摘要
目的 研究抑制核因子 κB(NF κB)活性对糖尿病肾病 (DN)及糖尿病大鼠肾组织纤维连接蛋白 (FN)mRNA表达的作用。方法 将纯种雄性Wistar大鼠分为 :A组为正常对照组 (1 1只 ) ,B组为糖尿病无干预组 (1 1只 ) ,C组为吡咯烷二硫基甲酸酯 (PDTC ,NF κB抑制剂 )干预组 (9只 )。饲养 1 8周后 ,以电泳迁移率变动分析技术检测肾组织NF κB活性 ,透射电镜检测肾小球基底膜厚度及系膜基质密度 (系膜基质面积 /系膜面积 ) ,逆转录PCR检测FNmRNA表达 ,收集 2 4h尿测定尿白蛋白排泄率 (UAE)。结果 NF κB活性在B组大鼠肾组织 [(1 85± 0 54)× 1 0 6 ]显著高于A组 [(0 0 7± 0 1 1 )×1 0 6 ,P <0 0 1 ] ,C组 [(0 2 5± 0 2 5)× 1 0 6 ]显著低于B组 (P <0 0 1 )。B组与A组比较 ,UAE[(2 1 8±1 98)mgvs (0 41± 0 47)mg ,P <0 0 1 ]、肾小球基底膜厚度 [(531 6± 1 0 7 6)nmvs (31 2 4± 2 5 4)nm ,P<0 0 1 ]及系膜基质密度 [(56 41± 6 78)vs (33 95± 5 2 2 ) ,P <0 0 1 ]均有显著差异 ;UAE(0 56± 0 72 )mg、肾小球基底膜厚度 (31 5 8± 2 1 4)nm及系膜基质密度 (37 97± 7 37)在C组均显著低于B组 (P值均 <0 0 1 )。FNmRNA表达在B组大鼠肾组织 (0 73± 0 2 6)显著高于A组 (0 31±
Objective To investigate the effect of inhibiting nuclear factor kappa B(NF κB) on diabetic nephropathy(DN) and mRNA expression of fibronectin(FN) in diabetic kidneys. Methods Male Wistar rats were divided into 3 groups: group A ( n = 11) the normal rats, group B ( n =11) the diabetic rats without any therapy, and group C ( n =9) the diabetic rats treated with pyrrolidine dithiocarbamate (an inhibitor of NF κB). At the end of 18th week, the kidneys were taken out from all the rats to measure the NF κB activity by electrophoretic mobility shift assays (EMSA) and the mRNA expression of FN by reverse transcript (RT) PCR, as well as to observe the glomerular basement membrane (GBM) thickening and mesangial matrix (MM) density(MM area/mesangial area) by electronic microscope. 24 hour urine was also collected to measure the levels of albumin (urine albumin excretion, UAE). Results NF κB activity of renal tissue in group B [(1.85± 0.54)×10 6] was significantly higher than that in group A [(0.07±0.11)×10 6, P <0.01] and the activity in group C [(0 25±0.25)×10 6] lower than that in group B( P <0.01). Compared with those in group A,the UAE [(2 18±1 98)mg vs (0.41±0.47)mg, P <0.01],the GBM thickening [(531.6±107.6)nm vs (312.4±25.4)nm, P <0.01] and the MM density (56.41±6.78) in group B were significantly higher. The UAE [(0.56 ±0.72)mg], the GBM thickening [(315.8±21.4)nm] and the MM density (37.97±7.37) in group C were significantly lower than those in group B(all were P <0.01). The renal mRNA expression of FN in group B (0.73±0.26) was significantly higher than that in group A(0.31±0.15, P <0.01),while the expression in group C (0.26±0 06) was lower than that in group B ( P <0.01). Conclusion NF κB is activated in the diabetic kidneys. The inhibition of NF κB can slow down the development of DN and decrease the mRNA expression of FN in diabetic kidneys. Our data suggest that NF κB may play an important role in the development of DN.
出处
《中华内科杂志》
CAS
CSCD
北大核心
2002年第9期605-609,共5页
Chinese Journal of Internal Medicine
