褪黑素在急性肾缺血再灌注损伤中的防治作用及其对细胞凋亡的影响  

THE PROTECTIVE EFFECT OF MELATONIN IN ACUTE ISCHEMIA REPERFUSION RENAL INJURY

作　　者：陈敏[1] 郭仁寿[1] 陈重义[1] 张龙江[1] 许家琪[1] 余立平 

机构地区：[1]湖北医科大学附属第二医院儿科,武汉430071

出　　处：《肾脏病与透析肾移植杂志》1999年第1期27-30,共4页Chinese Journal of Nephrology,Dialysis & Transplantation

摘　　要：目的：探讨急性肾缺血再灌注损伤（ ＡＲⅠ） 的机制及其与细胞凋亡的关系以及褪黑素（ ＭＥＬ） 对ＡＲⅠ的保护作用。　方法：用动脉夹夹闭大鼠双侧肾蒂４５ ｍｉｎ 再灌注２４ｈ 的手术方法制成ＡＲ Ⅰ动物模型，将动物分为假手术对照组、手术组、维生素Ｃ 预防组、ＭＥＬ 不同剂量预防组，动态检测血尿素氮（ＢＵＮ） 、肌酐（Ｃｒ） 、超氧化物歧化酶（ＳＯＤ） 、谷胱甘肽过氧化物酶（ＧＳＨＰｘ） 、丙二醛（ ＭＤＡ） 、肾组织光镜、电镜形态学观察及ＤＮＡ 电泳分析。结果：手术组ＢＵＮ、Ｃｒ 升高、ＳＯＤ、ＧＳＨＰｘ 下降，ＭＤＡ 上升，形态学显示肾小管细胞发生凋亡。ＭＥＬ 预防用药能不同程度地逆转上述改变，防止凋亡的发生，效应呈剂量依赖性，且较已知的抗氧化剂作用更明显。　结论：氧自由基（ＯＦＲ） 是ＡＲⅠ的主要机制之一，ＡＲⅠ确实存在着细胞凋亡的病理改变。ＭＥＬ 预防用药能减轻ＡＲⅠ，减少细胞凋亡的发生，效应呈剂量依赖性。OBJECTIVE To investigate the protective effects of melatonin in acute ischemia reperfusion renal injury in rat model. METHODOLOGY A rat model of acute ischemia reperfusion renal injury was established by bilateral renal pedical occlusion for 45 minutes followed by reperfusion for 24 hours in SD rats.Rats in the treatment groups were administered with melatonin(0 3 mg/kg,0 95 mg/kg,3 0 mg/kg)30 minutes prior to operation.This study was controlled with sham operation group,operation group,and vitamin C administered group.Blood urea nitrogen(BUN),serum creatinine(Cr),blood superoxide dismutase(SOD),glutathoine peroxiase(GSH Px)and malondialdehyde(MDA)were determined.Apoptosis was detected by both light and electron microscopy.Agarose gel electrophoresis of DNA isolated from rats′kidney was analyzed. RESULTS (1)As compared to the sham operation group,BUN,Cr and MDA were significantly increased,while SOD and GSH Px were decreased in the operation group.Pathological changes of apoptosis and typical “ladder pattern”of 180 200bp DNA fragments were observed in the operation group.(2)As compared to the operation group and vitamin C administered group,the changes of BUN,Cr,MDA,SOD and GSH Px were reversed to some degrees in a dose dependent manner.The numbers of apoptotic cells were less in the melatonin groups than that of the operation group.No “ladder pattern”of in the gel electrophoresis of DNA was found in the treatment groups. CONCLUSION Free oxygenate radicals may be involved in renal tubular cell apoptosis in the acute ischemia reperfusion renal injury model.Melatonin protects the kidney from acute ischemia reperfusion renal injury through a mechanism in which renal tubular cell apoptosis is reduced.The protective effect of melatonin is dose dependent and greater t

关 键 词：急性 再灌注损伤 细胞凋亡 褪黑素 肾缺血 

分 类 号：R692.01[医药卫生—泌尿科学] R977.1[医药卫生—外科学]