甲状腺素预处理对大鼠肝脏缺血／再灌注后热休克蛋白70表达的信号研究

Signaling pathway regulating HSP70 in thyroxine pretreated liver ischemia/reperfusion rats

目的探讨甲状腺素能否通过对PI3 K-Akt信号通路的活化，上调热休克蛋白70（HSP70），对缺血/再灌注（ischemia/reperfusion， I/R）损伤的大鼠肝脏发挥保护作用。方法建立大鼠肝脏I/R模型（缺血30min，再灌注48h），将雌性Wistar大鼠随机分为假手术组、I/R组和处理组。处理方法为缺血前48h于腹腔注射0．1mg/kg甲状腺素。再灌注后检测肝组织丙二醛（ MDA）含量，血清肿瘤坏死因子-α（ TNF-α）、丙氨酸转氨酶（ ALT）和天冬氨酸转氨酶（ AST）浓度，用蛋白质免疫印迹法检测肝组织HSP70含量表达、总Akt、磷酸化Akt（ P-Akt）水平。结果与假手术组比较，I/R组血中ALT、AST、TNF-α和MDA含量均显著升高（ P＜0．05）。与I/R组比较，处理组各指标水平均显著降低，但较假手术组高（P＜0．05）。假手术组有少量HSP70和磷酸化Akt表达，处理组HSP70表达及Akt磷酸化水平均高于I/R组（P＜0．05）。结论甲状腺素可能通过PI3K-Akt信号通路诱导多量HSP70表达，在大鼠肝脏I/R损伤中发挥细胞保护的作用。

Objective To explore the effect of thyroid hormone via PI3K-Akt pathway on heat shock protein 70 （HSP70） after liver ischemia reperfusion （I/R） injury in rats.Methods An I/R process of 30 minutes ischemia and then 48 hours reperfusion was established in female Wistar rats.The 30 rats were randomly divided into three groups：sham-operated, I/R and treatment group.Treatment of 0.1 mg/kg intraperitoneal injection of T3 at 48 hours before ischemia.The levels of MDA in liver tissue and ALT, AST and TNF-αin serum were detected at reperfusion for 48 hours.The expression of HSP70, total Akt protein and P-Akt protein were examined by Western blot.Results Compared to the I/R group, the level of ALT, AST, TNF-αin serum samples and MDA in liver tissue were lower in the other two groups （ P〈0.05 ） , but they were higher in the treatment group than sham -operated group （P〈0.05）.The expression of HSP70 and the phosphorylation level of Akt were highest in the treatment group （ P〈0.05 ） .Conclusion These results indicate that thyroid hormone up-regulates the expression of HSP70 through activation of PI3K-Akt pathway and subsequently decreases the liver ischemia reperfusion injury in rats.