亲环素D对氧化应激诱发的肾小管上皮细胞坏死的影响

发布时间：2019-01-20 14:50

【摘要】：目的探讨亲环素D(CypD)在氧化应激时对肾小管上皮细胞坏死的影响。方法 Wistar雄性大鼠随机分对照组(n=6)、假手术组(n=6)及缺血再灌注组(n=6),观察各组血肌酐及肾小管坏死情况。体外培养人近端肾小管上皮细胞HK-2细胞系,以不同浓度(0.75、1.5、3 mmol/L)过氧化氢作用12 h及以1.5 mmol/L过氧化氢作用HK-2细胞不同时间(6、12、24 h),观察不同处理条件下细胞的坏死情况;使用环孢素A(CsA)或CypD-siRNA预处理、1.5 mmol/L过氧化氢作用HK-2细胞12 h后,观察细胞坏死情况。结果缺血再灌注组大鼠的血肌酐较对照组及假手术组明显升高(P=0.017,P=0.018);肾组织行HE染色,可见缺血再灌注组近端肾小管明显扩张、刷状缘消失,并存在大量管型、细胞空泡变性以及上皮细胞坏死脱落,对照组和假手术组未见肾脏组织损伤。H_2O_2刺激HK-2细胞系,细胞坏死呈时间及浓度依赖性,随着作用时间增加及H_2O_2浓度的增加,HK-2细胞坏死率显著增加;CypD-siRNA及CypD抑制剂CsA均可明显减轻H_2O_2所诱导的细胞坏死(P=0.026,P=0.008)。结论 CypD介导了氧化应激诱发的肾小管上皮细胞坏死,通过抑制CypD可以改善氧化应激下肾小管上皮细胞的存活率,从而在一定程度上减少缺血再灌注诱发的急性肾损伤。
[Abstract]:Objective to investigate the effect of cyclophile D (CypD) on renal tubular epithelial cell necrosis during oxidative stress. Methods male Wistar rats were randomly divided into three groups: control group (nong6), sham-operated group (nong6) and ischemia reperfusion group (nang6). Serum creatinine and renal tubular necrosis were observed in each group. Human proximal tubular epithelial cell line HK-2 cells were cultured in vitro. The cells were exposed to hydrogen peroxide for 12 h at different concentrations (0. 75 1. 5 mmol/L) and 1. 5 mmol/L hydrogen peroxide to treat HK-2 cells for different time (6? 1212? 24 h),) Cell necrosis was observed under different conditions. After pretreatment with cyclosporine A (CsA) or CypD-siRNA and 1. 5 mmol/L hydrogen peroxide for 12 h, the necrosis of HK-2 cells was observed. Results the level of serum creatinine in ischemia-reperfusion group was significantly higher than that in control group and sham-operation group (P0. 017 and P0. 018). The renal tissue was stained with HE. The proximal tubules in the ischemia-reperfusion group were obviously dilated, the brush margin disappeared, and there were a large number of tubules, vacuolar degeneration and epithelial cell necrosis and exfoliation. There was no renal tissue injury in control group and sham operation group. H_2O_2 stimulated HK-2 cell line in a time-and concentration-dependent manner, with the increase of time and H_2O_2 concentration. The necrosis rate of HK-2 cells increased significantly. Both CypD-siRNA and CypD inhibitor CsA could significantly reduce the cell necrosis induced by H_2O_2 (P0. 026, P0. 008). Conclusion CypD mediates renal tubular epithelial cell necrosis induced by oxidative stress. Inhibition of CypD can improve the survival rate of renal tubular epithelial cells under oxidative stress, thereby reducing the acute renal injury induced by ischemia-reperfusion to some extent.
【作者单位】：华南理工大学医学院;广东省人民医院(广东省医学科学院)肾内科;
【基金】：国家自然科学基金资助项目(编号:81570609,81400738) 广东省自然科学基金资助项目(编号:2014A030313545,2015A030313531)
【分类号】：R692.5

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