核因子-κB反义核酸对肾病大鼠肾小球硬化细胞凋亡的干预

Intervention of antisense oligonucleotide targeting NF-кB to apoptosis in glomerulosclerosis

目的探讨核转录因子κB(NF-κB)反义核酸对阿霉素肾病大鼠肾小球细胞凋亡的干预作用。方法SD雄性大鼠分成A组(假手术组)、B组(硬化组)、C组(正义核酸组)、D组(无义核酸组)及E组(反义核酸组)5组,每组6只。采用右肾切除加尾静脉注射阿霉素制成肾小球硬化动物模型。第8周各组大鼠给予不同的药物干预,在给药7d后,应用免疫组化技术检测肾组织核转录因子κB p65(NF-κB p65)、caspase-3的表达,原位末端转移酶标记法(TUNEL)检测肾小球细胞凋亡指数。结果E组NF-κB p65、caspase-3的表达及肾小球细胞凋亡指数与B组相比均明显降低。结论NF-κB反义核酸通过肾动脉给药可直接抑制肾组织NF-κB的表达,抑制肾小球系膜细胞凋亡,延缓肾小球硬化的进程。

Objective To investigate the intervention of antisense oligonucleotide targeting NF-κB to apoptosis in adriamycin-induced nephritic rats. Methods Male SD rats were divided into 5 groups（6 rats in each group） ：group A（ sham operation） ,group B（ glomerulosclerosis） ,group C（ sense oligonucleotide） ,group D（ non-sense oligonucleotide） ,and group E（antisense oligonucleotide） . Glomerulosclerosis model was made by unilateral nephrectomy as well as injection of adriamycin into the caudal vein. Various treatments were applied to corresponding groups in the 8th week. The expressions of nuclear factor-κB p65（NF-κB p65） and caspase-3 were measured by immunohistochemistry staining,and apoptosis in glomerulus was evaluated by TUNEL assay,at 7th day after intervention. Results The expressions of active-NF-κB p65 and caspase-3,and apoptosis index were significantly lower in group E than those in group B. Conclusions NF-κB antisense oligonucleotide could directly block the translation of NF-κB gene,suppress the apoptosis of glomerular membrane cells,and delay the progression of glomerulosclerosis.