Objective To explore the role of P- glycoprotein( P- gp)170 in steroid resistant nephrotic syndrome(NS) and the mechanism involved.Methods Twenty- four children with NS without any glucocorticoid( GC ) treatment before GC administration were divided into 2 groups: steroid - sensitive NS (SSNS) group and steroid - responsive NS(SRNS) group according to the results of follow - up, with 10 healthy children serving as healthy control group.Each subject was treated with dexamethasone(Dex) and cultivated,and Western blot assay was adopted to test P - gpl70 expression in membrane of peripheral blood mononuclear cells( PBMC ) at different time points, namely at 0 h,12 h,24 h and 36 h,and at the same time,samples without Dex treatment serving as blank control.Results 1.No change was found of Pgp170 expressions in SSNS blank at different time points, thus no significant difference was found among them according to statistics( P ＞0.05 ) ;P- gp170 expressions in SSNS blank control at different time points were all higher compared with healthy blank control group, thus significant differences were found among them according to statistics( P ＜ 0.05 ) ;P- gpl70 expression in Dex -treated SSNS decreased by and by, with a significant difference among different time points statistically ( P ＜ 0.05 ); P - gp170 expression at different time points were all higher in Dex - treated SSNS compared with Dex - treated healthy controls, thus a significant difference was found among them according to statistics( P ＜0.05) ;P - gpl70 expression in Dex - treated SSNS were all higher than those of SSNS blank controls,thus a significant difference was found at each time point statistically( P ＜0.05 ).2.No change was found of P- gp170 expression in SRNS at different time points,thus no significant difference was found among them according to statistics( P ＞ 0.05 ) ;and there was difference of P- gp170 expression compared with healthy blank controls statistically( P ＜ 0.05 ); No change was found of P - gp170 expression in Dex - treated SRNS at different times, thus no significant difference was found among them according to statistics ( P ＞ 0.05 ); and statistically there was difference of Pgp170 expression level compared with SRNS ( P ＜ 0.05 ); P - gp170 expression at different time points were all lower compared with SRNS blank control, thus a significant difference was found among them according to statistics( Pa ＜ 0.05 ), and P -gp170 expression in Dex -treated SRNS of different time points were all lower, so significant differences were found among groups according to statistics( Pa ＜ 0.05 ), but no change of P- gpl70 expression in Dex -treated SRNS was found at different time points compared with SRNS blank control, thus no signiticant difference was found among them according to statistics ( P ＞ 0.05 ).Conclusions 1.Expression of P - gp170 is found both in healthy controls and children with NS with the later being higher than the former.2.Mechanism of some children with SRNS may attribute to up regulation of P - gp170 primarily.3.GC administration may lead to higher expression of P - gp170 in cell membrane,and a large amount of GC administration during a long period of time clinically may result in GC resistance by way of up - regulating the expression of P - gp170.%目的 探讨P-糖蛋白(P-gp)170在肾病综合征(NS)患儿糖皮质激素(GC)耐药中的作用及其介导耐药的可能机制.方法 选取24例初发未应用GC的NS患儿为病例组,根据随访结果将其分成GC敏感型NS组 (SSNS组)和GC耐药型NS组(SRNS组).10名健康体检儿童为健康对照组.将健康对照组和病例组的外周血单个核细胞(PBMC)均予地塞米松(Dex)处理,培养后分别在0 h、12 h、24 h、36 h不同时间点进行检测,同时以不加Dex作为空白对照,Western blot法检测SSNS组和SRNS组患儿PBMC膜P-gp170的表达量,并结合临床资料进行比较.结果 1.SSNS组空白对照各时间点PBMC膜表面P-gp170表达量比较差异无统计学意义(P>0.05),与健康对照组空白对照比较,该组各时间点P-gp170的表达量较高(P<0.05);Dex处理SSNS组患儿PBMC膜表面P-gp170表达随培养时间延长而渐降低(P<0.05),与Dex处理健康对照组比较,各时间点P-gp170的表达量较高(P<0.05);与SSNS组患儿空白对照比较,Dex处理SSNS组患儿PBMC膜表面各时间点P-gp170表达量较高(P<0.05).2.SRNS组患儿空白对照PBMC膜表面P-gp170表达随培养时间不同而无明显变化,不同时间点比较差异无统计学意义(P>0.05),与健康对照组空白对照比较,该组表达量升高(P<0.05),Dex处理SRNS组患儿PBMC膜表面P-gp170表达随培养时间的不同而无变化,各时间点P-gp170的表达量差异无统计学意义(P>0.05);与SRNS组患儿比较,SSNS组患儿空白对照各时间点P-gp170表达均较低(Pa<0.05),Dex处理SSNS组患儿各时间点P-gp170表达均较低(Pa<0.05);与SRNS组患儿空白对照比较,Dex处理SRNS组患儿各时间点PBMC膜表面P-gp170表达量比较差异无统计学意义(P>0.05).结论 1.健康儿童和NS患儿PBMC均有P-gp170表达,NS状态下可有P-gp170表达增高.2.SRNS患儿 PBMC膜P-gp170表达增高可能与GC耐药有关,P-gp170表达增高可能介导了部分NS患儿GC耐药.3.NS患儿PBMC膜P-gp170表达增高与GC应用有关,GC可能参与诱导P-gp170表达变化.
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