摘要
目的:舒芬太尼对缺血再灌注(ischemia reperfusion,IR)引起的心肌和肝损伤具有良好的保护作用,但其对肾的保护作用尚不清楚。本研究旨在探讨舒芬太尼是否可以预防IR引起的急性肾损伤(acute kidney injury,AKI),并确定其疗效是否与miR-145介导的自噬有关。方法:40只大鼠随机分为5组(每组8只):假手术组、IR组、舒芬太尼组、舒芬太尼+miR-145抑制剂对照组(舒芬太尼+anti-NC组)和舒芬太尼+miR-145抑制剂组(舒芬太尼+antimiR-145组)。除假手术组外,其余组均建立了由IR诱导的大鼠AKI模型。舒芬太尼组、舒芬太尼+anti-NC组和舒芬太尼+anti-miR-145组在IR处理前30 min通过股静脉注射舒芬太尼(剂量为1μg/kg),后两组大鼠在舒芬太尼预处理前通过尾静脉注射miR-145抑制剂对照或anti-miR-145(剂量为80 mg/kg)。评估大鼠肾的结构和功能,并测量自噬相关蛋白的蛋白水平、氧化应激水平和细胞凋亡水平。结果:与IR组相比,舒芬太尼组改善了肾结构和功能,并且血尿素氮(blood urea nitrogen,BUN)、肌酐(creatinine,Cr)、尿肾损伤分子1(kidney injury molecule 1,KIM-1)、中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase related lipid transporter,NGAL)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素(interleukin,IL)-1β、IL-6和ROS水平均显著降低(均P<0.05)。此外,与IR组相比,舒芬太尼组肾组织肌球蛋白样BCL2结合蛋白(coiled-coil, myosin-like BCL2 interacting protein,Beclin-1)和微管相关蛋白1轻链3(microtubule-associated protein 1 light chain 3,LC3)水平均显著增加(均P<0.05),并且肾组织中的细胞凋亡显著减少(P<0.05)。与舒芬太尼+anti-NC组相比,舒芬太尼+anti-miR-145组BUN、Cr、KIM-1、NGAL、TNF-α、IL-1β、IL-6和ROS水平均显著增加(均P<0.05),肾组织Beclin-1和LC3水平均显著降低(均P<0.05),并且肾组织中的细胞凋亡显著增加(P<0.05)。结论:舒芬太尼可预防IR引起的AKI,其作用机制与上调miR-145介导的自噬有关。
Objective: Sufentanil has a good protective effect on myocardial and liver injury caused by ischemia reperfusion(IR), but its protective effect on kidney is still unclear. This study aims to investigate whether sufentanil can prevent IR-induced acute kidney injury(AKI) and to determine whether its efficacy is related to miR-145-mediated autophagy.Methods: A total of 40 rats were randomly divided into 5 groups(n=8 in each group): A sham group, an IR group, a sufentanil group, a sufentanil+miR-145 inhibitor control group(an anti-NC group) and a sufentanil+miR-145 inhibitor group(an anti-miR-145 group). Except for the sham group, the other groups established a rat AKI model induced by IR. The sufentanil group, the sufentanil+anti-NC group, and the sufentanil+anti-miR-145 were injected with sufentanil(1 μg/kg) through femoral vein 30 min before ischemia. The sufentanil+anti-NC group and the sufentanil+anti-miR-145 group were injected with miR-145 inhibitor control or anti-miR-145(80 mg/kg) through the tail vein before sufentanil pretreatment. The structure and function of kidneys harvested from the rats were evaluated, and the protein levels of autophagy-related proteins, oxidative stress levels, and apoptosis levels were measured.Results: Compared with the IR group, the renal structure and function were improved in the sufentanil group. The levels of blood urea nitrogen(BUN), creatinine(Cr), urinary kidney injury molecule 1(KIM-1), neutrophil gelatinase related lipid transporter(NGAL), tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, IL-6 and ROS were significantly decreased(all P<0.05). In addition, compared with the IR group, the levels of Beclin-1 and LC3 in renal tissues in the sufentanil group were significantly increased(both P<0.05), and the apoptosis in renal tissues was significantly reduced(P<0.05). Compared with the sufentanil+anti-NC group, the levels of BUN, Cr, KIM-1, NGAL, TNF-α, IL-1β, IL-6 and ROS in the sufentanil+anti-miR-145 group were significantly increased(all P<0.05), the levels of Beclin-1 and LC3 in renal tissues were significantly decreased(both P<0.05), and the apoptosis in renal tissues was significantly increased(P<0.05).Conclusion: Sufentanil can prevent the AKI induced by IR, which is related to the upregulation of miR-145-mediated autophagy.
作者
路艳
朴宗方
李建玲
李玲
李汝泓
LU Yan;PIAO Zongfang;LI Jianling;LI Ling;LI Ruhong(Department of Anesthesiology,Affiliated Hospital of Chengde Medical College,Chengde Hebei 067000;Department of Laboratory,Affiliated Hospital of Chengde Medical College,Chengde Hebei 067000,China)
出处
《中南大学学报（医学版）》
CAS
CSCD
北大核心
2022年第10期1315-1323,共9页
Journal of Central South University ：Medical Science
基金
河北省医学科研计划项目(20200430)
承德市科学技术研究与发展计划项目(202006A041)。
