【摘要】 目的探讨慢性马兜铃酸肾病。肾小管上皮细胞转分化与肾间质纤维化的关系。方法以慢性马兜铃酸肾病患者的肾组织为标本,作常规Masson染色化病理检查;用天狼星红组织化学(组化)染色检查胶原Ⅰ、Ⅲ表达;用免疫组化染色检查角蛋白(CK)、α-平滑肌肌动蛋白(α-SMA)、波形蛋白(Vim)及转化生长因子-β1(TGF-β1)表达。对结果进行定量或半定量分析。结果 肾间质Masson染色纤维化面积及胶原Ⅰ、Ⅲ面积,与肾小管间质α-SMA及Vim阳性表达面积呈显著正相关(P<0.05),与肾小管CK阳性表达面积呈显著负相关(P<0.05);病变过程中健存肾小管TGF-β1表达明显增强。结论慢性马兜铃酸肾病患者的肾小管上皮细胞可转分化为肌成纤维细胞,参与肾间质纤维化,而这细胞转分化很可能与其自身高表达TGF-β1相关。更多还原

【Abstract】 Objective To investigate the relationship between tubular cells transdifferentiation and renal interstitial fibrosis in patients with chronic aristolochic acid nephropathy (CAAN). Methods Specimens from renal biopsies of 10 CAAN patients with serum creatinine level of (309. 41 ± 164. 44) μmol/L were performed to examine the extent of renal interstitial fibrosis by Masson staining, the expression of collagen types Ⅰ and Ⅲ by sirius red staining, and the expression of cytokeratin(CK), α-smooth muscle actin (a-SMA), vimentin (Vim) and transforming growth factor-β 1 (TGF-β1) by immunohistochemical staining. Quantitative analysis by computer image analytic system or semi-quantitative analysis were used to evaluate the data. Results There was positively significant correlation between interstitial collagen types Ⅰ and Ⅲ and serum creatinine level ( r =0. 890, P < 0. 001) . Positive Vim expression was only found on a few interstitial cells of normal renal tissue. Both α-SMA and Vim were extensively expressed on tubulointerstitial cells in the renal tissue of CAAN and their expression was positively correlated with interstitial collagen types Ⅰ and Ⅲ (r =0. 836, P < 0. 01 and r = 0. 692, P < 0. 05, respectively) . CK was positive in normal tubular epithelial cells and the expression was negatively correlated with interstitial collagen types Ⅰ and Ⅲ ( r = - 0. 884, P <0. 001) . The expression of TGF-β1 on non-atrophic proximal tubular epithelial cells became much stronger in CAAN compared to that in normal renal tissue. Conclusions In the patients with CAAN a part of tubular epithelial cells are transdifferentiated into myofibroblasts, which may participate in interstitial fibrosis. The transdifferentiation of tubular epithelial cells may be related to the over-expression of TGFβ1 in these cells.更多还原