维生素E对大鼠肾脏缺血再灌注损伤诱导的肾小管上皮细胞凋亡的影响

Vitamin E inhibits renal ischemia/reperfusion injury-induced tubular cell apoptosis

目的探讨维生素E对大鼠肾脏缺血再灌注损伤(IRI)诱导的肾小管上皮细胞凋亡的影响及可能的机制。方法健康雄性Wistar大鼠18只随机分为对照组、IRI组和维生素E组。动物右肾切除1周后,夹闭左肾动脉制作IRI模型,24h后取肾标本,维生素E组右肾切除后给予维生素E50mg/d灌胃至再灌注24h。半定量分析肾脏病理损伤、TUNEL检测肾组织凋亡、比色法测肾组织caspase-3活性。结果①与对照组相比,IRI组肾脏病理损伤严重、肾小管上皮细胞凋亡明显增加、caspase-3活性明显增高(P<0.01);②与IRI组相比,维生素E处理组肾脏病理损伤明显减轻、肾小管上皮细胞凋亡明显减少、caspase-3活性明显减少(P<0.01)。结论维生素E能抑制肾脏IRI诱导的肾小管上皮细胞凋亡,其机制可能是通过抑制caspase依赖的细胞凋亡途径实现的。

Objective To investigate the inhibitive effect of vitamin E on renal ischemia/reperfusion injury-induced tubular cell apoptosis and its mechanisms. Methods Eighteen male Wistar rats were randomly divided into three groups：control group,IRI group and vitamin E group.After removal of right kidney for 1 week,the IRI model was established by clamping the left renal arteries.Kidney samples were harvested at 24 h after reperfusion.Rats in vitamin E group were gavaged with vitamin E（50 mg/d）after the left renal clamping until reperfusion for 24 h.The morphological changes of renal tissues were observed by periodic acid-Schiff（PAS）staining.Tubular cell apoptosis was confirmed by terminal deoxynucleotidyl transferase meditated dUTP-biotin nick end labeling（TUNEL）assay.Caspase-3 activity was determined by a colorimetric method. Results ①Compared with control group,kidneys displayed a severer pathological injuries in IRI group,and the apoptotic cells and the activity of caspase-3 increased significantly（P0.01）.②Compared with IRI group,renal histopathology injuries significantly attenuated in vitamin E group.Apoptotic tubular cells and caspase-3 activity decreased after pretreatment with vitamin E（P0.01）. Conclusion Pretreatment with vitamin E could inhibit the IRI-induced tubular cell apoptosis,which may,at least partly,be the result of the inhibition of the caspase-dependent pathway.