PTEN在缺血后处理对糖尿病缺血再灌注心肌失敏感性中的作用及机制  

Effect and mechanism of PTEN in declined protection of ischemic postconditioning on myocardium of ischemic reperfusion in diabetic rat

作　　者：刘珍珍[1] 夏中元[1] 赵博[1] 薛锐[1] 吴洋[1] 刘慧敏[1] 刘敏[1] 

机构地区：[1]武汉大学人民医院麻醉科,430060

出　　处：《中国糖尿病杂志》2015年第3期263-266,共4页Chinese Journal of Diabetes

基　　金：国家自然科学基金(81170768)

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抑制剂双过氧钒(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1h静脉注射。免疫组织化学染色法分析心肌PTEN、磷脂酰肌醇3激酶(PI-3K)、蛋白激酶B(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肌梗死面积减少[(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肌梗死面积均无明显改变(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信号通路失活的重要因素,可能导致IPo对心肌IRI的保护作用丧失。Objective To explore the effect of PTEN in ischemia-reperfusion injury and postconditioning of diabetes myocardial. Methods 117 healthy spraguedawley 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- reper[usion model was huilded and PTEN inhibitors was in chemia for 1 hours. The expression of PTEN, PI-3K,p-Akt was analyzed by immunohistochemical staining. Infarct size was assessed by TTC staining. Cardiomyocyte apoptosis was detected by TUNEL method. Results In NDM＋IPo versus NDM＋IR subgroup, 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 apoptotie index and the myocardial infract size was lower. 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 subgroups（P〉0. 05）. Compared to the BPV non-intervention groups, BPV intervention groupsshowed that the expression of the PI-3Kand p-Akt was increased and the apoptotie index and the myocardial infract size was decreased（P〈0.05）. Conclusion The high expression of myocardial PTEN is an important factor for causing the inactivate PI-3K/Akt signaling pathway and may lead to the deelined protection of IPo on myocardial IRI.

关 键 词：糖尿病 缺血再灌注损伤 缺血后处理 PTEN 双过氧钒 

分 类 号：R587.2[医药卫生—内分泌]