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狼疮性肾炎患儿肾组织中细胞凋亡及PDCD5和Caspase-3的表达

[Apoptosis and expressions of PDCD5 and Caspase-3 in renal tissues of children with lupus nephritis].

作者信息

Li Xin, Huang Jian-ping, Ding Jie

机构信息

Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.

出版信息

Zhonghua Er Ke Za Zhi. 2005 Jul;43(7):517-20.

Abstract

OBJECTIVE

To improve the understanding of the pathogenesis of lupus nephritis (LN) by studying the relationship between apoptosis and proliferation in children with LN.

METHODS

Thirty-one children (23 girls, 8 boys, aged 6-16 years) with biopsy-proven LN (21 type IV, 6 type V, 2 type II and 2 type III) and nine controls were included in the study. Apoptosis was detected by in situ nick-end labeling techniques (TUNEL) in renal biopsy samples. Proliferation was shown by PCNA detection. Immunohistochemistry was employed to detect the expressions of PCNA, PDCD5 and Caspase-3. The images of glomeruli (G) and renal tubuli (T) were selected randomly on each biopsy sample, respectively, and transferred into computer by SECOM video camera. The quantity of PDCD5 and Caspase-3 expressions were evaluated according to the average intensity of PDCD5 and Caspase-3.

RESULTS

  1. Compared to control group, the patients with LN had increased apoptotic cells (G: 0.14 +/- 0.09 vs. 0.86 +/- 0.26; T: 0.16 +/- 0.07 vs. 1.16 +/- 0.42; P < 0.01) and increased PCNA positive cells (G: 0.47 +/- 0.25 vs. 8.45 +/- 2.83; T: 1.32 +/- 0.15 vs. 13.73 +/- 3.54; P < 0.01) in glomeruli and renal tubuli. The high ratios of PCNA/apoptosis (P/A) were observed in glomeruli (3.37 +/- 1.93 vs. 10.01 +/- 2.96, P < 0.01) and tubuli (8.94 +/- 1.79 vs. 12.81 +/- 3.91, P < 0.05) in LN group. 2. There was no difference in expression of PDCD5 in glomeruli between LN children and controls (0.09 +/- 0.05 vs. 0.08 +/- 0.02, P > 0.05). The expression of PDCD5 in renal tubuli decreased significantly in LN children compared with controls (0.13 +/- 0.05 vs. 0.21 +/- 0.07, P < 0.01). 3. The expression of Caspase-3 in children with LN increased significantly in glomeruli and tubuli compared with that in controls (0.22 +/- 0.07 vs. 0.05 +/- 0.02; 0.08 +/- 0.03 vs. 0.05 +/- 0.01; P < 0.01). 4. The number of glomerular apoptotic cells showed a positive correlation with the expression of Caspase-3 (r = 0.718, P < 0.01), but no correlation with the expression of PDCD5 in all cases (r = 0.054, P > 0.05). The intensity of PDCD5 expression in glomeruli and renal tubuli showed no correlation with that of Caspase-3 expression in all cases (r = 0.061, P > 0.05, r = 0.049, P > 0.05). Stepwise multiple regression revealed that the number of apoptotic cells in renal tubuli correlated negatively with the intensity of PDCD5 expression, whereas correlated positively with intensity of Caspase-3 expression in all cases.

CONCLUSIONS

  1. Although the number of apoptotic cells in the kidney of LN was more than that in the kidney of control group, the apoptosis in the kidney of LN was relative insufficient compared with the proliferation. 2. Caspase-3 was involved in the apoptosis of glomeruli and renal tubuli of LN. 3. It was unclear if PDCD5 participated in the apoptosis of glomeruli of LN. While PDCD5 might participate the apoptosis of renal tubuli in LN.
摘要

目的

通过研究狼疮性肾炎(LN)患儿细胞凋亡与增殖之间的关系,提高对LN发病机制的认识。

方法

本研究纳入31例经活检证实为LN的患儿(23例女孩,8例男孩,年龄6 - 16岁)(21例IV型,6例V型,2例II型和2例III型)以及9例对照。采用原位缺口末端标记技术(TUNEL)检测肾活检样本中的细胞凋亡情况。通过检测增殖细胞核抗原(PCNA)显示细胞增殖情况。采用免疫组织化学法检测PCNA、程序性细胞死亡蛋白5(PDCD5)和半胱天冬酶 - 3(Caspase - 3)的表达。在每个活检样本上分别随机选取肾小球(G)和肾小管(T)的图像,通过SECOM摄像机传输至计算机。根据PDCD5和Caspase - 3的平均强度评估其表达量。

结果

  1. 与对照组相比,LN患儿肾小球和肾小管中凋亡细胞增多(G:0.14±0.09 vs. 0.86±0.26;T:0.16±0.07 vs. 1.16±0.42;P < 0.01),PCNA阳性细胞增多(G:0.47±0.25 vs. 8.45±2.83;T:1.32±0.15 vs. 13.73±3.54;P < 0.01)。LN组肾小球和肾小管中PCNA/凋亡(P/A)比值较高(3.37±1.93 vs. 10.01±2.96,P < 0.01)(8.94±1.79 vs. 12.81±3.91,P < 0.05)。2. LN患儿与对照组肾小球中PDCD5表达无差异(0.09±0.05 vs. 0.08±0.02,P > 0.05)。与对照组相比,LN患儿肾小管中PDCD5表达显著降低(0.13±0.05 vs. 0.21±0.07, P < 0.01)。3. 与对照组相比,LN患儿肾小球和肾小管中Caspase - 3表达显著增加(0.22±0.07 vs. 0.05±0.02;0.08±0.03 vs. 0.05±0.01;P < 立)。4. 在所有病例中,肾小球凋亡细胞数与Caspase - 3表达呈正相关(r = 0.718,P < 0.01),但与PDCD5表达无相关性(r = 0.054,P > 0.05)。在所有病例中,肾小球和肾小管中PDCD5表达强度与Caspase - 3表达强度均无相关性(r = 0.061,P > 0.05;r = 0.049,P > 0.05)。逐步多元回归显示,在所有病例中,肾小管凋亡细胞数与PDCD5表达强度呈负相关,而与Caspase - 3表达强度呈正相关。

结论

l. 虽然LN患儿肾脏中凋亡细胞数量多于对照组,但与增殖相比,LN患儿肾脏中的凋亡相对不足。2. Caspase - 3参与LN患儿肾小球和肾小管的凋亡。3. 尚不清楚PDCD5是否参与LN患儿肾小球的凋亡。而PDCD5可能参与LN患儿肾小管的凋亡。

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