七氟醚调控Nrf2通路减轻大鼠肾缺血再灌注损伤  

Sevoflurane Attenuates Renal Ischemia-reperfusion Injury in Rats by Regulating Nrf2 Signaling Pathway

作　　者：刘义鑫[1] 张帮健[1] 刘鑫[1] 蒋燕[1] 杜学柯[2] LIU Yixin;ZHANG Bangjian;LIU Xin;JIANG Yan;DU Xueke(Department of Anesthesiology, Panzhihua Central Hospital,Panzhihua, Sichuan,617067,China;Department of Anesthesiology, Cancer Hospital, Guangxi Medical University, Nanning, 530000,China)

机构地区：[1]攀枝花市中心医院麻醉科,四川省攀枝花市617067 [2]广西医科大学肿瘤医院麻醉科,南宁市530000

出　　处：《医学分子生物学杂志》2019年第4期361-366,372,共7页Journal of Medical Molecular Biology

基　　金：广西自然科学基金(No.2018GXNSFAA138007).

摘　　要：目的探究七氟醚调控NW2通路,减轻大鼠肾缺血再灌注损伤的作用机制。方法大鼠通过切除右肾并夹闭左肾动脉45min后再灌注制备肾缺血再灌注模型,并经过七氟醚、ML385处理。检测血清肌酐和尿素氮含量,HE染色检测肾脏组织病理变化,TUNEL染色检测肾脏细胞凋亡,试剂盒检测超氧化物歧化酶(superoxide dismutase,SOD)和丙二醛(malondialdehyde,MDA)含量,ELISA检测肿瘤坏死因子(tumor necrosis factor-α,TNF-α)、白细胞介素1β(interleukin-1β,IL-1β)、IL-6的含量,蛋白印迹检测活化半胱天冬酶3(cleave caspase-3,cl-CASP3)、核因子E2相关因子2(nuclear factor-E2-related factor2,Nrf2)、血红素氧化酶1(heme oxygenase1,HO-1)蛋白表达。结果与Control组比较,IR组血清肌酐和尿素氮含量升高,肾脏组织发生明显病理变化,肾脏细胞凋亡增多,氧化应激水平升高,炎性细胞因子含量升高,cl-CASP3、Nrf2、HO-1蛋白表达升高;经过七氟醚处理后,由缺血再灌注引起的个指标变化均得到明显缓解,Nrf-2/HO-1通路激活;通过Nrf2抑制剂ML385处理之后,七氟醚的治疗效果受到明显抑制。结论七氟醚可减轻大鼠肾缺血再灌注损伤,其作用机制与激活Nrf2信号通路有关。Objective To investigate the effect and mechanism of sevoflurane on attenuating renal ischemia-reperfusion injury in rats by regulating Nrf2 signaling pathway. Methods Rats received right nephrectomy. And then renal ischemia reperfusion was induced by clamping the left renal pedicle for 45 min. Each group was treated with sevoflurane, ML385. Serum creatinine (SCr) and blood urea nitrogen (BUN) were detected. HE stain was used for observing the morphological changes in renal tissues. Cell apoptosis was detected by TUNEL method. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by kits. ELISA was used for determining the levels of tumor necrosis factor-α(TNF-α), interleukin-1 P (IL-1 P) and IL-6, the protein expression levels of cleave caspase-3 (cl-CASP3), nuclear factor-E2 -related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) were detected by Western blotting. Results Compared with control group, in IR group, the serum creatinine and blood urea nitrogen were increased, significant morphological changes were observed in renal tissues, cell apoptosis rate was increased, oxidative stress was enhanced, concentrations of inflammatory cytokines were increased, protein expression levels of cl-CASP3 , Nrf2 and HO-1 were increased. After sevoflurane treatment, changes in all indexes caused by ischemia.Teperfusion were alleviated, and Nrf-2/HO-1 pathway was activated. After treatment with Nrf2 inhibitor ML385 , the therapeutic effect of sevoflurane was significantly inhibited. Conclusion Sevoflurane can attenuate renal ischemia reperfusion injury in rats, and its mechanism may be related to the activation of Nrf2 signaling pathway.

关 键 词：肾缺血再灌注 七氟醚 NRF2 大鼠 

分 类 号：R692.9[医药卫生—泌尿科学]