Isoflurane is a widely used inhalational anesthetic with a potent anesthetic effect, rapid onset, and quick elimination[1]. Isoflurane plays an important therapeutic role in cerebral ischemia-reperfusion injury by regulating the production of vascular endothelial growth factor (VEGF) and CD34 via the sonic hedgehog (Shh)/Gli signaling pathway[2]. Isoflurane inhibits electron transfer in respiratory complex I, with concerted downstream effects on membrane potential, ATP availability, and reactive oxygen species (ROS) flux[3]. After 2h of Isoflurane exposure, the human ovarian epithelial carcinoma cell line SK-OV3 and the non-small-cell lung carcinoma (NSCLC) lines A549 and H1299 all exhibited significantly enhanced proliferation and migration[4-5]. In C57/BL/6J mice, a 2h inhalation of 1.4% Isoflurane produced a marked increase in Bax mRNA and protein expression (protein rose from 100% to 170%) and a concurrent decrease in Bcl-2 mRNA and protein expression (protein fell from 100% to 61%) in neurons[6]. Compared with the cerebral ischemia–reperfusion (I/R) injury group, rats inhaling 1.5% or 3.0% Isoflurane for 60min showed markedly lower neurobehavioral deficit scores and smaller infarct volumes[7].
References:
[1] Saha P, Das A, Chatterjee N, et al. Impact of anesthetics on oncogenic signaling network: a review on propofol and isoflurane. Fundam Clin Pharmacol. 2022;36(1):49-71.
[2] Chen SJ, Yuan XQ, Xue Q, et al. Current research progress of isoflurane in cerebral ischemia/reperfusion injury: a narrative review. Med Gas Res. 2022;12(3):73-76.
[3] Rodriguez E, Peng B, Lane N. Anaesthetics disrupt complex I-linked respiration and reverse the ATP synthase. Biochim Biophys Acta Bioenerg. 2025;1866(1):149511.
[4] Iwasaki M, Zhao H, Jaffer T, et al. Volatile anaesthetics enhance the metastasis related cellular signalling including CXCR2 of ovarian cancer cells. Oncotarget. 2016;7(18):26042-26056.
[5] Zhang W, Shao X. Isoflurane Promotes Non-Small Cell Lung Cancer Malignancy by Activating the Akt-Mammalian Target of Rapamycin (mTOR) Signaling Pathway. Med Sci Monit. 2016;22:4644-4650.
[6] Zhang Y, Dong Y, Wu X, et al. The mitochondrial pathway of anesthetic isoflurane-induced apoptosis. J Biol Chem. 2010;285(6):4025-4037.
[7] Wang S, Yin J, Ge M, et al. Transforming growth-beta 1 contributes to isoflurane postconditioning against cerebral ischemia-reperfusion injury by regulating the c-Jun N-terminal kinase signaling pathway. Biomed Pharmacother. 2016;78:280-290.
Isoflurane是一种广泛应用的吸入麻醉药，具有强效麻醉、起效迅速和清除快的特点[1]。在脑缺血-再灌注损伤中，Isoflurane通过调控sonic hedgehog (Shh)/Gli信号通路，调节血管内皮生长因子（VEGF）和CD34的产生，发挥重要治疗作用[2]。Isoflurane可抑制呼吸链复合体I的电子传递，进而影响膜电位、ATP供应和活性氧（ROS）通量[3]。人卵巢上皮癌细胞系SK-OV3以及非小细胞肺癌细胞系A549和H1299在暴露于Isoflurane 2小时后，增殖与迁移能力均显著增强[4-5]。在C57/BL/6J小鼠中，吸入1.4%的Isoflurane 2小时可使神经元Bax mRNA及蛋白表达显著升高（蛋白水平由100%升至170%），同时Bcl-2 mRNA及蛋白表达显著降低（蛋白水平由100%降至61%）[6]。与单纯脑缺血-再灌注（I/R）损伤组相比，吸入1.5%或3.0%的Isoflurane 60分钟的大鼠神经行为学评分明显降低，脑梗死体积显著缩小[7]。