Kim Hyun-Chang, Kim Eugene, Bae Jung Il, Lee Kook Hyun, Jeon Young-Tae, Hwang Jung-Won, Lim Young-Jin, Min Seong-Won, Park Hee-Pyoung
*Department of Anesthesiology and Pain Medicine, Keimyung University Dongsan Hospital, Keimyung University College of Medicine †Department of Anesthesiology and Pain Medicine, Hospital of Catholic University of Daegu, Daegu ‡Department of Anesthesiology and Pain Medicine, Seoul National University Hospital ∥Department of Anesthesiology and Pain Medicine, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul §Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
J Neurosurg Anesthesiol. 2017 Jan;29(1):37-45. doi: 10.1097/ANA.0000000000000331.
The antiapoptotic effects of sevoflurane postconditioning 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.
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.
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.
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.
七氟醚后处理的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-信号转导子和转录激活子（STAT）3通路的磷酸化与抗凋亡相关。在此，我们确定七氟醚后处理的抗凋亡作用是否与大鼠全脑短暂缺血后JAK2-STAT3通路的激活有关。
45只大鼠随机分为5组：假手术组（n = 5）、对照组（缺血10分钟，n = 10）、七氟醚后处理组（缺血10分钟后进行2次七氟醚吸入，n = 10）、AG490组（一种JAK2选择性抑制剂，缺血前腹腔注射40mg/kg，n = 10）以及七氟醚后处理加AG490组（n = 10）。在缺血3天后评估凋亡细胞数量以及JAK2、磷酸化JAK2（P-JAK2）、STAT3、磷酸化STAT3（P-STAT3）、Bcl-2（抗凋亡蛋白）和Bax（促凋亡蛋白）的表达。
七氟醚后处理组的凋亡细胞计数显著低于对照组、AG490组和七氟醚后处理加AG490组。所有5组的JAK2和STAT3水平相当。与对照组、AG490组和七氟醚后处理加AG490组相比，七氟醚后处理组的P-JAK2、P-STAT3和Bcl-2水平较高，而Bax水平较低。
七氟醚后处理通过增加大鼠短暂全脑缺血后的P-JAK和P-STAT表达来减少凋亡，并且AG490逆转了七氟醚后处理的有益抗凋亡作用，提示JAK-STAT通路可能参与七氟醚后处理的抗凋亡机制。
