| Objective: Researchers found that the patients of diabetes mellitus (DM)have more chances to become heart failure in records. Diabetic cardiomyopathy(DCM) is one of the reason. Apoptosis plays an important role in the happenning and development of cardiomypathy . In this study we treated type-2 diabetic rats with simvastatin to find whether Bcl-2 and P53 would changed again and how .This study aims to observe the changes of the genes and corresponding proteins in order to find out whether simvastatin can protect the heart .Simvastatin belongs to the inhibitor of 3-hydroxy- 3-methylglutary CoA(HMG-CoA)reductase . It can lower blood fat, improve the fuction of blood vessel endothelium, inhibit the inflammation of atheromatous plaque, increase the stability of atheromatous plaque, suppress the thrombosis. Besides it can also influece the growth and proliferation of cells according to papers. Moreover it also protect cerebral vessels.Then does it protect the heart? This is not very clear. Metformin is the classic in clinic. But whether it protect the heart is not known.In this experiment, we set up the model of type 2 diabetic rats. Then we treated them with Simvastatin and Metformin to observe the relative expression of Bcl-2, P53,and correponding proteins. The significance of this study is very important in the prevention and cure of heart failure which happens in the patients of diabetic 2.Methods:1 AnimalMale SD rats (body weight 200-220g) were randomly divided into control group (Con) Insulin resistance group (IR) diabetic group (DM). Besides the rats in control group, all the other rats were feed on high fat food. Until they emerged insulin resistance, the rats were injected intraperitoneally with streptozotocin (STZ, 27mg/kg), dissolved in 0.1M citrate buffer (pH4.2). At the 72th hour after the injection of STZ, the rats whose fasting blood glucose concentration exceeded 7.8 mmol/L were considered diabetic. The rats in Con and IR received the corresponding volume of citrate buffer. Then the rats in DM group were divied randomly into DM group Metformin group(MT) and Simvastatin group(S). All the rats were sacrificed 6 weeks after diabetes induction. At the same time the rats in MT and S group were treated with Metformin and Simvastatin differently while those in DM group were treated with normal sodium.After fasting overnight, the rats were under 25% urethane anesthesia (6ml/kg). Open the thoracic cavity quickly. Heart tissues were removed and rinsed with normal saline. And then it was immediately submerged in liquid Nitrogen, then stored at -80℃for the extraction of total RNA..2 Assay of blood glucose Blood glucose concentration were measured by kit using oxidase method.3 Assay of mRNA expression Heart total RNA was extracted by Trigol regent. The relative mRNA content was measured by RT-PCR using GAPDH as inner standard.4 Assay of proteins expressionHeart total proteins was extracted. The relative protein content was measured by Western blot usingβ-actin as inner standard.5 Statistical analysisData were expressed as mean±SEM. SPSS13.0 soft ware was used. Statistical comparisons were made by one-way ANOVA. A value of P<0.05 was considered significant.Results:1 OGTT experiment show that insulin resistance occur in IR and D group.2 Changes of fasting blood glucose (FBG) at the 72th hour after the STZ injection.At the 72th hour after the STZ injection, FBG in DM group (14.49±3.67mmol/L) was significantly higher than that in Con group (5.25±0.43 mmol/L,P<0.05). It indicated that type 2 diabetic rats were successfully established.3 Changes of mRNA expression of Bcl-2,P53 of four group rats3.1 The relative expression of Bcl-2 mRNA in heartThe relative expression of Bcl-2 mRNA in C, IR and D were respectively 0.5882±0.1287, 0.6345±0.0894, 1.0107±0.1190,0.4148±0.1170. The relative expression of Bcl-2 mRNA in Con and DM was higher than that in S (P<0.05).3.2 The relative expression of P53 mRNA in heartThe relative expression of P53 mRNA in Con, DM, MT and S were respectively 0.6729±0.0933, 0.6255±0.0365, 0.6992±0.0606, 0.5147±0.0599. The relative expression of P53 mRNA in Con and DM was higher than that in S (P<0.05).4 Changes of protein expression of Bcl-2,P53 of four group rats4.1 The relative expression of Bcl-2 protein in heart The relative expression of Bcl-2 protein in Con, DM, MT and S were respectively 0.6082±0.3827, 0.6253±0.0735, 0.9872±0.1359, 0.5023±0.0926. The relative expression of Bcl-2 protein in S was lower than that in Con and DM (P<0.05 ).4.2 The relative expression of P53 mRNA in heart The relative expression of P27 mRNA in Con, DM, MT and S were respectively 0.7352±0.0874, 0.7885±0.0923, 0.8002±0.0688, 0.6354±0.0675. The relative expression of P53 protein in S was lower than that in Con and DM (P<0.05 and P<0.01).Conclusion:1 The occuring of diabetic cardiomyopathy is related to the genes about proliferation and apoptosis.2 The role of Simvastatin in protecting heart is inferior to Metformin. It can only lower Triglyceride and cholesterol . Metformin can lower blood gulucose and maybe change genes. But the mechanism of Metformin is not clear.
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