Effect of fenoldopam on ischemia/reperfusion-induced apoptosis

被引:15
作者
Aravindan, Natarajan [1 ]
Cata, Juan P. [1 ]
Dougherty, Patrick M. [1 ]
Shaw, Andrew D. [1 ]
机构
[1] Univ Texas, MD Anderson Canc Ctr, Div Anesthesiol & Crit Care, Unit 112, Houston, TX 77030 USA
关键词
fenoldopam; ischemia/reperfusion; apoptosis; microarray; acute renal failure; rat kidney;
D O I
10.1080/08860220600583690
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Recently we demonstrated the effect of fenoldopam on ischemia/reperfusion (I/R) induced NF kappa B mediated pro-inflammatory signal transduction. However, the effect of fenoldopam on I/R-induced apoptosis is not known. We utilized a rat model of acute ischemic nephropathy to test the hypothesis that fenoldopam attenuates I/R-induced apoptosis. Sprague-Dawley rats were anesthetized by intraperitoneal administration of 50 mg/kg urethane and randomly allocated into 4 groups (n = 6 each): 1) sham-operated, 2) sham operation with infusion of 0.1 mu g/kg/min fenoldopam, 3) unilateral renal ischemia followed by 4 h of reperfusion, and 4) I/R with fenoldopam infusion. Kidney samples were fixed and paraffin-embedded to measure apoptosis. Data were compared between groups using ANOVA with Bonferroni correction. RNA was extracted from each left kidney to probe cDNA microarray and measure gene expression as percent of positive control. Compared to the control group, I/R significantly (P < 0.001) induced apoptosis in both the cortex and medulla. Similarly, microarray analysis revealed that I/R induced 73 apoptosis-related genes. Treatment with fenoldopam significantly reduced (P < 0.001) I/R-induced apoptosis both in the cortex and medulla and attenuated all 73 I/R-induced apoptosis-related genes. Data from this rat model of ischemic nephropathy suggest that fenoldopam may attenuate I/R-induced apoptosis and apoptosis-related gene transcription.
引用
收藏
页码:337 / 344
页数:8
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