P-gp170及HSP90在儿童原发性肾病综合征中的表达及其临床意义
发布时间：2018-08-03 18:26
【摘要】：目的检测P-糖蛋白170(P-gp170)及热休克蛋白90(HSP90)在原发性肾病综合征(PNS)患儿不同时间点外周血淋巴细胞及肾组织中的表达情况，探讨P-gp170与HSP90介导糖皮质激素(GC)耐药的可能机制及其临床意义。 方法选择在苏州大学附属儿童医院住院的PNS患儿20例，按照GC对患儿的疗效分成两组：激素耐药型肾病综合征(SRNS)和激素敏感型肾病综合征(SSNS),各10名，10名健康儿童作为正常对照组，分两个时间点采集外周血标本：（1）发病初未用GC时；（2）足量GC治疗4周后。进行如下实验：①流式细胞术(FCM)检测PNS患儿及正常对照组在不同时间点外周血淋巴细胞中P-gp170及HSP90的表达。②10例SRNS患儿均在激素治疗4周后行肾穿刺活检术，5例正常肾组织为对照，用免疫组织化学方法检测肾组织中P-gp170及HSP90的表达。 结果(1)SSNS组、SRNS组和正常对照组外周血淋巴细胞中均有P-gp170及HSP90的表达；(2)激素治疗前SSNS组、SRNS组外周血淋巴细胞中的P-gp170及HSP90高于正常对照组(P0.05)；激素治疗4周后SSNS组及SRNS组外周血淋巴细胞中的P-gp170明显高于治疗前(P0.05)，HSP90较前下降(P0.05)；(3)激素治疗前SRNS组外周血淋巴细胞中P-gp170明显高于SSNS组及正常对照组，，治疗后SRNS组外周血淋巴细胞中P-gp170较治疗前升高(P0.05)；激素治疗前SRNS组外周血淋巴细胞中HSP90明显高于SSNS组及正常对照组，治疗后SRNS组外周血淋巴细胞中HSP90较治疗前下降(P0.05),但仍高于正常对照组(P0.05)；(4) SRNS组与正常对照组患儿肾组织中P-gp170主要表达于肾小管及肾间质，SRNS组肾组织近曲小管P-gp170阳性率表达明显高于正常组(P0.05)，SRNS组内近曲小管P-gp170阳性率表达明显高于远曲小管(P0.05)。(5)正常对照组与SRNS组患儿肾组织中均有HSP90的表达，多在肾小球及肾小管的胞浆和胞核内表达，SRNS组患儿肾组织中HSP90表达明显高于正常对照组(P0.05)。(6)PNS患儿外周血淋巴细胞中P-gp170及HSP90的表达分别与24小时尿蛋白定量正相关(r分别为0.563,0.785，均P0.05), SRNS组患儿外周血淋巴细胞中P-gp170表达与SRNS组患儿肾脏近曲小管中P-gp170的灰度值及病理积分呈等级正相关(r分别为0.923,0.846，均P0.05), SRNS组患儿外周血淋巴细胞中HSP90表达与SRNS组患儿肾脏远曲小管中HSP90的灰度值及病理积分呈等级正相关(r分别为0.708,0.726，均P0.05), SRNS组肾脏病理积分与其24小时尿蛋白定量高度等级正相关(r=0.753, P0.05)。 结论(1)应用激素可能诱导PNS患儿外周血淋巴细胞P-gp170过度表达;(2)SRNS患儿肾组织中P-gp170的表达强度与病理积分明显正相关，外周血淋巴细胞及肾组织中P-gp170高表达可能参与了SRNS患儿激素耐药的发生和发展;(3)SRNS患儿外周血淋巴细胞及肾组织中HSP90高表达可能与激素耐药有关;(4)SRNS患儿外周血P-gp170及HSP90的表达一定程度上可反映肾脏病变的程度。
[Abstract]:Objective to detect the expression of P-glycoprotein 170 (P-gp170) and heat shock protein 90 (HSP90) in peripheral blood lymphocytes and renal tissues of children with primary nephrotic syndrome (PNS) at different time points. To explore the possible mechanism of glucocorticoid (GC) resistance mediated by P-gp170 and HSP90 and its clinical significance. Methods Twenty patients with PNS were enrolled in the affiliated Children's Hospital of Suzhou University. According to the curative effect of GC on children, they were divided into two groups: 10 healthy children with steroid-resistant nephrotic syndrome (SRNS) and 10 steroid-sensitive nephrotic syndrome (SSNS),) as normal control group. Peripheral blood samples were collected at two time points: (1) when GC was not used at the beginning of the disease; (2) after 4 weeks of full GC therapy. Detection of P-gp170 and HSP90 expression in Peripheral Blood lymphocytes of Children with PNS and normal controls by flow Cytometry as follows: 1: 1 flow Cytometry. The expression of P-gp170 and HSP90 in peripheral blood lymphocytes of children with SRNS at different time points. 5 cases of renal biopsy were performed after 4 weeks of hormone therapy. Normal renal tissue as control, The expression of P-gp170 and HSP90 in renal tissue was detected by immunohistochemistry. Results (1) the expression of P-gp170 and HSP90 in peripheral blood lymphocytes of SSNS group and normal control group was higher than that of normal control group (P0.05), (2) the expression of P-gp170 and HSP90 in peripheral blood lymphocytes of SSNS group was higher than that of normal control group before hormone therapy (P0.05). After 4 weeks of hormone therapy, the P-gp170 in peripheral blood lymphocytes in SSNS group and SRNS group was significantly higher than that before treatment (P0.05), and the P-gp170 in peripheral blood lymphocytes of SRNS group was significantly higher than that of SSNS group and normal control group before hormone therapy (P0.05). The level of P-gp170 in peripheral blood lymphocytes in SRNS group was higher than that before treatment (P0.05), and the HSP90 in peripheral blood lymphocytes in SRNS group was significantly higher than that in SSNS group and normal control group before hormone therapy. The level of HSP90 in peripheral blood lymphocytes of SRNS group was lower than that before treatment (P0.05), but still higher than that of normal control group (P0.05). (4) the positive rate of P-gp170 in renal tissue