The Effects Of Peroxisome Priliferator Activated Receptorα On Diabetic Rat's Cardiomyocyte Apoptosis And Its Mechanism

PART ONE Effect of PPARα's nuclear activation on the rat cardiomyocytes'apoptosis which cultured in glucose and fatty acidObjective: To investigate the effects of PPARαagonist in the apoptosis of cultured rat cardiomyocyte with glucose and fatty acid injury.Methods: In the cultured cardiomyocytes were maintained in medium and were divided into 3 groups: Group N (The cardiomyocytes were exposed to hypoglycemia type DMEM alone); Group H (The cardiomyocytes were exposed to hyperglycemia type DMEM and treated with palmitic acid and oleic acid); Group I (The cardiomyocytes were exposed to hyperglycemia type DMEM and treated with palmitic acid and oleic acid, also Wy14643). Apoptosis was detected by TUNEL, immunocytochemistry staining was used to detect each groups of cardiomyocytes in PPARα's expressing site, and western blotting was used to detect each groups of cardiomyocytes in PPARαand NF-κB's expression of its protein level.Result:The number of apoptosis cardiomyocytes is increased in group H, the expression of nucleus NF-κB in protein level is increased(all these are compared with N group, P<0.01), but the PPARα's expression is not different, even the immunocytochemistry show that the nuclear expression of PPARαis staining more in H group compared to the N group;And after activated PPARαin I group, the number of apoptosis cardiomyocytes is reduced distinctly(compared to H group, P<0.01). Immunocytochemistry show that the nuclear expression of PPARαis staining more in I group compared to the H group, and western blotting are declared that the nuclear PPARαof I group is more than H group(P<0.05), the NF-κB is decreased(P<0.01), and the number of apoptosis cardiomyocytes of H group are more than I group(P<0.01).Conclusion: The augmentation of nuclear PPARαmight be involved in the inhabitation of the apoptosis in cardiomyocytes which incubated with glucose and fatty acid,suggesting it may participate in the hyperglycemia and hyperlipoproteinemia's self-protection.PART TWO Effect of the Nuclear overexpression of PPARαon the Apoptosis of type 2 diabetic Rat cardiomyocytesObjective: To investigate the overexpression of PPARαin the Apoptosis of rat Cardiomyocyte with type 2 diabetes.Methods: All the rats were divided into 2 groups: Group N (control group); Group D (type 2 diabeies group). After 16 weeks breeding, apoptosis was detected by TUNEL, immunohistochemistry staining and western blotting were used to detected each group's Cardiomyocyte about PPARαand NF-κB in the expression of protein level.Result: The number of apoptosis were increased in group D, the expression of PPARαand NF-κB in protein level were increased, also the nucleus were staining more(p<0.01).Conclusion: In the type 2 diabetes rat's heart, the increased overexpression of nuclear PPARαmight be involved in the regulation of the apoptosis in cardiomyocyte,suggesting it may participate in the development of diabetic cadiomyopathy.