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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。
Objective To investigate the role of P-glycoprotein (170) in glucocorticoid (GC) resistance in children with nephrotic syndrome (NS) and its possible mechanism of drug resistance. Methods Twenty-four non-GC-treated NS children were enrolled as case group. According to the follow-up results, they were divided into GC-sensitive NS group (SSNS group) and GC-resistant NS group (SRNS group). 10 healthy children were healthy control group. Peripheral blood mononuclear cells (PBMCs) of healthy control group and case group were treated with dexamethasone (Dex), and were detected at different time points of 0 h, 12 h, 24 h and 36 h respectively, Dex was added as a blank control. Western blot was used to detect the expression of P-gp170 in PBMC from SSNS and SRNS groups, and compared with clinical data. Compared with the control group, the expression of P-gp170 in the control group was not statistically significant (P> 0.05). Compared with the control group, the expression of P-gp170 in the group of SSNS at each time point was not significantly different (P <0.05). The expression of P-gp170 on the surface of PBMC in Dex treated SSNS children decreased gradually with the prolongation of culture time (P <0.05). Compared with Dex treated healthy children, the expression of P-gp170 (P <0.05). Compared with control group, the expression of P-gp170 in PBMC of SSNS group was higher than that of SSNS group (P <0.05). The expression of P-gp170 on the surface of PBMC in SRS group had no significant difference with the time of culture, and there was no significant difference at different time points (P> 0.05). Compared with the blank control group, the expression of P-gp170 (P <0.05). The expression of P-gp170 on the surface of PBMC in Dex-treated SRNS group did not change with the time of culturing. There was no significant difference in the expression of P-gp170 at each time point (P> 0.05) ; Compared with SRNS group, the expression of P-gp170 in SSNS group was lower (P <0.05), P-gp170 expression in each group was lower ). Compared with the control group, the expression of P-gp170 on the surface of PBMC in Dex-treated SRNS group was not significantly different at all time points (P> 0.05). P-gp170 expression was detected in PBMC from healthy children and NS children, and P-gp170 expression may be increased under NS status. The increased expression of P-gp170 in PBMC of SRNS children may be related to GC resistance, and the increased expression of P-gp170 may mediate GC resistance in some NS children. The increased expression of P-gp170 in PBMC of children with NS was related to the use of GC, GC may be involved in the induction of P-gp170 expression.