of SRNS group and normal control group was significantly higher than that of normal group (P0.05). The positive rate of P-gp170 in proximal convoluted tubules in renal tubules and interstitial tubules in SRNs group was significantly higher than that in normal control group (P0.05). The positive rate of P-gp170 expression in proximal convoluted tubules was significantly higher than that in distal tubules. The expression of HSP90 was found in renal tissues of normal control group and SRNS group (P0.05). (5). The expression of HSP90 in the renal tissues in the SRNs group was significantly higher than that in the normal control group (P0.05). (6). The expressions of P-gp170 and HSP90 in peripheral blood lymphocytes of the children with PNS were positively correlated with the 24 hour urine protein (r). The expression of P-gp170 in peripheral blood lymphocytes of children in), SRNS group was positively correlated with the gray value and pathological score of P-gp170 in proximal convoluted tubules of SRNS group (r = 0.923 卤0.846, respectively, P 0.05). The expression of P-gp170 in peripheral blood lymphocytes of children in), SRNS group was positively correlated with the HSP90 table in peripheral blood lymphocytes of children with SRNS group (r = 0.923 卤0.846, respectively). The grayscale value and pathological score of HSP90 in distal convoluted tubules were positively correlated with those in SRNS group (r = 0.708 卤0.726, P 0.05). The renal pathological scores in), SRNS group were positively correlated with the 24 hour urinary protein quantitative high grade (r 0.753, P 0.05). Conclusion (1) hormone may induce the overexpression of P-gp170 in peripheral blood lymphocytes of children with PNS, (2) the expression of P-gp170 in renal tissue of children with SRNS is positively correlated with the pathological score. The high expression of P-gp170 in peripheral blood lymphocytes and renal tissues may be involved in the occurrence and development of hormone resistance in children with SRNS; (3) the high expression of HSP90 in peripheral blood lymphocytes and renal tissues of children with SRNS may be related to hormone resistance; (4) the high expression of HSP90 in peripheral blood of SRNS children and children with SRNS; The expression of HSP90 can reflect the degree of renal lesion to some extent.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R726.9
本文编号：2162593
[Abstract]:Objective to detect the expression of P-glycoprotein 170 (P-gp170) and heat shock protein 90 (HSP90) in peripheral blood lymphocytes and renal tissues of children with primary nephrotic syndrome (PNS) at different time points. To explore the possible mechanism of glucocorticoid (GC) resistance mediated by P-gp170 and HSP90 and its clinical significance. Methods Twenty patients with PNS were enrolled in the affiliated Children's Hospital of Suzhou University. According to the curative effect of GC on children, they were divided into two groups: 10 healthy children with steroid-resistant nephrotic syndrome (SRNS) and 10 steroid-sensitive nephrotic syndrome (SSNS),) as normal control group. Peripheral blood samples were collected at two time points: (1) when GC was not used at the beginning of the disease; (2) after 4 weeks of full GC therapy. Detection of P-gp170 and HSP90 expression in Peripheral Blood lymphocytes of Children with PNS and normal controls by flow Cytometry as follows: 1: 1 flow Cytometry. The expression of P-gp170 and HSP90 in peripheral blood lymphocytes of children with SRNS at different time points. 