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甲状腺激素T3减轻小鼠再灌注肾脏炎症反应
王盼梁,何康,张明,张建军*
0
(上海交通大学医学院附属仁济医院肝脏外科,上海200127
*通信作者)
摘要:
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48 h,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。
关键词:  三碘甲状腺原氨酸    再灌注损伤  白细胞介素10  白细胞介素1受体阻滞剂
DOI:10.3724/SP.J.1008.2012.00364
投稿时间:2012-02-13修订日期:2012-03-22
基金项目:上海市科委基金(09410706300).
Thyroid hormone preconditioning alleviates reperfusion-induced renal inflammation in mice
WANG Pan-liang,HE Kang,ZHANG Ming,ZHANG Jian-jun*
(Department of Liver Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai200127, China
*Corresponding author.)
Abstract:
Objective To investigate the influence of thyroid hormone T3 preconditioning on interleukin-10 (IL-10) and interleukin-1 receptor antagonist (IL-1Ra) modulation and neutrophil infiltration after renal shchemia/reperfusion (IR) in mice, so as to study the protective effect of T3 on IR kidney. Methods Totally 120 male C57BL/6 mice were randomly divided into four groups (n=30), namely, control group (sham operation), IR group (only received renal IR), T3+IR group (T3 preconditioning for 48 h before renal IR), and NaOH+IR group (received equivalent 0.1 mol/L NaOH soltuion 48 h before renal IR). The serum creatinine and blood urea nitrogen (BUN) were determined 24 h after reperfusion in each group; renal histological damages were scored using PAS staining; the levels of neutrophil infiltration were evaluated by MPO staining, and IL-10, IL-1Ra mRNA expression was examined by real-time PCR at 1, 3, 6, 12, 24, and 48 h after reperfusion. Results The serum creatinine and BUN levels of T3+IR group were significantly lower than those of IR group 24 h after reperfusion (P<0.05), which was accompanied by lower histological score and significantly less neutrophil infiltration (P<0.05). Real-time PCR results showed that IL-10 and IL-1Ra mRNA expression in T3+IR group was significantly higher than that in the IR group (P<0.05) 12 h after reperfusion, which lasted for 48 h after reperfusion. The above parameters were similar between IR group and NaOH+IR group. onclusion Thyroid hormone T3 preconditioning can alleviate renal IR injury, partly by increasing expression of IL-10 and IL-1Ra and subsequently reducing neutrophil infiltration at the late phase of renal IR.
Key words:  triiodothyronine  kidney  reperfusion injury  interleukin-10  interleukin-1 receptor antagonist