Hsu Jun-Te, Kan Wen-Hong, Hsieh Ya-Ching, Choudhry Mashkoor A, Schwacha Martin G, Bland Kirby I, Chaudry Irshad H
Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35294-0019, USA.
Shock. 2008 Oct;30(4):372-8. doi: 10.1097/SHK.0b013e318164f25c.
Both p38 mitogen-activated protein kinase (p38) activation and protein kinase B (Akt) activation have been reported to regulate glucose transport during myocardial I/R. An increase in cardiac glycogen levels prevents myocardial injury in the ischemic or stressed heart. Although studies have shown that 17"-estradiol (E2)-mediated improvement in cardiac function after trauma-hemorrhage is via p38 activation, it remains unknown whether p38/Akt plays any role in regulation of cardiac glycogen levels under these conditions. To study this, male rats underwent trauma-hemorrhage(mean blood pressure, x40 mmHg for 90 min) followed by fluid resuscitation. At the onset of resuscitation, rats (n=6 per group) were treated with vehicle, E2 (1 mg/kg body weight), the p38 inhibitor SB203580 (2 mg/kg body weight), or E2 and SB203580. Various parameters were measured at 2 h after resuscitation. One-way ANOVA and Tukey test were used for statistical analysis, and differences were considered significant at P<0.05. The depressed cardiac function after trauma-hemorrhage was restored by E2 treatment (P<0.05). Administration of E2 after trauma-hemorrhage also normalized the p38/Akt phosphorylation, which was associated with restoration of cardiac glycogen, glycogen synthase kinase 3"activation, glucose transporter 4 translocation, and increased hexokinase II levels (all parameters, P<0.05). Inhibition of the p38 pathway abolished the E2-induced restoration in above parameters after trauma-hemorrhage. These results suggest that p38-dependent normalization of cardiac Akt phosphorylation and glycogen levels plays an important role in E2-mediated restoration of cardiac function after trauma-hemorrhage.
据报道，p38丝裂原活化蛋白激酶（p38）激活和蛋白激酶B（Akt）激活均参与心肌缺血/再灌注期间的葡萄糖转运调节。心脏糖原水平升高可预防缺血或应激心脏的心肌损伤。尽管研究表明，创伤性出血后17β-雌二醇（E2）介导的心功能改善是通过p38激活实现的，但在这些情况下p38/Akt是否在心脏糖原水平调节中发挥作用仍不清楚。为了研究这一问题，对雄性大鼠进行创伤性出血（平均血压降至40 mmHg，持续90分钟），随后进行液体复苏。在复苏开始时，将大鼠（每组n = 6）分别用溶媒、E2（1 mg/kg体重）、p38抑制剂SB203580（2 mg/kg体重）或E2与SB203580进行处理。在复苏后2小时测量各项参数。采用单因素方差分析和Tukey检验进行统计学分析，P<0.05认为差异具有统计学意义。E2治疗可恢复创伤性出血后降低的心功能（P<0.05）。创伤性出血后给予E2还可使p38/Akt磷酸化正常化，这与心脏糖原恢复、糖原合酶激酶3β激活、葡萄糖转运蛋白4易位以及己糖激酶II水平升高相关（所有参数，P<0.05）。抑制p38通路可消除创伤性出血后E2诱导的上述参数恢复。这些结果表明，p38依赖的心脏Akt磷酸化和糖原水平正常化在E2介导的创伤性出血后心功能恢复中起重要作用。
