05),the serum MDA of group A was significant lower than group C(P＜0.05), the activity of SOD and GSH-Px of group C were significant lower than group E(P＜0.05,P＜0.05,respectively),the activity of SOD and GSH-Px of group A were significant higher than group C(P＜0.05,P＜0.05,respectively).The activity of Na⁺ -K⁺-ATPase,Ca⁺⁺-Mg⁺⁺- ATPase of cardiac muscle in group C were significant lower than group E(P＜0.05,P＜0.05,respectively),the activity of Na⁺-K⁺-ATPase and Ca⁺⁺-Mg⁺⁺- ATPase in group A were significant higher than group C(P＜0.05, P＜0.05,respectively).The expression of protein level of GLUT4 in group C was significant lower than group E(P＜0.05),the expression of protein level of GLUT4 in group A was significant higher than group C(P＜0.05),the expression of protein level of PKB has no significant difference between group A and group C(P＞0.05),but group C was significant lower than group E(P＜0.05).The expression of mRNA level of GLUT4 in group C was significant lower than group E(P＜0.05),the expression of mRNA level of GLUT4 in group A was significant higher than group C(P＜0.05).Conclusion1.The protein level and mRNA level of GLUT4,the protein level of PKB express lower in T2DM model rats cardiac muscle,and the activity of Na⁺-K⁺-ATP and Ca⁺⁺-Mg⁺⁺- ATP were lower in T2DM rats cardiac muscle.2.Probucol can increase the protein and mRNA level of GLUT4,the activity of Na⁺-K⁺-ATPase and Ca⁺⁺-Mg⁺⁺- ATPase in T2DM rats cardiac muscle.The mechanism could refer to the decreased TC,LDL and oxidative stress.3.Probucol can influence the diabetes cardiomyopathy by increasing the protein level and mRNA level of GLUT4,the activity of Na⁺ -K⁺-ATPase and Ca⁺⁺-Mg⁺⁺- ATPase in T2DM rats cardiac muscle.