El-Koraie Ahmed F, Baddour Nahid M, Adam Ahmed G, El-Kashef Essam H, El Nahas A Meguid
University of Alexandria, Alexandria, Egypt.
Nephrol Dial Transplant. 2002 May;17(5):803-12. doi: 10.1093/ndt/17.5.803.
Progression of renal diseases is related to the abnormal regulation of cellular and extracellular matrix turnover. Other factors in addition to schistosomal antigens may be relevant to the progression of schistosomal nephropathy (SN). The validity of markers of fibroblastic differentiation, alpha smooth muscle actin (alphaSMA), and vimentin, as well as the regenerative activity (PCNA/apoptosis index) in determination of progression of SN in comparison to other forms of non-schistosomal nephropathy (non-SN) is investigated.
Three groups were included; group I pure SN (n=16), group II a diverse group of non-schistosomal patients with comparable pathologic changes on renal biopsy (n=40) and a control group (n=5). Immunohistochemical staining of myofibroblasts (alphaSMA and vimentin) and proliferating cells (PCNA) and histomorphometric analysis was done. In situ end labelling (ISEL) of DNA was used to evaluate apoptosis.
No differences in the patterns of distribution of positivity of the different studied markers were observed between the different nephropathy groups. Both alphaSMA and vimentin were detected in glomerular mesangial, tubular epithelial, interstitial inflammatory fibroblast-like cells and occasionally endothelial cells. PCNA and apoptotic cells were detected in tubular epithelial and interstitial cells with paucity of positive cells in the glomerulus. Significant positive correlations were detected in group I between glomerular sclerosis and interstitial markers including interstitial alphaSMA (r=0.609, P=0.001), interstitial vimentin (r=0.812, P=0.00) and interstitial apoptosis (r=0.733, P=0.001). On the other hand, glomerulosclerosis in group II showed significant positive correlations with predominantly the glomerular markers; glomerular alphaSMA (r=0.475, P=0.002), glomerular apoptosis (r=0.684, P=0.00) and glomerular PCNA (r=0.691, P=0.00). Interstitial fibrosis correlated significantly with interstitial markers in group I including interstitial alphaSMA (r=0.837, P=0.00) interstitial vimentin (r=0.929, P=0.00), interstitial apoptosis (r=0.807, P=0.00) and interstitial PCNA (r=0.617, P=0.01), while in group II it correlated with both interstitial and glomerular markers. In addition, the tubulo-interstitial ratio was significantly higher in group I in comparison with group II (P=0.024), with no difference between groups II and III.
Although SN may start as glomerulopathy associated with increased mesangial cellularity, the interstitial rather than the glomerular markers of myofibroblastic differentiation and those of cell turnover are playing a crucial role in late stages of schistosomal, but not in non-schistosomal nephropathies.
肾脏疾病的进展与细胞和细胞外基质周转的异常调节有关。除血吸虫抗原外的其他因素可能与血吸虫性肾病（SN）的进展相关。本研究旨在探讨成纤维细胞分化标志物α平滑肌肌动蛋白（αSMA）和波形蛋白以及再生活性（PCNA/凋亡指数）在确定SN进展方面与其他形式的非血吸虫性肾病（非SN）相比的有效性。
纳入三组；第一组为单纯SN患者（n = 16），第二组为肾活检病理改变相似的不同类型非血吸虫病患者（n = 40），以及一个对照组（n = 5）。进行了肌成纤维细胞（αSMA和波形蛋白）和增殖细胞（PCNA）的免疫组织化学染色以及组织形态计量分析。采用DNA原位末端标记（ISEL）评估凋亡情况。
不同肾病组之间未观察到不同研究标志物阳性分布模式的差异。αSMA和波形蛋白均在肾小球系膜、肾小管上皮、间质炎性成纤维细胞样细胞以及偶尔的内皮细胞中检测到。PCNA和凋亡细胞在肾小管上皮和间质细胞中检测到，肾小球中阳性细胞较少。在第一组中，肾小球硬化与间质标志物之间存在显著正相关，包括间质αSMA（r = 0.609，P = 0.001）、间质波形蛋白（r = 0.812，P = 0.00）和间质凋亡（r = 0.733，P = 0.001）。另一方面，第二组中的肾小球硬化主要与肾小球标志物显著正相关；肾小球αSMA（r = 0.475，P = 0.002）、肾小球凋亡（r = 0.684，P = 0.00）和肾小球PCNA（r = 0.691，P = 0.00）。间质纤维化在第一组中与间质标志物显著相关，包括间质αSMA（r = 0.837，P = 0.00）、间质波形蛋白（r = 0.929，P = 0.00）、间质凋亡（r = 0.807，P = 0.00）和间质PCNA（r = 0.617，P = 0.01），而在第二组中它与间质和肾小球标志物均相关。此外，第一组的肾小管间质比显著高于第二组（P = 0.024），第二组和第三组之间无差异。
尽管SN可能始于与肾小球系膜细胞增多相关的肾小球病，但肌成纤维细胞分化的间质而非肾小球标志物以及细胞更新标志物在血吸虫性肾病的晚期阶段起关键作用，而在非血吸虫性肾病中并非如此。
