抑制NF-κB活性对糖尿病大鼠肾脏TGF-β1 mRNA表达影响

The effect of inhibiting nuclear factor-κB activity on the mRNA expression of transforming growth factor-β1 in the diabetic kidneys

目的 研究抑制核因子 κB(NF κB)活性对糖尿病大鼠肾脏TGF β1mRNA表达影响。 方法 纯种♂Wistar大鼠分为 3组 :A组为正常对照组 (11只 ) ,B组为糖尿病大鼠未干预组 (11只 ) ,C组为糖尿病大鼠PDTC(NF κB活性抑制剂 )干预组 (9只 )。饲养 18wk后取出肾脏 :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 ) ,RT PCR检测TGF β1mRNA表达。酶免疫分析法检测 2 4h尿白蛋白排泄 (UAE)。结果 肾组织NF κB活性在B组大鼠肾组织 (1 85± 0 5 4× 10 6)显著高于A组 (0 0 7± 0 11×10 6,P <0 0 1) ,C组 (0 2 5± 0 2 5× 10 6)显著低于B组 (P <0 0 1)。B组与A组比较 ,UAE (2 18± 1 98mgvs 0 4 1± 0 4 7mg,P <0 0 1)、肾小球基底膜厚度 (5 31 6± 10 7 6nmvs 312 4±2 5 4nm ,P <0 0 1)及系膜基质密度 (5 6 4 1± 6 78vs 33 95±5 2 2 ,P <0 0 1)均显著增高 ;C组大鼠UAE(0 5 6± 0 72 )mg、肾小球基底膜厚度 (315 8± 2 1 4 )nm及系膜基质密度 (37 97±7 37)均显著低于B组 (均P <0 0 1)。肾组织TGF β1mR NA表达在B组大鼠 (0 5 3± 0 2 0 )显著高于A组 (0 2 6±0 13,P <0 0 1) ,C组 (0 2 9± 0 10 )显?

Aim To investigate the effect of inhibiting NF-κB activity on the mRNA expression of TGF-β1 in the diabetic kidneys. Methods The male Wistar rats were divided into: the group A was the normal rats, the group B was the diabetic rats without any treatment, and the group C was the diabetic rats treated with PDTC (an inhibitor of NF-κB activity). The diabetic model was made by the intraperitoneal injection of streptozotocin. After a period of 18 weeks, the kidneys were taken out from all the rats to examine the NF-κB activity by EMSA and the mRNA expression of TGF-β1 by RT-PCR, as well as to observe the glomerular basement membrane (GBM) thickening and mesangial matrix (MM) density(MM area/mesangial area) by electron microscope. Also the 24 h of urine albumin excretion (UAE) was measured. Results The renal NF-κB activity in group B (1.85± 0.54×10 6) was significantly higher than that in the group A (0.07±0.11×10 6, P<0.01), and in the group C (0.25±0.25×10 6) lower than in the group B(P<0.01). Compared with those in the 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 vs 33.95±5.22, P<0.01) were increased significantly in the group B,and all the UAE (0.56 ±0.72 mg),the GBM thickening (315.8±21.4 nm) and the MM density (37.97±7.37) in the group C lower significantly than those in the group B(all were P<0.01). The mRNA expression of TGF-β1 in group B(0.53±0.20)was increased significantly when compared with those in the group A(0.26±0.13,P<0.01)and in the group C(0.29±0.10,P<0.01).Conclusion Inhibiting NF-κB activity can delay the DN and decrease the mRNA expression of TGF-β1 in diabetic kidneys, suggesting that NF-κB may join in the pathogenesis of DN by way of TGF-β1.