Isoflurane protects renal function against ischemia and reperfusion through inhibition of protein kinases, JNK and ERK.

缺血再灌注损伤（Ischemia/reperfusion injury， IRI）是外科手术中的一个主要问题。异氟醚在心脏和大脑中具有抗IR的药理预处理作用，但这种作用是否也发生在肾脏中尚不清楚。在本研究中，我们验证了异氟醚对大鼠肾脏IRI具有保护作用的假设，并进一步证明了JNK抑制有助于这种保护作用。动物被随机分为四组。F组仅行假手术。G组假手术前使用1.5%异氟醚。H组和I组左肾缺血40 min，夹持肾蒂。组1在肾缺血前给予1.5%异氟醚治疗20 min。在开始再灌注后0、5、40和90分钟收获缺血肾，在假手术后40分钟收获假肾，测量JNK活性。H组（仅缺血）JNK早在再灌注开始后5分钟就明显激活，在40分钟达到峰值，并在再灌注开始后90分钟保持较高水平。再灌注后40 ~ 90 min，异氟醚组JNK活性明显低于H组。我们得出结论，异氟醚在缺血前给药对肾脏IRI具有保护作用，并且这种作用可能涉及抑制JNK。

Ischemia/reperfusion injury (IRI) is a major problem in the surgery. Isoflurane has a pharmacological preconditioning effect against IR in the heart and brain, but whether this also occurs in the kidney is still unclear. In this study, we tested the hypothesis that isoflurane had a protective effect against IRI in the rat kidney, and further that JNK inhibition contributed this protective effect.Animals were randomly divided into four groups. Group F underwent sham surgery only. Group G received 1.5% isoflurane before sham surgery. Groups H and I were subjected to 40-min left renal ischemia by clamping the renal pedicles. Group I received 1.5% isoflurane for 20 min before renal ischemia. Ischemic kidneys were harvested at 0, 5, 40 and 90 min after starting reperfusion, and sham kidneys were harvested at 40 min after sham surgery, for measurement of JNK activities.JNK was markedly activated as early as 5 min after starting reperfusion, with a peak at 40 min, and remained at a relatively high level until 90 min after starting reperfusion in group H (ischemia only). The activity of JNK in group I (with isoflurane) was significantly lower than in group H from 40 to 90 min after starting reperfusion. We conclude that isoflurane has a protective effect against renal IRI when administered before ischemia and that the effect would involve the inhibition of JNK.