糖尿病患者缺血性心脏病的发病率及病死率均显著增高，表现为心肌缺血易损；而保护性蛋白激酶活性降低是导致糖尿病心肌缺血损伤加重的重要原因。蛋白磷酸酶PHLPP1可使保护性蛋白激酶Akt去磷酸化失活，导致心肌细胞凋亡。研究报道，糖尿病患者胰岛素抵抗程度与PHLPP1表达正相关。我们目前的研究发现，ob/ob小鼠心肌PHLPP1本底水平较野生型小鼠上调，缺血/再灌注后PHLPP1表达下调，但PHLPP1向线粒体转位增强；提示：糖尿病心肌中PHLPP1的表达及线粒体转位可能是糖尿病心肌缺血易损的原因。本课题拟在前期研究基础上: ①明确糖尿病心肌PHLPP1的表达变化及细胞内转位；②阐明PHLPP1在心肌胰岛素抵抗以及糖尿病心肌缺血损伤中的功能和调控机制；以期为防治糖尿病缺血性心脏病提供新的理论依据。

Diabetes has been strongly associated with increased morbidity and mortality of ischemic cardiovascular disease, eliciting myocardial ischemic vulnerability. The suppressed activity of protective protein kinase plays a critical role in aggravated ischemic injury of diabetic heart. PHLPP1 dephosphorylates protective protein kinase Akt, resulting in cardiomyocytes apoptosis. Meanwhile, some research demonstrated that PHLPP1 abundance is significantly related to insulin resistance. Our recent study found that basal PHLPP1 protein level in ob/ob mice heart upregulated and decreased following ischemia/reperfusion(I/R)，and myocardial I/R enhanced translocation of PHLPP1 to mitochondrion in diabetic heart, suggesting that the expression and translocation of PHLPP1 might be the potential mechanism of myocardial ischemic vulnerability in diabetes. Therefore, the aims of our study were: ①to explicit the expression state and cellular translocation of PHLPP1 in diabetic heart; ②to clarify the role and regulatory mechanism of PHLPP1 in cardiac insulin resistance and diabetic-related ischemic intolerance. In order to provide theoretical basis for prevention and treatment of diabetic ischemic cardiovascular disease.