Protective Action Of Taurine On The Myocardial Damage Of Diabete Rats

Objective :To observe the characters of the myocardial damage of diabete rats and the changes of expression of endoplasmic reticulum stress signal protein (glucose-regulated protein 78kD,Grp78 and glucose-regulated protein 94kD,Grp94) through building the animal model of type 2 diabetes mellitus rats.Thus we can study the relations of endoplasmic reticulum stress and the myocardial damage of diabete rats,and protective action of taurine on the myocardial damage of diabete rats.It will base for studying the pathogenesy and prevention of the diabetes.Methods:A total of 40 healthy male Wistar rats weighting 140-160g were used,which were randomly chosen to be normal control group(C),high glucose and fat group(H),diabetic model group(M),and taurine treat group (T).C are fed on common forage ,while M and T are feed on high glucose and fat forage for 5 weeks were induced to be diabetes mellitus by STZ accoding to 40mg/kg dose which was injected into abdomens .After 4 weeks, athe diabetic model was successfully established , from which 10 rats were randomly chosen to be taurine treat group , which accept the taurine treat by intragasitric adminstation accoding to 200mg/kg.day for 5 weeks. The rest 10 rats regard as diabetes model group. Eventualy, all rats were killed and obtain from the hearts to inspect all kinds of blood index including the blood glucose, the serum insulin,CK and LDH,and then their myocardium were dissected.The immunhistochemistry method was used to measure the expression Grp78 and Grp94 and reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the content of Grp78mRNA, Grp94 mRNA, Caspase12mRNA, and Caspase3mRNA and observe the pathologic changes. Results:1 The mental state of the taurine treat group is better than the diabetes model group . The diabetes model group and the high glucose and fat diet group increase weight significantly compare to C group(P<0.01). after 3 weeks, the diabetes model group and he high glucose and fat diet group's body weight gain is more than C group rats.2 The fast blood glucose (FBG, mmol/l) of the high glucose and fat diet group increase slightly higher than the normal control group, but it have no statistically significant. FBG increased slightly in the diabetes (P>0.05). The fast blood insulin and insulin resistance index of the high glucose and fat diet group and the diabetes model group exceed significantly to the normal control group (P<0.01).3 The result of the serum biochemistry detection indicate that CK and LDH activity step up obviously compare to the normal control group (P<0.01), to which the taurine treat group appear to decrease slightly contrasting (P<0.05)4 The staining of HE showed the model group rat's myocardial fiber soluted, degenerated and necrosed partly, while the taurine treat group decrease obveriously the above-mention pathological changes.5 Comparing to the normal control group,the number of the post stained Grp78 and Grp94 protein in the diabetes model group increase significantly,and the post index of immunohistochemistry of Grp78 and Grp94 protein step up obviously(P<0.01).Contrasting with the diabetes model group,the number of the post stained particles and the post index of immunohistochemistry of Grp78 and Grp94 protein cut down significantly(P<0.01).6 The demi-quantitate RT-PCR showed that Grp78mRNA, Grp94mRNA, Caspase-12mRNA and Caspase-3 mRNA was up-regulated in the diabetes model group and the taurine treat group. the ratio of RT-PCR products of the diabetes model group to GAPDH was 0.891±0.049,0.823±0.035 and0.602±0.020,0.795±0.015, respectively, which was significant difference compared with control group(P<0.01). The ratio of RT-PCR products of the taurine treat group to GAPDH was0.414±0.065, 0.257±0.028, 0.258±0.029 and 0.262±0.015 respectively, which was significant difference compared with control group( P<0.01)and lower expression than the ratio of RT-PCR products of the diabetes model group.Conclusion:The Wistar model of T2DM accompanied by myocardial damage are built successfully by feeding on high glucose and fat diet and low dose of STZ(35mg/kg).Under the continual state of stress such as high blood glucose, endoplasmic reticulum stress (ERS) participate in the course of myocardial damage, as well as promote to diabetic myocardial cells apoptosis. Taurine could improve diabetic myocardial damage.The possible mechanism is that it could decrease diabetic myocardial cells apoptosis through furthermore decrease the expression of ERS through cuting down the reaction of ERS and down regulating the expression of Caspase-12 and Caspase-3.