5 cases of renal biopsy were performed after 4 weeks of hormone therapy. Normal renal tissue as control, The expression of P-gp170 and HSP90 in renal tissue was detected by immunohistochemistry. Results (1) the expression of P-gp170 and HSP90 in peripheral blood lymphocytes of SSNS group and normal control group was higher than that of normal control group (P0.05), (2) the expression of P-gp170 and HSP90 in peripheral blood lymphocytes of SSNS group was higher than that of normal control group before hormone therapy (P0.05). After 4 weeks of hormone therapy, the P-gp170 in peripheral blood lymphocytes in SSNS group and SRNS group was significantly higher than that before treatment (P0.05), and the P-gp170 in peripheral blood lymphocytes of SRNS group was significantly higher than that of SSNS group and normal control group before hormone therapy (P0.05). The level of P-gp170 in peripheral blood lymphocytes in SRNS group was higher than that before treatment (P0.05), and the HSP90 in peripheral blood lymphocytes in SRNS group was significantly higher than that in SSNS group and normal control group before hormone therapy. The level of HSP90 in peripheral blood lymphocytes of SRNS group was lower than that before treatment (P0.05), but still higher than that of normal control group (P0.05). (4) the positive rate of P-gp170 in renal tissue of SRNS group and normal control group was significantly higher than that of normal group (P0.05). The positive rate of P-gp170 in proximal convoluted tubules in renal tubules and interstitial tubules in SRNs group was significantly higher than that in normal control group (P0.05). The positive rate of P-gp170 expression in proximal convoluted tubules was significantly higher than that in distal tubules. The expression of HSP90 was found in renal tissues of normal control group and SRNS group (P0.05). (5). The expression of HSP90 in the renal tissues in the SRNs group was significantly higher than that in the normal control group (P0.05). (6). The expressions of P-gp170 and HSP90 in peripheral blood lymphocytes of the children with PNS were positively correlated with the 24 hour urine protein (r). The expression of P-gp170 in peripheral blood lymphocytes of children in), SRNS group was positively correlated with the gray value and pathological score of P-gp170 in proximal convoluted tubules of SRNS group (r = 0.923 卤0.846, respectively, P 0.05). The expression of P-gp170 in peripheral blood lymphocytes of children in), SRNS group was positively correlated with the HSP90 table in peripheral blood lymphocytes of children with SRNS group (r = 0.923 卤0.846, respectively). The grayscale value and pathological score of HSP90 in distal convoluted tubules were positively correlated with those in SRNS group (r = 0.708 卤0.726, P 0.05). The renal pathological scores in), SRNS group were positively correlated with the 24 hour urinary protein quantitative high grade (r 0.753, P 0.05). Conclusion (1) hormone may induce the overexpression of P-gp170 in peripheral blood lymphocytes of children with PNS, (2) the expression of P-gp170 in renal tissue of children with SRNS is positively correlated with the pathological score. The high expression of P-gp170 in peripheral blood lymphocytes and renal tissues may be involved in the occurrence and development of hormone resistance in children with SRNS; (3) the high expression of HSP90 in peripheral blood lymphocytes and renal tissues of children with SRNS may be related to hormone resistance; (4) the high expression of HSP90 in peripheral blood of SRNS children and children with SRNS; The expression of HSP90 can reflect the degree of renal lesion to some extent.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R726.9
【参考文献】
相关期刊论文 前9条
1 林莉;刘晓晴;王升启;;多药耐药基因的单核苷酸多态性研究进展[J];国外医学.药学分册;2006年01期
2 吴小川,易著文,何小解,党西强,赵维玲;小儿紫癜性肾炎肾脏病理定量分析[J];湖南医科大学学报;2000年04期
3 甘卫华,陈荣华,丁桂霞,龚晶,杨春,张文君;肾病综合征患儿肾组织中AP-1及TGF-β_1的表达与激素疗效关系的探讨[J];临床儿科杂志;2005年04期
4 朱光华;;激素耐药肾病的病理特点[J];临床儿科杂志;2007年12期
5 李志辉,易著文,何小解,吴小川;激素耐药型和激素依赖型肾病患儿肾脏病理计量分析[J];中华儿科杂志;2001年08期
6 叶建伟,丁洁,黄建萍,陈彦,姚勇,肖慧捷,杨霁云,沈颖,孟群;糖皮质激素受体基因多态性与肾病综合征患儿激素耐药相关性探讨[J];中华儿科杂志;2003年09期
7 何小解,易著文,党西强,张慧琼,何庆南,莫双红,白海涛,耿文茂,杨华彬;GRβ在原发性肾病综合征患儿糖皮质激素耐药中的作用[J];中华儿科杂志;2005年02期
8 钱小顺,朱元珏,许文兵,林耀广,李龙芸;热休克蛋白90和糖皮质激素受体比例失衡对哮喘患者T淋巴细胞凋亡的影响[J];中华医学杂志;2001年24期
9 欧阳涓;姜傥;谭敏;崔颖鹏;李晓艳;;HSP 90在原发性肾病综合征发生和治疗中的意义[J];中山大学学报(医学科学版);2006年06期
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