细胞型局灶节段性肾小球硬化症的病理变化及其细胞周期调控蛋白的表达

目的:探讨细胞型局灶节段性肾小球硬化症(focal segmental glomerulosclerosis,FSGS)的病理学特征及其细胞周期调控蛋白的表达.方法:收集细胞型FSGS病例17例,肾活检标本进行系统的光镜、免疫荧光及电镜观察,通过免疫组化及免疫电镜方法,检测细胞周期蛋白(cyclin D1,cyclin E,cyclin A及cyclin B1),细胞周期蛋白依赖激酶抑制剂(cyclin dependent kinase inhibitor-CKI,包括p2l,p27及p57)的表达.结果:细胞型FSGS以上皮细胞增生肥大伴有毛细血管襻的节段硬化或塌陷为突出特征;免疫荧光可见部分病例节段性IgM阳性或阴性;超微结构观察显示增生的细胞兼具足细胞及壁层上皮细胞的特征.细胞型FSGS的增生细胞,cyclin E、cyclin A、cyclin B1及p21表达阳性,而cyclin D1、p27及p57转为阴性.结论:细胞型FSGS的增生细胞可能为损伤的足细胞重现幼稚足细胞的表型特征,重新进入细胞周期进行增殖而形成细胞增生病变;细胞周期蛋白(cyclin E,cyclin A,cyclinB1)表达增加及CKI(p27,p57)表达降低与细胞增生病变的细胞周期调控有关.

The morphological characteristics and expression of cell cycle regulatory proteins in cellular variants of idiopathic focal segmental glomerulosclerosis

Objective: To investigate the morphological characteristics and expression of cell cycle regulatory proteins in cellular variants of idiopathic focal segmental glomerulosclerosis (FSGS). Methods: Seventeen cases of cellular variants of FSGS were studied by light microscopy, immunofluorescence (IF), and electron microscopy (EM). The immunohistochemistry and immunoelectron microscopy for the detection of cyclins (cyclin D1, cyclin E, cyclin A, cyclin B1) and cyclin dependent kinase inhibitors (CKIs, including p21, p27, p57) were performed in these cases. Results: The hypertrophy and hyperplasia of epithelial cells overlying sclerotic or collapsed glomerular tufts were the prominent characteristics of cellular variants of FSGS; IF showed segmental deposits of IgM; hyperplastic epithelial cells possessed the features of both podocyte and parietal epithelial cells ultrastructurally. Hyperplastic epithelial cells of cellular lesions showed positive staining for cyclin E, cyclin A, cyclin B1 and p21, and negative staining for cyclin D1, p27 and p57. Conclusion: The hyperplastic epithelial cells in cellular variants of FSGS may be derived from damaged podocytes, which mimic the immature podocytes, re engage the cell cycle to proliferate and form the cellular lesions. The up regulation of cyclins (cyclin E, cyclin A, cyclin B1) concurrent with the loss of CKIs (p27, p57) contributes to the cell cycle regulation of cellular lesions of FSGS.