Department of Anesthesiology and Pain Medicine, Graduate School of Medicine, Nippon Medical School, Tokyo 1138602, Japan.
Int J Mol Med. 2020 Apr;45(4):1141-1149. doi: 10.3892/ijmm.2020.4477. Epub 2020 Jan 27.
The kidneys are prone to developing ischemia reperfusion injury (IRI) following certain renal surgeries and cardiovascular surgeries requiring cardiac arrest. Sevoflurane and ischemic preconditioning reportedly alleviate IRI, which is mediated via microRNAs. The present study compared anesthetic preconditioning (APC) and ischemic preconditioning (IPC) on microRNAs, which promote cell‑survival pathways in rats in a randomized controlled study. After undergoing right nephrectomy under general anesthesia, male Wistar rats (336±24 g) and were divided into four groups (IRI, APC, IPC and sham; n=7 each). The IRI group underwent 45 min clamping of the left renal vasculature, followed by 4 h of reperfusion. APC involved exposure to one minimum alveolar concentration sevoflurane for 15 min. IPC included three cycles of two‑min clamping and five‑min reperfusion. Blood and renal biopsy samples were assessed postoperatively to measure serum creatinine and to analyze renal microRNA (miR) expression using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) testing and their target pathways with Ingenuity Pathway Analysis™. The present study found that serum creatinine values in APC (0.71±0.08 mg/dl) and IPC (0.73±0.1 mg/dl) groups were lower than in the IRI group (0.96±0.13 mg/dl; P<0.05), indicating amelioration of IRI by APC and IPC. RT‑qPCR followed by pathway analysis indicated that APC and IPC affect 'protein kinase B (Akt)'. APC promoted miR‑17‑3p and suppressed miR‑27a. IPC promoted miR‑19a. All the miRs were predicted to regulate phosphorylated Akt, which promotes cell‑protection. Western blot analysis showed that expression of phosphorylated Akt increased and phosphatase and tensin homologue deleted from chromosome 10 (PTEN) decreased following APC and IPC. The present study concluded that APC and IPC affect different miRs, although they are estimated to similarly promote the PTEN/phosphoinositide 3‑kinase/Akt signaling pathway, resulting in reno‑protection.
肾脏在某些肾脏手术和需要心脏骤停的心血管手术后容易发生缺血再灌注损伤(IRI)。据报道,七氟醚和缺血预处理可减轻 IRI,其通过 microRNAs 介导。本研究在一项随机对照研究中比较了麻醉预处理(APC)和缺血预处理(IPC)对促进大鼠细胞存活途径的 microRNAs 的影响。雄性 Wistar 大鼠(336±24g)在全身麻醉下接受右肾切除术,然后分为四组(IRI、APC、IPC 和假手术;每组 7 只)。IRI 组左肾血管夹闭 45min,再灌注 4h。APC 组吸入 1 个最低肺泡浓度七氟醚 15min。IPC 组包括 2min 夹闭和 5min 再灌注 3 个循环。术后评估血样和肾活检样本以测量血清肌酐,并使用逆转录-定量聚合酶链反应(RT-qPCR)检测和 Ingenuity Pathway Analysis™ 分析肾 microRNA(miR)表达及其靶途径。本研究发现,APC(0.71±0.08mg/dl)和 IPC(0.73±0.1mg/dl)组的血清肌酐值低于 IRI 组(0.96±0.13mg/dl;P<0.05),表明 APC 和 IPC 改善了 IRI。RT-qPCR 后通路分析表明,APC 和 IPC 影响“蛋白激酶 B(Akt)”。APC 促进 miR-17-3p,抑制 miR-27a。IPC 促进 miR-19a。所有 miR 均被预测可调节磷酸化 Akt,促进细胞保护。Western blot 分析表明,APC 和 IPC 后磷酸化 Akt 表达增加,第 10 号染色体缺失的磷酸酶和张力蛋白同源物(PTEN)减少。本研究得出结论,APC 和 IPC 影响不同的 miR,尽管它们估计可类似地促进 PTEN/磷酸肌醇 3-激酶/Akt 信号通路,从而实现肾保护。