·糖尿病基础研究·

　　　　【摘要】 目的 探讨PTEN在糖尿病心肌缺血再灌注及后处理中的作用。 方法 SD大鼠117只随机分为非糖尿病(NDM)组39只和糖尿病(DM)组78只，其中NDM组分为假手术(NDM+S)亚组、缺血再灌注(NDM+IR)亚组和缺血后处理(NDM+IPo)亚组;DM组分为假手术(DM+S)亚组、缺血再灌注(DM+IR)亚组、缺血后处理(DM+IPo)亚组、PTEN抑制剂BPV+假手术(B+DM+S)亚组、BPV+缺血再灌注(B+DM+IR)亚组和BPV+缺血后处理(B+DM+IPo)组。建立心肌缺血再灌注模型，BPV缺血前1 h静脉注射。免疫组织化学染色法分析心肌PTEN、PI-3K、p-Akt的表达;TTC法检测心肌梗死面积;TUNEL法检测心肌细胞凋亡;光镜下观察心脏组织病理结果。 结果 与NDM+IR亚组比较，NDM+IPo亚组心肌PTEN表达减少[(0.130±0.024) vs (0.148±0.023)，P<0.05]，PI-3K和p-Akt表达增高[(0.142±0.027) vs (0.112±0.020);(0.137±0.020) vs (0.115±0.021)，P<0.05]，心肌细胞凋亡指数及心梗面积减少[(16.69±1.90) vs (20.77±0.10);(35.02±3.11) vs (41.10±2.07)，P<0.05]。与DM+IR亚组比较，DM+IPo亚组心肌PTEN、PI-3K、p-Akt表达，心肌细胞凋亡指数及心梗面积均无明显改变，差异无统计学意义(P>0.05);与DM+S、DM+IR、DM+IPO亚组比较，BPV干预各亚组心肌PI-3K和p-Akt表达均升高，心肌细胞凋亡指数及心梗面积均减少(P<0.05)。 结论 糖尿病心肌缺血再灌注期间心肌PTEN高表达是造成PI-3K/Akt信号通路失活重要因素，可能导致IPo对心肌IRI的保护作用丧失。

　　【关键词】 糖尿病;缺血再灌注损伤;缺血后处理;PTEN;PTEN抑制剂

　　【Abstract】 Objective To explore the effect of PTEN in ischemia-reperfusion injury and postconditioning of diabetes myocardial. Methods 117 healthy sprague dawley rats were randomly divided into NDM group(n=39) and DM group(n=78). The rats were randomly divided into 6 subgroups: NDM+S, NDM+IR, NDM+IPo, DM+S, DM+IR and DM+IPo subgroups. Ischemia-reperfusion model was builded and PTEN inhibitors was intravenous injection before ischemia 1 hours. The expression of PTEN, PI-3K, p-Akt was analyzed by immunohistochemical. Infarct size was assessed by TTC staining. Cardiomyocyte apoptosis was detected by TUNEL method. Results The expression of PTEN was lower[(0.130±0.024) vs (0.148±0.023)，P<0.05], PI-3K, p-Akt was higher[(0.142±0.027) vs (0.112±0.020);(0.137±0.020) vs (0.115±0.021)，P<0.05] and the apoptotic index and the myocardial infract size was lower in NDM+IPo subgroups than in NDM+IR subgroup. There were no significant differences in the expression of PTEN、PI-3K、p-Akt, and apoptotic index and the myocardial infract size between DM+IR and DM+IPo groups(P>0.05). Compared to the BPV non-intervention groups, BPV intervention groups showed that the expression of the PI-3Kand p-Akt was increased and the apoptotic index and the myocardial infract size was decreased(P<0.05). Conclusion The high expression of myocardial PTEN is an important factor of causing the inactivate PI-3K/Akt signaling pathway and may be lead to the declined protection of IPo on myocardial IRI.

　　【Key words】 Diabetes mellitus; Ischemia-reperfusion injury; Ischemic postconditioning; PTEN; BPV