β-arrestin-2通过上调PI3K/Akt信号抑制自噬以减轻小鼠肝脏缺血-再灌注损伤

β-arrestin-2 inhibits autophagy by up-regulating PI3K/Akt signal to alleviate liver ischemia-reperfusion injury in mice

    摘要
  • 摘要:
      目的  验证β-arrestin-2是否通过上调PI3K/Akt信号抑制自噬对小鼠肝脏缺血-再灌注损伤（IRI）发挥保护作用。
      方法  将C57BL/6背景的β-arrestin-2基因敲除（KO）及野生型（WT）小鼠各12只，随机分为KO小鼠假手术组（KO+sham组），KO小鼠IRI组（KO+IRI组），WT小鼠假手术组（WT+sham组）和WT小鼠IRI组（WT+IRI组），每组各6只。分别建立70%肝脏IRI模型或进行假手术处理，于肝脏再灌注或手术后6 h进行相关研究。采用免疫组织化学（免疫组化）染色检测凋亡信号蛋白裂解半胱氨酸天冬氨酸蛋白酶3（cleaved Caspase-3）、增殖信号蛋白Ki-67及PI3K/Akt通路信号蛋白p-Akt的表达。
      结果  免疫组化染色结果显示，与相应的sham组比较，KO+IRI组和WT+IRI组小鼠肝组织中的cleaved Caspase-3、Ki-67和p-Akt阳性细胞计数均增加（均为P < 0.01）；与WT+IRI组比较，KO+IRI组小鼠肝组织中cleaved Caspase-3阳性细胞计数增加，Ki-67和p-Akt阳性细胞计数均减少（均为P < 0.05）。
      结论  β-arrestin-2可减轻小鼠IRI后肝细胞凋亡、促进其损伤修复，其通过上调PI3K/Akt信号抑制自噬来减轻小鼠肝脏IRI。

     

    Abstract:
      Objective  To verify whether β-arrestin-2 inhibits autophagy by up-regulating PI3K/Akt signal to protect the liver from ischemia-reperfusion injury (IRI) in mice.
      Methods  Twelve β-arrestin-2 knockout (KO) and twelve wild-type (WT) C57BL/6 mice were randomly divided into the KO+sham group, KO+IRI group, WT+sham group and WT+IRI group, six mice in each group. The mouse models with 70% liver IRI were established or sham operation was performed. Relevant experiments were carried out at 6 h after liver reperfusion or operation. The expression levels of apoptosis signal protein cleaved Caspase-3, proliferation signal protein Ki-67 and the PI3K/Akt signal protein p-Akt were detected by immunohistochemical staining.
      Results  Immunohistochemical staining demonstrated that compared with the corresponding sham group, the positive cell count for cleaved Caspase-3, Ki-67 and p-Akt in liver tissues of mice was significantly increased in the KO+IRI and WT+IRI groups (all P < 0.01). Compared with the WT+IRI group, the positive cell count for cleaved Caspase-3 in liver tissues of mice was significantly increased, whereas the positive cell count forKi-67 and p-Akt was significantly decreased in the KO+IRI group (both P < 0.05).
      Conclusions  β-arrestin-2 can mitigate the liver cell apoptosis and promote the repair of injury after IRI in mice. Moreover, β-arrestin-2 inhibits autophagy by up-regulating the PI3K/Akt signal to alleviate liver IRI in mice.

     

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