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目的观察甲状腺激素T3预处理对小鼠缺血-再灌注(IR)肾脏白介素-10(IL-10)、内源性白介素-1受体阻滞剂(IL-1Ra)表达的调控及其对中性粒细胞浸润的影响,探讨T3对IR肾脏的保护作用及可能的机制。方法120只雄性C57BL/6小鼠随机分为4组(n=30):正常对照组(假手术)、单纯IR组(仅行肾脏IR)、T3+IR组(肾脏IR前48 h行T3预处理)、NaOH+IR组(肾脏IR前48 h注射等量0.1 mol/L NaOH),建立肾脏IR模型。各组于再灌注后24 h取血标本进行肾功能检测(肌酐、尿素氮);取肾脏标本采用PAS染色评估肾脏组织形态学改变,髓过氧化物酶(MPO)染色评估中性粒细胞浸润情况;real-time PCR检测肾脏再灌注后1、3、6、12、24、48 h的IL-10、IL-1Ra mRNA的表达。结果再灌注后24 h T3+IR组血肌酐、尿素氮水平较单纯IR组降低(P<0.05)、肾脏损伤程度轻(P<0.05);MPO染色示T3+IR组中性粒细胞浸润较单纯IR组明显减少(P<0.05)。再灌注后12 h,T3+IR组IL-10、IL-1Ra mRNA表达高于单纯IR组,并持续至再灌注后48h,差异有统计学意义(P<0.05)。单纯IR组和NaOH+IR组在上述各项指标的变化上无明显差异。结论 T3能在肾脏再灌注的晚期阶段发挥作用,促进IL-10、IL-1Ra的表达,减轻中性粒细胞浸润所产生的炎症反应,改善肾功能。
Objective To observe the effect of thyroid hormone T3 pretreatment on the expression of interleukin-10 (IL-10) and endogenous interleukin-1 receptor blocker (IL-1Ra) in the kidney of ischemia-reperfusion Neutrophil infiltration, to explore the protective effect of T3 on IR kidney and its possible mechanism. Methods 120 male C57BL / 6 mice were randomly divided into 4 groups (n = 30): normal control group (sham operation), simple IR group (renal IR only), T3 + IR group Pretreatment) and NaOH + IR group (the same amount of 0.1 mol / L NaOH was injected 48h before renal IR). Renal function tests (creatinine and urea nitrogen) were taken at 24 h after reperfusion in each group. Kidney specimens were examined for renal histological changes by PAS staining. Myeloperoxidase (MPO) staining was used to evaluate neutrophil infiltration The expression of IL-10 and IL-1Ra mRNA was detected by real-time PCR at 1, 3, 6, 12, 24 and 48 h after renal reperfusion. Results The levels of serum creatinine and urea nitrogen in T3 + IR group were significantly lower than those in IR group (P <0.05) at 24 h after reperfusion, and the severity of renal damage was lighter (P <0.05). The MPO staining showed that the infiltration of neutrophils in T3 + IR group IR group decreased significantly (P <0.05). At 12 h after reperfusion, the expression of IL-10 and IL-1Ra mRNA in T3 + IR group was significantly higher than that in IR group and continued to 48h after reperfusion (P <0.05). The IR group and NaOH + IR group had no significant difference in the above indexes. Conclusion T3 can play a role in the later stage of renal reperfusion, promote the expression of IL-10 and IL-1Ra, relieve the inflammatory reaction induced by neutrophil infiltration and improve renal function.