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小儿肾小球疾病的肾小管上皮细胞表型特征及其纤维化关系探讨

Phenotypic changes of renal tubular epithelial cells and role of tubulointerstitial fibrosis in children with glomerular disease
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摘要 目的 探讨肾小管间质的损害、细胞的表型转化在小儿肾小球疾病进展中的作用 方法 对123例患 儿肾穿刺标本进行免疫组织化学染色,观察α平滑肌肌动蛋白(α-SMA)、波型蛋白(Vimentin,Vim)及Ⅳ型胶原(Col Ⅳ)的表达。对44例伴有小管间质损害的患儿进行增殖细胞核抗原(PCNA)的表达检测。结果 123例中:①肾小管间 质无损害者占23.6%,轻度损害者占46.3%,中度损害者占22.8%,重度损害者占7.3%。②肾小管间质有损害者,肾小 管上皮细胞可出现间质细胞标志物Vimentin及α-SMA的表达。③随着肾小管间质损害加重,α-SMA的表达增加,重 度损害者肾间质内出现大量α-SMA阳性细胞,并伴有Ⅳ型胶原(ColⅣ)的聚移增多;α-SMA的表达与肾小管间质损 害的程度、球性硬化及Scr呈正相关。④PCNA在轻度、中度损害肾小管间质病变时表达增加,在重度损害时表达减 弱。轻度、中度肾小管间质病变时,PCNA的表达与α-SMA的表达、肾小管间质损害及球性硬化呈正相关,与肌肝清 除率呈负相关 重度肾小管间质病变时,PCNA与肾小管间质损害程度、尿蛋白呈负相关 结论 随着肾小球疾病发 展,肾小管上皮细胞和间质成纤维细胞可发生向肾间质肌纤维母细胞的表型转化,参与肾间质纤维化的发展。肾小管 间质损害越重,患儿的病情也越重。 Objective The most common cause of chronic glomerulonephritis and chronic renal failure is glomeru-lonephritis in children. Kiichiro initiated the study for phenotypic changes of renal tubulomterstitial cells in human glumerulonephritis in 2000. Comprehensive reports combining the immunohistochemical study with the pathological and clinical data are rare.The aim of this study was to study the phenotypic changes of renal tubular epithelial cells in children with glumerulonephritis and the role of tubulomterstitial lesions(TIL) in children with glumerular diseases. Methods One hundred and twenty-three patients were hospitalized with glomerulonephritis from Jan. 1999 to Jan.2003. There were 65 males and 58 females,with a ratio of 1.12:1 ;their age ranged from 3 to 15 years old (average: 8.5±4.2 yr) ;the disease lasted from 1 to 36 months (average; 12.45±14.33) in general. Renal biopsy was indicated in all patients to determine the precise cause of the disease under the guidance of type B ultrasonographv. Normal renal tissues acquired from excisions of normal tissue from renal tumor surgery patients or from that of renal biopsy were chosen as control group. Routine light microscope examination was carried out to score the degree of the tubulointerstitial injury according to Katafuchi criterion. The tubu-lointerstitial injury included inflammatory cell infiltration,renal tubular atrophy and interstitial fibrosis,in which case the damages located in renal cortex. Immunohistochemical studies were performed in renal biopsy samples of 123 cases to detect the expression of phenotypic markers including α-smooth muscle actin(α-SMA) ,Vimentin(Vim) .cytokeratin (CK) and collagen Ⅳ (Col Ⅳ). Proliferating nuclear antigen (PCNA) expression was also analyzed in 44 cases with pathologic changes in renal tubular intestitium. Results Pathological abnormalities included 15 cases with minimal-change nephritic syndrome;1 case with intra -capillary proliferative glomerulonephritis; 54 cases with mesangial proliferative glomerulonephritis; 32 cases with IgA nephropathy;2 cases with membranous nephropathy;3 cases with focal segmental sclerosis;6 cases with proliferative sclerosis glomerulonephritis;6 cases with membranoproliferative glomerulonephritis and 4 cases with crescentic glomerulonephritis. Tubulointerstitial damages were found in 94 cases,which accounted for 76.4%. In 123 cases with glomerulonephritis, (1)No tubulointerstitial damage occurred in about 23.6% of patients,mild damage was present in 46.3% of patients,moderate damage was present in 22.8% and severe damage was present in 7.3%. (2)Both vimentin and α-SMA was positive in patients with tubulointerstitial damage. (3)There was an accumulation of α-SMA positive cells in interstitium, which were accompanied by increased deposition of collagen Ⅳ. α-SMA expression correlated closely with the severity of the tubulointerstitial damage, sclerosis, urine protein and blood pressure. (4)The α-SMA positive tubulointerstitial cells were also found to be PC-NA positive. The expression of PCNA was increased among patients with moderately severe renal tubulointerstitial damage,but decreased in children with severe tubulointerstitial damage. Conclusions With the progression of TIL .both renal tubular and interstitial cells may undergo phenotypic changes and that turned to become myofibroblast, which correlates with the interstitial fibrosis. TIL may be one of the key factors for the prognosis of children's glomerulonephritis.
出处 《临床儿科杂志》 CAS CSCD 北大核心 2004年第12期776-779,793,共5页 Journal of Clinical Pediatrics
关键词 儿童 肾小球疾病 肾小管间质 表型 细胞增殖 children glumerular disease tubulointerstitium phenotype cell proliferation
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参考文献10

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