摘要
目的观察吡咯烷二硫氨基甲酸(pyrrolidine dithiocarbamat,PDTC)对大鼠急性肾损伤(acute kid-ney injury,AKI)的保护作用及其可能机制。方法实验分为假手术组、AKI组和PDTC组,各组再按取材时间分为3、6、12、24、48 h组。检测不同时间点血清肌酐(serum creatinine,SCr)和尿素氮(blood urea nitrogen,BUN)水平;苏木素和伊红染色观察肾脏的组织学改变;Western blotting法检测进入肾细胞核内的核因子-кB(nuclear factor-кB,NF-кB)p65蛋白的表达;酶联免疫吸附试验检测法检测肾组织肿瘤坏死因子-α(tumor nec-rosis factor-α,TNF-α)和细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)的水平;检测肾组织丙二醛(malondialdehyde,MDA)的水平和总抗氧化能力(total antioxidative capacity,T-AOC)。结果 PDTC组大鼠肾功能及肾组织的病理变化均较AKI组显著减轻。PDTC组各时间点肾组织T-AOC高于AKI组(P<0.01);而MDA、TNF-α和ICAM-1水平均明显低于AKI组(P<0.01),高于假手术组(P<0.01)。PDTC组肾细胞核内NF-кB p65蛋白表达较AKI组明显减少(P<0.01),且其表达变化与TNF-α、ICAM-1、MDA和T-AOC水平的变化密切相关(r分别为0.487、0.614、0.436、-0.283,P<0.01)。结论 PDTC可能通过抑制NF-кB活化,从而减少TNF-α和ICAM-1的产生,并减轻氧化应激损伤,对急性肾损伤起保护作用。
ObjectiveTo investigate the protective mechanism of pyrrolidine dithiocarbamat on the rat kidney from acute kidney injury. MethodsNinety male rats were randomly divided into sham operation group, acute kidney injury （AKI） group and pyrrolidine dithiocarbamat （PDTC） group,five subgroups at time points of 3 h,6 h,12 h,24 h and 48h after releasing clamps were set up in each group. The serum levels of serum creatinine （SCr） and blood urea nitrogen （BUN） were detected at the indicated time points. Pathological changes of kidney were observed by hematoxy and eosin （HE） stain. Expression of nuclear factor κB （NF кB） p65 protein entering the cell nucleus in kidney was detected by Western blot. Renal tumor necrosis factor α （TNF α） and intercellular adhesion molecule 1 （ICAM 1） levels were detected by ELISA. The renal levels of malondialdehyde （MDA） and total antioxidative capacity （T AOC） were detected.ResultsThere was dramatical mitigation in the change of renal function and pathomorphology in PDTC group compared with AKI group.The renal levels of T AOC in PDTC group were higher than those in AKI group at each time point （P〈0.01）,while the levels of MDA,TNF α and ICAM 1 in PDTC group were significantly lower than those in AKI group （P〈0.01） and higher than those in sham group （P〈0.01）.The expression of NF кB p65 protein in cell nucleus of kidney in PDTC group was distinctly lower compared with AKI group （P〈0.01）,and a significant correlation was found between the expression of NF кB p65 and the levels of TNF α,ICAM 1,MDA and T AOC （r=0487,r=0614,r=0436,r=-0283,P〈0.01）. ConclusionPDTC has a protective effect on AKI probably by down regulating the levels of TNF α and ICAM 1 and attenuating oxidative stress injury through inhibiting NF кB.
出处
《转化医学杂志》
2013年第3期133-136,共4页
Translational Medicine Journal
基金
四川省卫生厅自然科学基金(120373)
泸州市科技计划项目(2012-S-36)
关键词
吡咯烷类
核因子
кB
急性肾损伤
细胞因子
丙二醛
总抗氧化能力
Lower urinary tract infection Therapeutic regimen Pharmacoeconomics Serum pharmacology Translational medicine
