原发性肾病综合征患儿肾组织中p18的表达及意义(英文)

Expression of p18 in renal tissues of children with primary nephrotic syndrome

摘要:

目的：肾脏固有细胞的异常增生是肾小球硬化发展的病理基础，细胞增生又受细胞周期调控物质的调节。本研究通过探讨肾病综合征患儿肾组织细胞周期调节蛋白p18的表达水平及其与肾脏固有细胞增生之间的关系，为抑制肾脏固有细胞的异常增生，延缓肾脏病的慢性进展开辟新的途径。方法：以39例原发性肾病综合征患儿［8例微小病变(MCD)，15例系膜增生性肾小球肾炎(MsPGN)，7例膜增生性肾小球肾炎(MPGN)，9例局灶节段性肾小球肾炎(FSGS)］肾活检石蜡包埋肾组织及6例肾肿瘤肾切除病人的正常肾组织作为研究对象，用免疫组织化学方法检测了p18在肾组织的表达水平，分析其与肾病综合征的病理类型及肾组织中增殖细胞核抗原(PCNA)的表达的关系。结果：肾病综合征组肾小球内PCNA阳性细胞百分率(28.6%±3.4%)明显高于对照组(10.8%±3.4%)(P<0.05)，p18阳性细胞百分率(35.8%±4.0%)明显高于对照组(6.1%±1.9%)(P<0.05)；肾病综合征组肾小管-间质内的PCNA阳性细胞百分率(68.3%±11.6%)明显高于对照组(12.6%±2.6%)(P<0.05)。不同病理类型肾病综合征患儿的肾小球内PCNA阳性细胞百分率存在显著差异，分别为MCD 23.6%±4.6%，MsPGN 40.2%±5.1%，MPGN 27.5%±3.6%，FSGS 34.6%±5.1%(均P<0.05)；不同病理类型肾病综合征患儿的肾小球内p18阳性细胞百分率存在显著差异，分别为MCD 25.2%±4.3%，MsPGN35.7%±7.1%，MPGN 37.7%±4.0%，FSGS 40.1±6.4%(均P<0.05)。肾小球内p18的阳性细胞百分率和PCNA阳性细胞百分率成正相关(r=0.6632，P<0.05)。结论：肾病综合征患儿肾组织p18表达水平增加可能起促进异常增生的肾脏固有细胞消退的作用。［中国当代儿科杂志，2004, 6(5): 373-376］

Abstract:

OBJECTIVE: The abnormal proliferation of renal cells underlies the pathology of progressive glomerulosclerosis. Cell proliferation is regulated by cell cycle regulatory proteins. This study aims to investigate the expression of cell cycle regulatory protein p18 in renal tissues of the children with primary nephrotic syndrome (PNS), and to elucidate the relationship between p18 expression and cell proliferation. METHODS: Paraffin-embedded renal biopsy tissue sections from 39 patients with PNS [8 with minimal change disease (MCD), 15 with mesangialproliferative glomerulonephritis (MsPGN), 7 with membranoproliferative glomerulonephritis (MPGN), and 9 with focal and segmental glomerulosclerosis (FSGS)] were examined by immunohistochemical staining with anti-p18 monoclonal antibody and anti-proliferating cell nuclear antigen (PCNA) monoclonal antibody. Normal renal tissue sections from 6 nephrectomized patients with nephroma were used as controls. Possible correlation between the percentage of PCNA and p18 positive cells and their relationships with the pathological categories of PNS were evaluated. RESULTS: The percentage of PCNA positive cells ( 28.6%± 3.4%) in glomeruli of PNS patients was significantly higher than that of the controls ( 10.8%± 3.4%) (P< 0.05). The percentage of p18 positive cells ( 35.8%± 4.0%) in glomeruli of PNS patients was also significantly higher than that of the controls ( 6.0%± 1.9%) (P< 0.05). The percentage of PCNA positive cells ( 68.3%± 11.6%) in tubulointerstitium of PNS patients was significantly higher than that of the controls ( 12.6%± 2.6%) (P< 0.05) but there was no significant difference in the percentage of p18 positive cells in tubulointerstitium between the two groups. The percentages of PCNA positive cells in glomeruli of MCD, MsPGN, MPGN and FSGS were 23.6%± 4.6%, 40.2%± 5.1%, 27.5%± 3.6% and 34.6%± 5.1% respectively. There were significant differences among them (all P< 0.05). The percentage of p18 positive cells in glomeruli of MCD, MsPGN, MPGN and FSGS were 25.2%± 4.2%, 35.7%± 7.1%, 37.7%± 4.0% and 40.1%± 6.4% respectively. There were also significant differences among them (all P< 0.05). The percentage of p18 positive cells in glomeruli of PNS patients were positively correlated with the percentage of PCNA positive cells in glomeruli (r= 0.6632, P< 0.05). CONCLUSIONS: The overexpression of p18 in renal tissues of the children with PNS may promote the regression of abnormally proliferative cells in renal tissues.