衰老大鼠肾小管间质细胞表型转化及意义

Phenotypic changes of renal tubulointerstitial cells during the process of aging in rats and its significance

目的通过检测肾小管间质细胞表型转化的标志物,明确其在肾脏衰老过程中的意义。方法选用3月、12月与24月Wistar大鼠,采用免疫组化方法检测肾小管间质中细胞表型标志α平滑肌肌动蛋白(α-SMA),细胞增殖标志。增殖性细胞核抗原(PCNA)与细胞外基质[Ⅰ型胶原、Ⅲ型胶原、纤连蛋白(FN)]在不同月龄大鼠肾小管间质中的表达。采用真彩医学图像分析系统进行定量分析。结果肾小管间质随增龄出现明显的病理变化。24月龄大鼠肾间质中α-SMA表达明显增多,而在3月龄除血管平滑肌外未见间质中阳性表达。PCNA在12月龄表达最为明显,与3月龄与24月龄存在显著性差异(P<0.05)。肾小管间质中细胞外基质Ⅰ型胶原、Ⅲ型胶原及FN随着增龄表达明显增加,24月龄与3月龄及12月龄相比存在显著性差异(均P<0.05)。Ⅰ型胶原、FN与间质纤维化程度呈正相关(r=0.63与r=0.78,均P<0.01)。结论衰老大鼠肾小管间质细胞表型发生明显变化,这种细胞表型的转化可能参与了肾脏的衰老结构的改变与功能的减退。

Objective By detecting phenotypic transforming marker of renal tubulointerstitial cells to determine its significance during the process of aging in rats. Methods Immunohistochemical studies were performed to detect the phenotypic markers including α-smooth muscle actin （ct-SMA）, proliferative cell nuclear antigen （PCNA）, collagen Ⅰ , collagen Ⅲ and fibronectin in renal tubulointerstitium of rats divided into 3-month-old group, 12-month-old group and 24-month-old group. A quantitative analysis of the expressions among experimental groups was performed by image analysis system. Results Significant pathological changes were found in renal tubulointerstitium with aging. The expression of α-SMA significantly increased with aging in tubulointerstitium in 24-month-old group, but without positive expression except vascular smooth muscle in 3-month-old group. 12-month-old group has the highest expression of PCNA, comparing to 3-month-old group and 24-month-old group（P 〈0.05）. Expressions of collagen Ⅰ , collagen Ⅲ and fibronectin significantly increased with aging（ P 〈 0. 05 ）, there were significant differences among three groups（P 〈0.05）. Collagen Ⅰ and fibronectin were correlated positively with interstitial fibrosis （ r = 0. 63 and 0. 78 respectively, P 〈 0. 01 ）. Conclusions Renal tubulointerstitial cells undergo phenotypic change during the process of aging, which may play an important role in the structural change and functional decline of kidney aging.