抑制核因子-kB对糖尿病大鼠肾组织MT3-MMP mRNA表达的影响

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【目的】研究抑制NF鄄资B活性对糖尿病大鼠肾组织膜3型基质金属蛋白酶(MT3鄄MMP)mRNA表达的影响。【方法】纯种雄性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组为吡咯烷二硫基甲酸酯(PDTC,NF鄄资B活性抑制剂)干预组(9只)。以链脲佐菌素制备糖尿病模型。大鼠饲养18周后取出肾脏,以电泳迁移率变动分析技术检测NF鄄资B活性,RT鄄PCR检测MT3鄄MMPmRNA表达,以透射电镜检测肾小球基底膜厚度及系膜基质密度,并收集24h尿检测尿白蛋白排泄(UAE)。【结果】NF鄄资B活性在B组大鼠肾组织(1.85±0.54)×106明显高于A组(0.07±0.11)×106,P<0.01,C组(0.25±0.25)×106明显低于B组,P<0.01。肾组织MT3鄄MMPmRNA表达B组大鼠(1.37±0.96)明显高于A组(0.75±0.34),P<0.01,C组(0.75±0.36)明显低于B组(P<0.01)。与A组大鼠比较,肾小球基底膜厚度(531.6±107.6)nmvs(312.4±25.4)nm,P<0.01)及系膜基质密度(56.41±6.78)vs(33.95±5.22),P<0.01,均显著增高,C组肾小球基底膜厚度(315.8±21.4)nm及系膜基质密度(37.97±7.37)均显著低于B组,均P<0.01。UAE在B组大鼠(2.18±1.98)显著高于A组(0.41±0.47),P<0.05,以及C组(0.56±0.72),P<0.05。【结论】糖尿病大鼠肾组织NF鄄资B活性及MT3鄄MMPmRNA表达增加,抑制NF鄄资B活性可使肾组织MT3鄄MMPmRNA表达降低。 【Objective】 To investigate the effect of NF-κB inhibition on the expression of membrane-type-3 matrix metalloproteinase (MT3-MMP) mRNA in diabetic rats. 【Method】 Pure male Wistar rats were divided into three groups: A group as normal control group (11 rats), B group as diabetic rats without intervention group (11 rats), C group as pyrrolidine dithiocarbamate (PDTC, NF Juan B inhibitor) intervention group (9). Diabetes model was made by streptozotocin. After 18 weeks of rearing, the kidneys were removed, NF-κB activity was detected by electrophoretic mobility shift assay, MT3-MMP mRNA expression was detected by RT-PCR, and glomerular basement membrane thickness and mesangial matrix density were detected by transmission electron microscopy Urinary albumin excretion (UAE) 24 h urine test. [Results] The NF-B activity in renal tissue of B group was significantly higher than that of A group (0.07 ± 0.11) × 106, P <0.01, while that of C group (0.25 ± 0.25) × 106 was significantly lower In group B, P <0.01. The expression of MT3-MMP mRNA in renal tissue in group B (1.37 ± 0.96) was significantly higher than that in group A (0.75 ± 0.34), P <0.01, while in group C (0.75 ± 0.36) was significantly lower than that in group B (P <0.01). Compared with group A, glomerular basement membrane thickness (531.6 ± 107.6) nmvs (312.4 ± 25.4) nm, P <0.01) and mesangial matrix density (56.41 ± 6.78) vs (33.95 ± 5.22), P <0.01 , Both of which were significantly higher in group C. The thickness of glomerular basement membrane (315.8 ± 21.4) nm and mesangial matrix density (37.97 ± 7.37) in group C were significantly lower than those in group B (all P <0.01). UAE in group B (2.18 ± 1.98) was significantly higher than that in group A (0.41 ± 0.47), P <0.05, and in group C (0.56 ± 0.72), P <0.05. 【Conclusion】 NF-kappa B activity and MT3-MMP mRNA expression were increased in renal tissues of diabetic rats, and the decrease of MT3-MMP mRNA expression was found in renal tissues.
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