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目的 探讨核因子 κB (NF κB)诱捕物寡聚核苷酸 (ODN)对急性缺血性肾损伤的保护作用。方法 采用肾动脉夹闭法制备大鼠缺血性急性肾衰竭 (iARF)模型 ,应用鱼精蛋白 脂质体法经肾动脉转染NF κB诱捕物ODN进行治疗。 2 4只大鼠被分成 4组 :假手术组 ,急性肾衰竭组 (iARF组 ) ,NF κB诱捕物ODN治疗组 (NF κB组 )和错配物ODN处理组。应用生化和组织学指标检测肾脏损伤的程度 ;凝胶电泳迟滞分析检测肾组织NF κB/DNA结合活性 ;免疫组化和RT PCR技术分别检测单核 巨噬细胞浸润 (M/MΦ)和单核细胞趋化蛋白 1(MCP 1)的表达。结果 经鱼精蛋白 脂质体法转染NF κB诱捕物ODN 12h后 ,ODN主要分布在肾小管上皮。与假手术组比较 ,iARF组血清Cr、BUN水平分别增加 10倍和 5倍 ( 2 5 6 μmol/L± 84 μmol/Lvs 2 5 μmol/L± 5 μmol/L和 4 3 4 7μmol/L± 13 4 8μmol/Lvs8 4 5mmol/L± 1 0 7mmol/L ,Ps<0 0 1) ;肾小管损伤评分明显升高 ( 3 6 3± 0 15vs 0 0 0± 0 0 0 ,P <0 0 1) ;NF κB /DNA结合活性明显增加 [中位数 (M) :1 75vs0 15 ,P <0 0 5 ];M/MΦ以及MCP 1的表达水平明显上升。与iARF组比较 ,NF κB组经诱捕物ODN治疗后 ,血清Cr水平下降 70 % ( 79μmol/L± 2 1μmol/Lvs 2 5 6 μmol/L± 84 5
Objective To investigate the protective effect of nuclear factor κB decoy oligodeoxynucleotide (ODN) on acute ischemic renal injury. Methods Rat model of acute renal failure (iARF) was established by clipping the renal artery. The animal model of amniotic fluid translocation of NF - κB decoy ODN was treated with protamine liposome. 24 rats were divided into 4 groups: sham operation group, acute renal failure group (iARF group), NFκB decoy ODN treatment group (NF κB group) and mismatch ODN treatment group. The degree of renal damage was detected by biochemical and histological indexes. The NF-κB / DNA binding activity in renal tissues was detected by gel electrophoresis hysteresis analysis. The expressions of monocyte-macrophage infiltration (M / MΦ) and mononuclear Cell chemotactic protein 1 (MCP 1) expression. Results ODN was mainly distributed in renal tubular epithelial cells after transfection of NFκB decoy ODN by protamine liposome for 12 hours. Compared with the sham-operated group, serum Cr and BUN levels in iARF group increased by 10-fold and 5-fold, respectively (2.56 μmol / L ± 84 μmol / L vs 25 μmol / L ± 5 μmol / L and 4347 μmol / L ± 13 4 8μmol / L vs8 4 5mmol / L ± 1 0 7mmol / L, Ps <0.01); tubule damage score was significantly higher (363 ± 0 15 vs 0 0 0 ± 0 0 0, P 0 01 ); NF κB / DNA binding activity was significantly increased [M (median): 1 75 vs 0 15, P <0 05]; M / MΦ and MCP 1 expression increased significantly. Compared with the iARF group, serum Cr levels decreased by 70% in the NF-κB group after trapping ODN treatment (79 μmol / L ± 2 1 μmol / L vs 256 μmol / L ± 84 5