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

异氟醚通过抑制蛋白激酶、JNK 和 ERK 来保护肾功能免受缺血和再灌注的影响。

• 批准号: 15591639
• 负责人: MOROOKA Hiroaki
• 金额: $ 1.79万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591639/
• 关键词: SAPK; JNK; p38 MAPK; Ischemia-Reperfusion; ERK; isoflurane; 薬理学的プレコンディショニング; 麻酔薬; 腎機能障害; 虚血性再灌流障害; アポトーシス; NfkB; 虚血再潅流障害; NFkB

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.

缺血/再灌注损伤（IRI）是外科手术中的主要问题。异氟烷对心脏和大脑中的IR具有药理学预处理作用，但这是否也发生在肾脏中尚不清楚。在这项研究中，我们测试的假设，异氟醚对IRI在大鼠肾脏的保护作用，并进一步JNK抑制有助于这种保护作用。F组仅行假手术。G组在假手术前吸入1.5%异氟醚。H组和I组通过夹闭肾蒂使左肾缺血40分钟。I组在肾缺血前吸入1.5%异氟醚20 min。分别于缺血再灌注0、5、40、90 min和假手术后40 min取肾，检测JNK活性，H组（缺血组）JNK活性在再灌注后5 min即明显激活，40 min达高峰，并维持较高水平至再灌注后90 min。I组（异氟醚）再灌注后40 ~ 90 min JNK活性显著低于H组。我们的结论是，异氟醚有保护作用，对肾IRI时，缺血前给药，该效果将涉及抑制JNK。

项目成果

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

• DOI: 10.1213/01.ane.0000184044.51749.b8
• 发表时间: 2005-12-01
• 期刊: ANESTHESIA AND ANALGESIA
• 影响因子: 5.7
• 作者: Hashiguchi, H;Morooka, H;Sumikawa, K
• 通讯作者: Sumikawa, K

Effect of cyclooxygenase-2 inhibitor pretreatment on gas exchange after hydrochloric acid aspiration in rats

• DOI: 10.1007/s00540-005-0322-4
• 发表时间: 2005-08
• 期刊: Journal of Anesthesia
• 影响因子: 2.8
• 作者: Y. Terao;Toshiaki Nakamura;H. Morooka;K. Sumikawa

Masanori Matsumoto, et al.: "Isoflurane inhibits NFkB activation in response to simulated ischemia in renal tubular cell line"Anesthesiology. 99. A1545 (2003)

Masanori Matsumoto 等人：“异氟醚抑制肾小管细胞系中模拟缺血反应中的 NFkB 激活”麻醉学。

Effect of Cyclooxygenase-2 inhibitor pretreatment on gas exchange after hydrochloric acid asniration in rats.

环氧合酶 2 抑制剂预处理对大鼠盐酸吸入后气体交换的影响。

• 发表时间: 2005
• 期刊: Journal of Anesthesia 19
• 作者: Yoshiaki Terao;Hiroaki Morooka;et al.
• 通讯作者: et al.

Hideo Hashiguchi, et al.: "Pharmacological preconditioning effect of isoflurane against renal ischemia/reperfusion injure in rats"Anesthesiology. 99. A83 (2003)

Hideo Hashiguchi 等人：“异氟烷对大鼠肾缺血/再灌注损伤的药理预处理作用”麻醉学。