舒芬太尼调节高迁移率族蛋白1/Toll样受体4/核因子-κB信号通路对脓毒症大鼠急性肾损伤的影响  

Effect of Sufentanil on Acute Kidney Injury in Septic Rats by Regulating High Mobility Group Box 1 Protein/Toll-Like Receptor 4/Nuclear Factor-κB Signaling Pathway

作　　者：何洁[1] 张永洪[1] 宋波 He Jie;Zhang Yonghong;Song Bo(Anesthesiology Department of Mianyang Central Hospital,Mianyang,Sichuan 621000,China)

机构地区：[1]绵阳市中心医院麻醉科,四川绵阳621000

出　　处：《四川医学》2025年第1期49-54,共6页Sichuan Medical Journal

摘　　要：目的探索舒芬太尼(SUF)对脓毒症大鼠急性肾损伤(AKI)的影响以及对高迁移率族蛋白1(HMGB1)/Toll样受体4(TLR4)/核因子-κB(NF-κB)信号通路的调节机制。方法将60只大鼠随机分为假手术组、模型组、阳性药物组(亚胺培南/西司他丁)、SUF低剂量组、SUF高剂量组、SUF高+HMGB1组,每组10只。检测大鼠血清中肾功能标志物肌酐(Cr)、尿素氮(BUN)的水平;HE染色观察大鼠肾脏的病理变化;TUNEL染色检测大鼠肾脏细胞凋亡情况;酶联免疫吸附试验检测血清中促炎因子肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-1β、IL-6的水平;Western Blot检测大鼠肾脏中通路蛋白HMGB1、TLR4、NF-κB p65、p-NF-κB p65的表达。结果与假手术组相比,模型组大鼠血清中肾功能指标Cr、BUN水平,促炎因子TNF-α、IL-1β、IL-6水平,细胞凋亡率,HMGB1、TLR4表达及p-NF-κB p65/NF-κB p65比值均升高(P<0.05)。与模型组相比,阳性药物和SUF低、高剂量组大鼠肾功能指标Cr、BUN水平,促炎因子TNF-α、IL-1β、IL-6的水平,细胞凋亡率,HMGB1、TLR4表达及p-NF-κB p65/NF-κB p65比值均显著降低(P<0.05)。HMGB1过表达逆转了SUF对信号通路、炎症和氧化应激损伤及肾功能障碍的抑制作用(P<0.05)。结论SUF可以减轻脓毒症大鼠AKI,其作用机制可能与HMGB1/TLR4/NF-κB信号通路被抑制有关。Objective To investigate the effect of sufentanil(SUF)on acute kidney injury(AKI)in septic rats and the mechanism on high mobility group box 1 protein(HMGB1)/toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)signal pathway regulated by SUF.Methods A total of 60 rats were randomly divided into sham operation group,model group,positive drug group(imipenem/cilastatin),SUF low dose group,SUF high dose group,and SUF high dose+HMGB1 group,with 10 rats in each group.The levels of creatinine(Cr)and blood urea nitrogen(BUN)in serum of rats were detected;HE staining was used to observe the pathological changes of kidney;TUNEL staining was used to detect the apoptosis of renal cells in rats;the levels of pro-inflammatory factor tumor necrosis factorα(TNF-α),interleukin(IL)-1βand IL-6 in serum were detected by enzyme linked immunosorbent assay;and Western blot was used to detect the expression of pathway proteins HMGB1,TLR4,NF-κB p65,p-NF-κB p65 in rat kidney.Results Compared with the sham operation group,the levels of serum renal function index Cr and BUN,the levels of pro-inflammatory factors TNF-α,IL-1β,IL-6,apoptosis rate,the expression of HMGB1,TLR4,and the ratio of p-NF-κB p65/NF-κB p65 in the model group were increased(P<0.05).Compared with the model group,the levels of renal function index Cr and BUN,the levels of pro-inflammatory factors TNF-α,IL-1β,IL-6,apoptosis rate,the expression of HMGB1,TLR4,and the ratio of p-NF-κB p65/NF-κB p65 in the the positive drug and SUF low and high dose groups were decreased significantly(P<0.05).Overexpression of HMGB1 reversed the inhibitory effects of SUF on signal pathway,inflammatory and oxidative stress injury and renal dysfunction(P<0.05).Conclusion SUF can alleviate AKI in septic rats,and the mechanism may be related to the inhibition of HMGB1/TLR4/NF-κB signaling pathway.

关 键 词：舒芬太尼 HMGB1/TLR4/NF-κB 脓毒症 急性肾损伤 

分 类 号：R692.5[医药卫生—泌尿科学] R-332[医药卫生—外科学]