Sevoflurane Postconditioning Reduces Apoptosis by Activating the JAK-STAT Pathway After Transient Global Cerebral Ischemia in Rats
Sevoflurane Postconditioning Reduces Apoptosis by Activating the JAK-STAT Pathway After Transient Global Cerebral Ischemia in Rats
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DOI：
10.1097/ana.0000000000000331
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发表时间：
2017-01-01
影响因子：
3.7
通讯作者：
Park, Hee-Pyoung
中科院分区：
文献类型：
--
作者：
Kim, Hyun-Chang;Kim, Eugene;Park, Hee-Pyoung
背景：七氟醚后处理具有抗凋亡作用，对脑缺血再灌注损伤具有神经保护作用。Janus家族酪氨酸激酶（JAK） 2信号转导和转录激活因子（STAT） 3途径的磷酸化与抗细胞凋亡有关。在这里，我们确定了七氟醚后处理的抗凋亡作用是否与大鼠完全性脑缺血后JAK2-STAT3通路的激活有关。材料与方法：将45只大鼠随机分为5组：假手术组（n=5）、对照组（缺血10 min， n=10）、七氟醚后处理组（缺血后吸入七氟醚2次，10 min, n=10）、AG490 （JAK2选择性抑制剂，缺血前腹腔注射40 mg/kg， n=10）、七氟醚后处理+ AG490组（n=10）。观察缺血后3 d凋亡细胞数量及JAK2、磷酸化JAK2 （P-JAK2）、STAT3、磷酸化STAT3 （P-STAT3）、抗凋亡蛋白Bcl-2、促凋亡蛋白Bax的表达。结果：七氟醚后处理组的凋亡细胞计数明显低于对照组、AG490组和七氟醚后处理加AG490组。5组间JAK2和STAT3水平具有可比性。与对照组、AG490组和七氟烷后处理加AG490组相比，七氟烷后处理组P-JAK2、P-STAT3和Bcl-2水平较高，Bax水平较低。结论：七氟醚后处理通过增加大鼠短暂性全脑缺血后P-JAK和P-STAT的表达减少细胞凋亡，而AG490逆转了七氟醚后处理的有益抗凋亡作用，提示JAK-STAT通路可能参与了七氟醚后处理的抗凋亡机制。
Background: The antiapoptotic effects of sevoflurane post-conditioning are responsible for neuroprotection against cerebral ischemia-reperfusion injury. Phosphorylation of the Janus family tyrosine kinases (JAK) 2-signal transducers and activators of transcription (STAT) 3 pathway is linked to antiapoptosis. Here, we determined whether the antiapoptotic effects of sevoflurane postconditioning are associated with activation of the JAK2-STAT3 pathway after global transient cerebral ischemia in rats.Materials and Methods: Forty-five rats were randomly assigned to 5 groups: sham (n=5), control (10 min of ischemia, n=10), sevoflurane postconditioning (2 periods of sevoflurane inhalation after ischemia for 10 min, n=10), AG490 (a JAK2 selective inhibitor, intraperitoneal administration of 40 mg/kg before ischemia, n=10), and sevoflurane postconditioning plus AG490 group (n=10). The number of apoptotic cells as well as the expression of JAK2, phosphorylated JAK2 (P-JAK2), STAT3, phosphorylated STAT3 (P-STAT3), Bcl-2 (antiapoptotic protein), and Bax (proapoptotic protein) were evaluated 3 days after ischemia.Results: The apoptotic cell count was significantly lower in the sevoflurane postconditioning group than in the control, AG490, and sevoflurane postconditioning plus AG490 groups. JAK2 and STAT3 levels were comparable among all 5 groups. P-JAK2, P-STAT3, and Bcl-2 levels were higher and Bax levels were lower in the sevoflurane postconditioning group relative to the control, AG490, and sevoflurane postconditioning plus AG490 groups.Conclusions: Sevoflurane postconditioning reduced apoptosis by increasing P-JAK and P-STAT expression after transient global ischemia in rats, and AG490 reversed the beneficial antiapoptotic effects of sevoflurane postconditioning, suggesting that the JAK-STAT pathway may be involved in the antiapoptotic mechanism of sevoflurane postconditioning.