Department of Anesthesiology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China.
J Surg Res. 2012 Dec;178(2):578-85. doi: 10.1016/j.jss.2012.06.007. Epub 2012 Jun 21.
The authors investigated the cardioprotection afforded by postconditioning with intravenous infusion of emulsified isoflurane in a rat model in vivo and determined the role of Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway in such procedure.
Rats were subjected to a 30-min coronary artery occlusion followed by a 120-min reperfusion. Postconditioning was achieved by inhalation of 1 minimum alveolar concentration isoflurane or intravenous infusion of emulsified isoflurane (8% vol/vol) during the last 3 min of coronary artery occlusion and the first 5 min of reperfusion. AG490 was used to inhibit the activity of JAK2. Infarct size was determined by triphenyltetrazolium chloride staining. Expressions of JAK2, STAT1, and STAT3 were measured by Western blot.
Infarct size was significantly reduced from 51.6% ± 7.6% in the control group to 29.8% ± 7.0% in rats postconditioned with inhalation of isoflurane (P < 0.01). A powerful infarct-sparing effect was also induced by postconditioning with intravenous infusion of emulsified isoflurane (33.7% ± 5.6% versus control group, P < 0.01). Pretreatment with AG490 abolished the anti-infarct effects conducted by either inhalation of isoflurane (44.1% ± 7.1% versus control group, P > 0.05) or intravenous infusion of emulsified isoflurane (51.4% ± 6.8% versus control group, P > 0.05). Compared with the control group, postconditioning with inhalation of isoflurane or infusion of emulsified isoflurane remarkably enhanced the expression of phosphorylation of JAK2 Tyr(1007)/Tyr(1008) and STAT3 Tyr(705), but not phosphorylation of STAT1 Tyr(701).
Postconditioning with intravenous infusion of emulsified isoflurane induces powerful cardioprotection, which is mediated, at least in part, by activating JAK-STAT pathway.
作者研究了静脉输注乳化异氟醚在体内大鼠模型中的后处理保护作用，并确定了 Janus 激酶（JAK）-信号转导和转录激活因子（STAT）通路在此过程中的作用。
大鼠接受 30 分钟冠状动脉闭塞，然后再进行 120 分钟再灌注。后处理通过在冠状动脉闭塞的最后 3 分钟和再灌注的前 5 分钟内吸入 1 最小肺泡浓度异氟醚或静脉输注乳化异氟醚（8%体积/体积）来实现。AG490 用于抑制 JAK2 的活性。通过氯化三苯基四氮唑染色确定梗死面积。通过 Western blot 测量 JAK2、STAT1 和 STAT3 的表达。
与对照组（51.6%±7.6%）相比，吸入异氟醚后处理可显著减少梗死面积（29.8%±7.0%，P<0.01）。静脉输注乳化异氟醚后处理也可诱导强大的梗死保护作用（33.7%±5.6%与对照组相比，P<0.01）。AG490 预处理可消除吸入异氟醚（44.1%±7.1%与对照组相比，P>0.05）或静脉输注乳化异氟醚（51.4%±6.8%与对照组相比，P>0.05）引起的抗梗死作用。与对照组相比，吸入异氟醚或输注乳化异氟醚后处理可显著增强 JAK2 Tyr（1007）/Tyr（1008）和 STAT3 Tyr（705）的磷酸化表达，但不增强 STAT1 Tyr（701）的磷酸化表达。
静脉输注乳化异氟醚后处理可诱导强大的心脏保护作用，至少部分通过激活 JAK-STAT 通路介导。
