NLRP3炎性体在缺血-再灌注急性肾损伤大鼠肾组织的表达及地塞米松干预对其影响  

Expression of NLRP3 inflammasome in renal tissue of rats with acute kidney injury induced by ischemia-reperfusion and intervention of dexamethasone

作　　者：玄先法 王玉新 张以勤 颜建华 周丽娜 武挺 张丝雨 赵本华[2] Xuan Xian-fa;Wang Yu-xin;Zhang Yi-qin;Yan Jian-hua;Zhou Li-na;Wu Ting;Zhang Si-yu;Zhao Ben-hua(Department of Nephrology,the Second Affiliated Hospital of Xiamen Medical College (the Second Hospital of Xiamen),Xiamen 361021,China)

机构地区：[1]厦门医学院附属第二医院(厦门市第二医院)肾内科,福建厦门361021 [2]厦门大学公共卫生学院,福建厦门361102

出　　处：《中国急救医学》2019年第6期591-596,共6页Chinese Journal of Critical Care Medicine

基　　金：厦门市科技局2016科技惠民项目(3502Z20164060).

摘　　要：目的研究缺血-再灌注急性肾损伤(AKI)大鼠肾组织中Nod样受体蛋白3(NLRP3)炎性体的表达以及地塞米松干预对其影响。方法选取发育正常的SD雄性大鼠21只,将实验大鼠平均分为三组并进行大鼠模型构造,分别为缺血-再灌注组(A组)、假手术组(B组)及地塞米松+缺血-再灌注组(C组),对比各组之间血肌酐、尿素氮变化及NLRP3表达的差异情况,分析地塞米松干预治疗对大鼠体内NLRP3炎性体含量的影响。采用Western blot检测大鼠肾组织NLRP3蛋白的表达情况,应用ELISA检测大鼠肾组织中白细胞介素-1β(IL-1β)以及白细胞介素-18(IL-18)的水平,采取免疫组化检测各组间肾脏NLRP3表达情况,病理学检查各组大鼠的肾小管间质损伤情况。结果 A组大鼠血肌酐、尿素氮水平、NLRP3炎性体蛋白表达以及IL-1β、IL-18水平明显高于B组大鼠[分别为(89.5±10.8)μmol/L vs.(22.3±3.1)μmol/L,(23.1±5.3)mmol/L vs.(4.8±0.7) mmol/L,(0.39±0.11) vs.(0.08±0.01),(21.7±5.6)pg/mL vs.(5.7±1.9) pg/mL,(42.5±6.7) pg/mL vs.(11.4±2.3)pg/mL],差异均有统计学意义(P<0.05);C组大鼠血肌酐、尿素氮水平及肾组织NLRP3表达明显低于A组大鼠[(53.4±8.3)μmol/L vs.(89.5±10.8)μmol/L,(9.6±2.9)mmol/L vs.(23.1±5.3)mmol/L,(0.21±0.07)vs.(0.39±0.11),P<0.05];免疫组化显示,缺血-再灌注组大鼠肾小管上皮细胞NLRP3的表达显著升高;病理学检查显示,缺血-再灌注组大鼠肾小管间质损伤较重。结论缺血-再灌注AKI会伴随血肌酐水平及NLRP3炎性体、IL-1β、IL-18的快速增高以及肾组织NLRP3表达增强,地塞米松干预能够减少肾组织NLRP3炎性体含量,减轻肾组织的损伤程度。Objective To investigate the expression of NLRP3 inflammasome and the effect of dexamethasone in renal tissue of rats with acute kidney injury induced by ischemia-reperfusion.Methods Twenty-one normal male SD rats were randomly divided into three groups,respectively ischemia-reperfusion group (Group A),sham operation group (Group B) and dexamethasone + ischemia reperfusion group (Group C).The differences of serum creatinine,urea nitrogen and NLRP3 expression among the groups were compared.The effect of dexamethasone on the content of NLRP3 inflammatory body in rats was analyzed.The expression of NLRP3 protein in rat renal tissue was detected by Western blot;the levels of IL-1β and IL-18 in rat kidney were detected by ELISA;the expression of NLRP3 in kidney was detected by immunohistochemistry,renal tubulointerstitial injury was detected by pathological examination.Results The levels of serum creatinine,urea nitrogen,IL-1β,IL-18 and NLRP3 inilammasome protein in group A rats were significantly higher than those in group B [(89.5 ± 10.8)μmol/L &(22.3 ± 3.1)|xmol/L,(23.1 ±5.3) mmol/L &(4.8 ± 0.7) mmol/L,(0.39 ± 0.11)&(0.08 ±0.01),(21.7 ±5.6) pg/mL &(5.7 ± 1.9) pg/mL,(42.5 ±6.7) pg/mL &(11.4 ± 2.3) pg/mL;P <0.05 ].The levels of serum creatinine,urea nitrogen,IL-1β,IL-18 and NLRP3 inflammasome protein in group C were significantly lower than those in group A [(53.4 ± 8.3)μmol/L &(89.5 ±10.8)μmol/L,(9.6±2.9) mmol/L &(23.1 ±5.3) mmol/L,(0.21 ±0.07)&(0.39 ± 0.11);P < 0.05 ].Immunohistochemistry showed that the expression of NLRP3 in renal tubular epithelial cells in rats with acute kidney injury after ischemia-reperfusion was significantly increased.Pathological examination showed that the tubulointerstitial injury was severe in the ischemia-reperfusion group.Conclusion Acute kidney injury after ischemia-reperfusion is associated w让h an increase in serum creatinine,IL-1β,IL-18 and NLRP3 inflammasome levels and NLRP3 expression of renal tissue.Intervention with dexamethasone can reduce the NLRP3 i

关 键 词：NLRP3炎性体 缺血-再灌注 急性肾损伤(AKI) 地塞米松 

分 类 号：R692[医药卫生—泌尿科学]