【摘要】 目的探讨高表达热休克蛋白A12B(HspA12B)对内毒素血症所致心功能不全的保护作用及其可能机制。方法 HspA12B转基因小鼠和野生型小鼠均分别注射脂多糖(LPS)10mg/kg(A1组,15只;A2组,14只)、渥曼青霉素(WM)1mg/kg+LPS 10mg/kg(B1组,10只;B2组,10只)、生理盐水(C1组,8只;C2组,9只)。用超声心动图测定左心室射血分数(LVEF)和短轴缩短率(FS),Western blot法检测Akt、磷酸化Akt(p-Akt)、糖原合成酶激酶3β(GSK-3β)、磷酸化GSK-3β(p-GSK-3β)蛋白表达。结果 A1、A2组p-Akt、p-GSK-3β表达分别低于C1、C2组(P<0.01或P<0.05);与A2组相比,A1组p-Akt、p-GSK-3β的下降程度分别减轻了54.3%、27.4%(P<0.05)。各组LVEF、FS水平由多到少为C1组>A1组>B1组、C2组>A2组>B2组(P<0.01);A1组LVEF、FS较A2组分别提高了56.0%、72.5%(P<0.01)。结论高表达HspA12B改善内毒素血症心功能不全可能是通过激活PI3K/Akt信号通路介导的。更多还原

【Abstract】 Objective To investigate the protective effect and underlying mechanism of heat shock protein A12B(HspA12B) overexpression on cardiac dysfunction induced by endotoxemia in mice.Methods Thirty-three HspA12B transgene(Tg) mice were divided into groups of A1(15 mice,injected with LPS 10 mg/kg),B1(10 mice,injected with wortmannin 1 mg/kg for 1 h before LPS 10 mg/kg) and C1(8 mice,injected with normal saline).So did wild type(WT) mice,named as groups of A2(14 mice),B2(10 mice) and C2(9 mice),respectively.The left ventricular ejection fraction(LVEF) and fractional shortening(FS) were measured by echocardiography.The protein expressions of Akt,p-Akt,GSK-3β and p-GSK-3β were detected by Western blot.Results The protein expressions of p-Akt and p-GSK-3β in groups of A1 and A2 were lower than those in groups of C1 and C2,respectively(P<0.01 or P<0.05).Compared with group A2,the decrease in protein expressions of p-Akt and p-GSK-3β was decreased by 54.3% and 27.4% in group A1(P<0.05).The increases in LVEF and FS were in an order of group C1>group A1>group B1,and group C2>group A2>group B2(P<0.01).Compared with group A2,LVEF and FS were increased by 56.0% and 72.5% in group A1(P<0.01).Conclusion HspA12B overexpression can improve cardiac dysfunction induced by endotoxemia,probably via activation of PI3K/Akt signaling pathway.更多还原