核因子κB反义寡核苷酸对肾小球硬化Caspase-3表达的影响

Effect of Antisense Oligodeoxynudeotides Targeting Nuclear Factor кB on Expression of Caspase-3 in Glomerulosclerosis

目的探讨核转录因子κB(NF-κB)反义寡核苷酸(ODN)对局灶性节段性肾小球硬化大鼠肾组织半胱氨酸天冬氨酸特异性蛋白酶(Caspase-3)、NF-κB表达影响。方法SD雄性大鼠分成3大组:假手术组(A组)、硬化组(B组)各6只,干预组(C组)9只;C组再分成3小组:正义ODN组(C1组)、无义ODN组(C2组)、反义ODN组(C3组)各3只。采用右肾切除加尾静脉注射多柔比星制成肾小球硬化模型。8周后各组分别予不同的药物干预,应用免疫组织化学检测肾组织Caspase-3、NF-κBp65表达。结果反义ODN干预d7,C3组大鼠尿蛋白、肾小球硬化指数、肾组织Caspase-3、NF-κBp65蛋白表达较B、C1、C2组明显减少,差异有统计学意义(Pa<0.05);C3组与A组比较,NF-κBp65蛋白表达无显著差异(P>0.05)。结论NF-κBODN能抑制肾小球NF-κB活性及Caspase-3表达,从而延缓肾小球硬化及细胞凋亡进程。

Objective To investigate the effect of antisense oligodeoxynudeotides（ODN）targeting nuclear factor κB（NF-κB）on the expressions of Caspase-3 and NF-κB in glomerulosclerosis.Methods Male SD rats were divided into 3 groups：sham operation（group A,n=6）,glomerulosclerosis（group B,n=6）,intervention（group C,n=9）.Group C was divided into 3 groups：sense ODN（group C1,n=3）,non-sense ODN（group C2,n=3）,antisense ODN（group C3,n=3）.Glomerulosclerosis models were made for SD rats by unilateral nephrectomy and being injected with adriamycin into caudal vein.After 8 weeks,various ODN applied to corresponding group for intervention.At the end of the 9th week,kidneys were taken out from all rats for the measurement of expressions of NF-κB p65 and Caspase-3 by immunohistochemistry staining.Results After intervention,on the d7,the rats urine protein,glomerular sclerosis index（GI）and expressions of Caspase-3,NF-κB p65 in group C3 were significantly lower than those in group B,C1,C2（Pa〈0.05）.The expression of NF-κB p65 had no significant effect between group C3 and group A（P〉0.05）.Conclusion Antisense ODN targeting NF-κB can inhibit the activities of NF-κB,Caspase-3 in rats kidneys and retard glomerulosclerosis and glomerular intrinsic cell apoptosis.