| Objective :Type 2 diabetic cardiomyopathy rat model was builded by the method of high fat and high sugar diet loading with intra-peritoneal injection of STZ,in order to study the protective effect of taurine on the myocardium of diabetic cardiomyopathy rats and discuss the protective effect of tauine on diabetic myocardium in terms of molecular mechanism.Methods : Eighty male SD rats were randomly divided into two groups: Control group(17 rats)and High fat and high glucose group(63 rats) after one week of adaptive feeding. Rats in high fat and high glucose group were fed with high fat and high glucose diet, meanwhile rats in normal group were fed with normal diet for 8 weeks. Then rats in high fat and high glucose group were inject 1% STZ intraperitioneally with a dose of 30mg/kg, meanwhile rats in normal group were injected with the same volume of citric acid sodium citrate buffer solution. Fasting blood glucose was measured at 3days and 7days after intraperitoneal injection of STZ. The diagnostic criteria for success in the diabetes model: Two consecutive fasting biood glucose?11.6 mmol/L. Unsuccessful rats were injected intraperitoneal STZ once again. A low dose of STZ was used to establish the rat model of diabetic cardiomyopathy. In 12 weeks, a total of 45 rats were successfully established. The diabetic rats were divided into three groups: diabetic cardiomyopathy group(DCM),low dosage taurine intervention group(DCM+ taurine 200mg/kg), and high dosage taurine intervention group(DCM+ taurine 400mg/kg).After 8 weeks of drug treatment, weighing the rats, then anesthetized rats with 10% Hydrate hydrate.Blood was taken from abdominal anorta, then open the chest with scissors. The heart was removed immediately, then to weight the heart. To observe the effect of taurine on body weight, Heart weight/Body weight,blood glucose,blood lipids(Triglyceride,Total Cholestorol, High density lipoprotein cholesterol,Low density lipoprotein cholesterol)and myocardial enzymes(Aspartate transaminase,Creatine kinase, Creatine kinase isoenzyme, Lactate dehydrogenase,?-hydroxybutyrate dehydrogenase) in DCM rats. To observe the changes of myocardial microstructure were observed in each group with the method of HE dyeing. To observe the changes of myocardial microvascular density with the method of CD31 immuno histochemisty dyeing. To detect the changes of the expression levels of 3 cardiac muscle specific mi RNA with RT-PCR.Results:(1) Compared with the normal group, the DCM rats showed no shiny hair, multi drink, eat more, and more urine and other symptoms.(2)At the end of the experiment, the weight of model group rats decreased obviously; Compared with the normal group, model group rats' HW/BW, blood glucose, blood lipid(TG?TC?HDL-C)? myocardial enzyme(CK?CK-MB?LDH-L??-HBD) were increased significantly(P<0.05), LDL- C was significantly lower than normal group(P<0.05); Compared with the model group, taurine intervention group rat HW/BW, blood glucose, blood lipid(TG, TC, HDL- C), myocardial enzymes(CK, CK- MB, LDH-l, alpha HBD) were significantly reduced(P<0.05), LDL-C is significantly higher than the normal group(P<0.05).(3) The myocardial structural are shown : Well organized, typical symmetric myofibrils were seen in control rats; Myocardial cell was arranged disorderly in model group rats; cell vacuoles degeneration was visible, microvascular basement membrane was thicken; High dose group rats myocardial fibers were complete, myocardial cells were arranged neatly in the model group, almost no cell vacuoles degeneration was visible.(4) CD31 immuno histochemical staining showed that the normal rats appears more blood vessels; In model group rats myocardial microvascular significantly was reduced, MVD was 60% lower than the normal group(P < 0.01); myocardial MVD in high dose group rat was increased by 56%(P < 0.01) than the model group.(5) The changement of micro RNA expressional level: compared with normal group, in model group rats the expression level of mi RNA-208 a,mi RNA-499,micro RNA-214 were significantly increased(P< 0.05); Compared with model group, the expression level of mi RNA-208 a, mi RNA-499, micro RNA-214 were significantly reduced in taurine intervention group(P< 0.05).Conclusion : The type 2 diabetic cardiomyopathy in rats mode was prepared successfully with the measure of high sugar, high fat diet feeding in combination with small dose of STZ intraperitoneal injection. These results suggest that taurine may have great therapeutic potential in the treatment of DCM, the mechanism may be related to improve myocardial energy metabolic abnormalities, the inhibition of myocardial microvascular lesion, change of mi RNAs in myocardial expression. |
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