Immunohistochemical expression of activated caspase-3 as a marker of apoptosis in glomeruli of human lupus nephritis
Immunohistochemical expression of activated caspase-3 as a marker of apoptosis in glomeruli of human lupus nephritis
复制标题
DOI：
10.1053/j.ajkd.2006.05.019
复制
发表时间：
2006-09-01
影响因子：
13.2
通讯作者：
Ferluga, Dusan
中科院分区：
文献类型：
--
作者：
Jeruc, Jera;Vizjak, Alenka;Ferluga, Dusan
背景细胞凋亡在狼疮性肾炎（LN）中的作用仍有争议。凋亡过程中的关键事件之一是caspase-3的激活。实验模型的研究表明，活化的caspase-3是凋亡率的可靠指标，与末端转移酶介导的DNA缺口末端标记（TUNEL）测定法相比具有有利的优势。我们的目的是研究细胞凋亡在各种形式的LN和它的关系，组织形态学的变化和选择的实验室研究结果，通过使用激活的caspase-3作为一种新的标志物的细胞凋亡。研究方法：我们研究了肾小球细胞凋亡的51例活检标本LN患者根据国际肾脏病学会/肾脏病理学会分类，采用TUNEL法和免疫组化对活化的caspase-3。此外，计算活动性和慢性指数，并使用抗Ki-67抗体来估计增殖活性。结果如下：活化的caspase-3阳性细胞存在于88.2%的病例的肾小球中，观察到肾小球簇和细胞和纤维细胞新月体。在肾小球簇中，它们主要见于具有活动性炎症病变的节段。Caspase-3免疫标记法与TUNEL法检测的凋亡指数具有良好的相关性（r = 0.72; P < 0.01）。凋亡指数与LN分级呈显著正相关（P < 0.001）。凋亡指数与活动指数、增殖指数和每日蛋白排泄量显著相关（P < 0.001），而与慢性指数、肌酐浓度和血清抗DNA抗体结合活性无关。结论：人LN中严重活动性肾小球病变的细胞凋亡率更高，表明细胞凋亡可能参与了人LN中炎症的增强。
Background. The role of apoptosis in lupus nephritis (LN) is still controversial. One of the key events in the process of apoptosis is activation of caspase-3. Studies of experimental models suggested that activated caspase-3 is a reliable indicator of apoptotic rate, with a favorable comparison against terminal transferase-mediated DNA nick-end labeling (TUNEL) assay. Our aim is to study apoptosis in various forms of LN and its relationship to histomorphological changes and selected laboratory findings by using activated caspase-3 as a novel marker of apoptosis. Methods: We investigated glomerular cell apoptosis in 51 biopsy specimens from patients with LN classified according to the International Society of Nephrology/Renal Pathology Society classification by using the TUNEL method and immunohistochemistry against activated caspase-3. In addition, activity and chronicity indices were calculated and anti-Ki-67 antibody was used to estimate proliferative activity. Results: Activated caspase-3-positive cells were present in glomeruli of 88.2% of cases, observed in the glomerular tuft and cellular and fibrocellular crescents. In the glomerular tuft, they were found mainly in segments with active inflammatory lesions. There was good correlation between apoptotic index assessed by using activated caspase-3 immunolabelling and the TUNEL method (r = 0.72; P < 0.01). We observed a significant positive correlation between apoptotic index and LN class (P < 0.001). Apoptotic index correlated significantly with activity index, proliferation index, and daily protein excretion (P < 0.001), but not chronicity index, creatinine concentration, or anti-DNA anti body-binding activity in serum. Conclusion: Apoptotic rate is greater in severe active glomerular lesions in human LN, suggesting that apoptosis may be involved in augmenting inflammation in human LN.