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狼疮性肾炎(IV 型)和膜增生性肾小球肾炎中的细胞凋亡与增殖细胞核抗原

Apoptosis and proliferating cell nuclear antigen in lupus nephritis (class IV) and membranoproliferative glomerulonephritis.

作者信息

Kirim Sinan, Tamer Tetiker, Saime Paydaş, Gönlüşen Gülfiliz

机构信息

Department of Internal Medicine, Faculty of Medicine, Cukurova University, Adana, Turkey.

出版信息

Ren Fail. 2005;27(1):107-13. doi: 10.1081/jdi-42724.

Abstract

BACKGROUND

The role of apoptosis in the pathogenesis of renal diseases has not been clearly established. Proliferating cell nuclear antigen (PCNA) is also a proliferation marker. In this study, we investigated the relationship between clinical course and PCNA apoptosis on baseline renal biopsy in patients with Lupus nephritis (LN) and membranoproliferative glomerulonephritis (MPGN).

METHODS

Thirty-nine patients with proliferative glomerulonephritis [lupus nephritis (LN)[21] and MPGN[18]] were included in this study. PCNA and apoptosis on renal biopsies were detected by immunohistochemical and terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) methods, respectively. We calculated the ratios of intraglomerular apoptotic cells and PCNA positive cells per glomeruli, and total numbers of apoptotic tubular cells and PCNA positive tubular cells among the 100 tubular cells, and PCNA positive cell and apoptotic cell on two different tubulointerstitial areas (40 x 10).

RESULTS

In LN: Apoptotic indexes of glomerulus and tubulus were 1.08+/-0.49 and 3.71+/-1.38, respectively. PCNA positivities were found at 16.76+/-11.34%, 46.57+/-22.54%, and 40.28+/-23.14% on glomerulus, tubulus, and interstitium, respectively. The activity index was 11.23+/-3.41, and the chronicity index was 3.81+/-1.99. In MPGN: Apoptotic indexes were found at 0.83+/-0.25 and 3.55+/-1.75 on glomerulus and tubulus, respectively. PCNA positivities were found at 21.33+/-18.42%, 35.5+/-25.99%, and 34.66+/-26.84% on glomerulus, tubulus, and interstitium, respectively. In controls, apoptosis was not found. In LN: PCNA positivity on tubulus and interstitium were correlated with the activity index (r = 0.768, p < 0.001, r = 0.721, and p < 0.001, respectively). Glomerular PCNA and apoptosis on interstitium and glomerulus were not correlated with the activity index. The activity index also was not correlated with creatinine clearance and daily proteinuria (p = 0.35 for both). At the end of the first year, patients with recovered or stabilized renal function had higher interstitial and tubular PCNA than others in G1 and G2.

CONCLUSION

It can be said that expression of PCNA on renal biopsy was correlated with activity indexes in LN. PCNA may be a prognostic indicator in MPGN and LN. However, apoptosis does not have a predictive value for MPGN and LN.

摘要

背景

细胞凋亡在肾脏疾病发病机制中的作用尚未明确。增殖细胞核抗原(PCNA)也是一种增殖标志物。在本研究中,我们调查了狼疮性肾炎(LN)和膜增生性肾小球肾炎(MPGN)患者基线肾活检时临床病程与PCNA凋亡之间的关系。

方法

本研究纳入了39例增殖性肾小球肾炎患者[狼疮性肾炎(LN)21例和MPGN 18例]。分别采用免疫组化和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)法检测肾活检组织中的PCNA和凋亡情况。我们计算了每个肾小球内凋亡细胞与PCNA阳性细胞的比例,以及100个肾小管细胞中凋亡肾小管细胞和PCNA阳性肾小管细胞的总数,以及两个不同肾小管间质区域(40×10)的PCNA阳性细胞和凋亡细胞数。

结果

在LN中:肾小球和肾小管的凋亡指数分别为1.08±0.49和3.71±1.38。肾小球、肾小管和间质的PCNA阳性率分别为16.76±11.34%、46.57±22.54%和40.28±23.14%。活动指数为11.23±3.41,慢性指数为3.81±1.99。在MPGN中:肾小球和肾小管的凋亡指数分别为0.83±0.25和3.55±1.75。肾小球、肾小管和间质的PCNA阳性率分别为21.33±18.42%、35.5±25.99%和34.66±26.84%。在对照组中,未发现凋亡。在LN中:肾小管和间质的PCNA阳性率与活动指数相关(r = 0.768,p < 0.001;r = 0.721,p < 0.001)。肾小球PCNA以及间质和肾小球的凋亡与活动指数无关。活动指数也与肌酐清除率和每日蛋白尿无关(两者p = 0.35)。在第一年结束时,肾功能恢复或稳定的患者在G1和G2期的间质和肾小管PCNA高于其他患者。

结论

可以说,肾活检中PCNA的表达与LN的活动指数相关。PCNA可能是MPGN和LN的预后指标。然而,细胞凋亡对MPGN和LN没有预测价值。

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