肾小管间质病变与慢性肾脏疾病进展关系的研究

A study of the relationship between renal tubulointerstitial damage and progression of chronic renal disease

目的 探讨慢性肾脏疾病进展与肾间质病变的关系及细胞增殖、凋亡失衡在肾脏疾病进展中的作用。方法 对 40例原发性肾脏疾病的肾功能与肾小管间质病变程度进行相关性分析 ,应用原位末端标记法(TUNEL)及免疫组织化学技术检测细胞凋亡 ,观察PCNA ,Fas FasL ,Bcl 2 ,Bax在肾小管间质的表达。结果 肾小管间质病变程度与血肌酐之间存在明显的正相关 (r =0 .5 9,P =0 .0 0 1) ;PCNA在中度肾小管间质病变时表达增加 ,重度病变时表达减少 (r =- 0 .6 8,P =0 .0 2 1) ;Bax的表达随肾小管间质病变的加重而增加 (r =0 .46 ,P =0 .0 0 43) ;肾小管间质内未见明显的细胞凋亡 ,Fas FasL ,Bcl 2的表达在不同程度的肾小管间质损害之间无统计学差异。结论 本研究提示肾小管间质病变的严重程度与慢性肾病进展相关 ,肾小管间质损害程度可作为判断慢性肾病预后的指标。肾小管间质的损害、纤维化与细胞增殖、凋亡失衡有关 ,肾小管间质中度损害时以细胞增殖为主 。

Objective To study the relationship between progression of chronic renal disease and renal tubulointerstitial damage, the effect of the imbalance of cell proliferation and apoptosis on progressive renal disease. Methods Correlative analysis between renal function and the degree of renal tubulointerstitial damage was made on 40 cases of primary renal diseases. Renal tubulointerstitial cell apoptosis and PCNA, Fas FasL, Bcl 2, Bax proteins expression were detected using immunohistochemical staining and terminal uridine deoxynucleotide nick end labeling (TUNUL) technique.Results There was a positive correlation between serum creatinine and the degree of tubulointerstitial damage ( r =0.59, P =0.0001). The expression of PCNA was increased among patients with intermediate renal tubulointerstitial damage and decreased in patients with severe tubulointerstitial damage ( r = 0.68, P =0.021). The expression of Bax gene increased with the degree of tubulointerstitial damage ( r =0.46, P =0.0043). The expression of apoptosis was inconspicuous in tubulointerstitial area, and the expression of Fas FasL, Bcl 2 among the patients with different degree of tubulointerstitial damage has not reached statistical significance.Conclusion This study shows that the degree of renal tubulointerstitial damage is correlated with the progression of chronic renal diseases and it can be used as a prognostic marker for prognosis in chronic renal diseases. Renal tubulointerstitial damage and fibrosis are associated with the imbalance of the cell proliferation and apoptosis. The expression of cell proliferation was increased in patients with moderately severe tubulointerstitial damage but decreased in patients with severe tubulointerstitial damage. The expression of the gene which stimulates apoptosis(Bax) was increased with the degree of tubulointerstitial damage.(Shanghai Med J, 2001,24∶75 77)