Department of Anesthesiology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China.
Am J Nephrol. 2010;32(4):347-55. doi: 10.1159/000319623. Epub 2010 Aug 26.
Living donor liver transplantation (LDLT) patients run the risk of developing acute kidney injury (AKI) and subsequent chronic kidney disease, affecting morbidity and mortality. Sevoflurane has anti-inflammation properties, and renal ischemia/reperfusion under sevoflurane anesthesia resulted in drastic improvements in renal function. Extrahepatic metabolism of sevoflurane has been reported in patients undergoing liver transplantation, and might lead to nephrotoxicity. However, whether sevoflurane anesthesia is safe with regard to renal function in small-size liver transplantation needs further investigation. As neutrophil gelatinase-associated lipocalin (NGAL) is an early predictive biomarker of AKI, we looked at the renal effects of sevoflurane in a rat liver transplantation model using small-for-size grafts to investigate the changes of NGAL level and kidney histology.
Sixty male Sprague-Dawley rats were randomly divided into 2 groups after 50% size liver transplantation. Rats were anesthetized with chloral hydrate or with sevoflurane and subjected to liver transplantation. Twelve rats in each group were used for the survival study and 6 rats were used for the hemodynamic study. Six rats in each group were sacrificed 2 or 24 h after reperfusion. We harvested kidneys and serum for further analysis, including histological and functional parameters; TNF-α, IL-6 and NGAL immunoassay; expressions of myeloperoxidase (MPO) activity; and NF-κB in renal tissues.
Rats in the sevoflurane group had significantly lower Scr 24 h after reperfusion compared with those in the chloral hydrate group. Rats in the sevoflurane group demonstrated significantly reduced NGAL concentrations compared with rats in the chloral hydrate group 2 h after reperfusion. Epithelial necrosis in the chloral hydrate group (3.2 ± 0.8) was greater than that in the sevoflurane group (1.5 ± 1.1; p < 0.05). Sevoflurane anesthesia resulted in significantly lower plasma TNF-α and IL-6 concentrations and reduced MPO concentrations 2 h after reperfusion (p < 0.05). NF-κB protein levels 2 h after reperfusion increased by at least 110% in the chloral hydrate group relative to the sevoflurane group 2 h after reperfusion (p < 0.05). However, the urine inorganic fluoride concentrations increased significantly (p < 0.001) 2 h after reperfusion in the sevoflurane group (6.1 ± 1.5 μmol·l⁻¹) compared with the chloral hydrate group.
Sevoflurane anesthesia can attenuate renal injury and modulate inflammatory cascades in small-size liver transplantation using rat models.
活体供肝移植（LDLT）患者有发生急性肾损伤（AKI）和随后发生慢性肾病的风险，这会影响发病率和死亡率。七氟醚具有抗炎作用，七氟醚麻醉下的肾缺血/再灌注导致肾功能明显改善。有报道称，在接受肝移植的患者中，七氟醚有肝外代谢，可能导致肾毒性。然而，在小体积肝移植中，七氟醚麻醉对肾功能是否安全仍需进一步研究。中性粒细胞明胶酶相关脂质运载蛋白（NGAL）是 AKI 的早期预测生物标志物，我们使用小体积供肝移植模型观察了七氟醚对大鼠的肾脏作用，以研究 NGAL 水平和肾脏组织学的变化。
50%体积肝移植后，60 只雄性 Sprague-Dawley 大鼠随机分为 2 组。大鼠用氯醛或七氟醚麻醉，并进行肝移植。每组 12 只大鼠用于生存研究，6 只大鼠用于血流动力学研究。每组 6 只大鼠在再灌注后 2 或 24 小时处死。我们采集肾脏和血清进行进一步分析，包括组织学和功能参数；TNF-α、IL-6 和 NGAL 免疫测定；髓过氧化物酶（MPO）活性表达；以及肾组织中的 NF-κB。
再灌注后 24 小时，七氟醚组大鼠的 Scr 明显低于氯醛组。再灌注后 2 小时，七氟醚组大鼠的 NGAL 浓度明显低于氯醛组。氯醛组（3.2±0.8）上皮坏死程度大于七氟醚组（1.5±1.1；p<0.05）。再灌注后 2 小时，七氟醚麻醉组血浆 TNF-α 和 IL-6 浓度降低，MPO 浓度降低（p<0.05）。再灌注后 2 小时，氯醛组 NF-κB 蛋白水平至少增加 110%，而七氟醚组 NF-κB 蛋白水平增加（p<0.05）。然而，再灌注后 2 小时，七氟醚组尿液无机氟浓度明显升高（p<0.001）（6.1±1.5μmol·l⁻¹），明显高于氯醛组。
七氟醚麻醉可减轻大鼠小体积肝移植模型的肾损伤，并调节炎症级联反应。
