反向模式钠钙离子交换体抑制剂降低造影剂诱导的肾小管上皮细胞凋亡  

Reverse mode of Na^＋/Ca^2＋ exchange inhibitor, KB-r7943 attenuates tubular epithelial cell apoptosis induced by contrast media

作　　者：杨定平[1] 贾汝汉[1] 丁国华[1] 杨定位[2] 熊晓玲[1] 

机构地区：[1]武汉大学人民医院肾内科,武汉430060 [2]天津医科大学总医院肾内科

出　　处：《中华急诊医学杂志》2008年第7期713-716,共4页Chinese Journal of Emergency Medicine

基　　金：湖北省自然基金资助项目（2007ABA254）

摘　　要：目的探讨反向模式钠钙离子交换体抑制剂KB-R7943是否对造影剂肾损伤具有保护作用。方法培养大鼠肾小管上皮细胞分别与不同浓度KB-R7943（10^-5，10^-6 mol／L）作用12h后，加入造影剂作用1h，采用LDH检测细胞损伤，倒置显微镜观察细胞形态变化，流式细胞仪检测细胞凋亡，共聚焦显微镜测定细胞内钙和反应氧产物水平，RT-PCR检测钠钙离子交换体mRNA表达。相同渗透压甘露醇作对照。数据以均数±标准差（x±s）表示，统计采用方差分析和q检验，简单直线相关分析两者相关性，以P〈0．05为差异具有统计学意义。结果造影剂作用1h诱导了明显细胞损伤和细胞凋亡，细胞内钙和反应氧产物增加，KB-R7943降低了细胞内钙和反应氧产物水平，同时降低了细胞损伤和细胞凋亡并呈剂量效应；钠钙离子交换体mRNA表达无变化。结论KB-R794对造影剂诱导的肾小管上皮细胞损伤具有保护作用。Objective To investigate the renoprotective effects of KB-R7943 on renal injury induced by contrast media. Method Tubular epithelial cells were treated with various concentration of KB-R7943 （10^-5, 10^-6 moL/L） for 12 hours before contrast media was used. After cells were incubated with contrast media （CM） （110 mgI/L） for 1 hour, cells injury was assessed by using LDH, and cell morphologic changes and cells apoptosis were evaluated with inverted microscope and flow cytometry, respectively. Intracellular Ca^2＋ and reactive oxy- gen species （ROS） were analyzed by using confocal microscope. The expression of Na^＋/Ca^2＋ exchanger mRNA was evaluated by RT-PCR. Mannitol with same osmolarity （20% mannitol, 770 mOsm/L） of CM was used as control. One-way analysis of variance and q-test were used for comparison between groups. The simple linear correlation was employed to analyze the correlation. P 〈 0.05 was considered significant. Results Contrast media significantly induced tubular cells damage significantly and apoptosis at 1 hour after incubation, meanwhile, intracellular Ca^2＋ and ROS were increased progressively in CM group. KB-R7943 significantly attenuated cells damage and apoptosis in dose-dependent in association with decreased intracellular Ca^2＋ and ROS. Expression of Na^＋/Ca^2＋ exchanger mRNA was not changed. Conclusion KB-R7943 has renopretective effects on the contrast-media-induced renal tubular cyotoxicity.

关 键 词：造影剂 细胞凋亡 钙离子交换体抑制剂 

分 类 号：R692[医药卫生—泌尿科学]