摘要
目的检测大鼠肾组织核转录因子-κB(NF-κB),血清IL-6、TNF-α的表达,探讨NF-κB与多柔比星肾病大鼠肾小球细胞炎性反应的关系及反义核酸的干预作用。方法SD雄性大鼠30只分为5组,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),E组(反义核酸组),每组6只。采用右肾切除加尾静脉注射多柔比星法作肾小球硬化动物模型。第8周各组大鼠予不同药物干预,给药3 d及7 d,分别检测各组大鼠24 h尿蛋白,HE染色观察其肾组织形态学变化,利用图像分析系统计算肾小球硬化指数(GI),应用免疫组织化学、酶联免疫吸附法检测其肾组织NF-κB p65,血清IL-6、TNF-α的表达。采用SPSS 10.0软件进行统计学分析。结果在不同的时间点,E组尿蛋白、GI、NF-κB p65、IL-6、TNF-α的表达与B组比较均显著降低,在7 d时间点,反义核酸的干预效应较3 d时间点强。结论NF-κB与肾小球硬化、细胞炎性反应存在密切关系。NF-κB反义核酸通过肾动脉给药可直接抑制肾组织NF-κB的翻译、表达,抑制肾小球系膜细胞的炎性反应,从而延缓肾小球硬化进程。
Objective To investigate the correlation between nuclear factor（NF）-κB and inflammation of cell in adriamycin-induced nephritic rats,and the intervention of antisense oligonucleotide targeting NF-κB to adriamycin-induced nephritic rats by measuring the expression of NF-κB p65 in renal cortex and the secretions of interleukin-6（IL-6）,tumor necrosis factor-α（TNF-α）in serum.Methods Thirty 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）,group E（antisense oligonucleotide）.Glomerulosclerosis models were made for SD rats by unilateral nephrectomy and being injected with adriamycin into caudal vein.In the 8^th week,various medicine applys to correspon-ding group for intervention.At the 4^th day and 8^th day after intervention,the excretion amounts of 24 hours urine protein were determined.Hematoxylin-Eosin（HE） staining was used to observe the renal pathological changes.Using image analysis system to calculate glomerulosclerosis index（GI）.The expression of NF-κB p65 in renal cortex was measured by immunohistochemistry staining,the secretions of IL-6,TNF-α in serum were performed by means of enzyme-linked immunosorbnent assay,respectively.Results At different time points,the expressions of active-NF-κB p65,IL-6,TNF-α in group E were significantly lower than those in group B.The intervention effects of antisense oligonucleotides at the 8^th day were stronger than that at the 4^th day.Conclusions NF-κB is significantly correlated with glomerulosclerosis and inflammations of glomerular intrinsic cells.Using NF-κB antisense oligonucleotide to be injected into renal artery can block directly the translation of NF-κB gene,delay inflammations of glomerular intrinsic cells and the progressions of glomerulosclerosis.
出处
《实用儿科临床杂志》
CAS
CSCD
北大核心
2008年第15期1190-1192,共3页
Journal of Applied Clinical Pediatrics
基金
广东省自然科学基金项目资助(04009576)
