一氧化氮在阿霉素肾病大鼠发病中的作用和机制  

The effect and mechanism of nitric oxide in rats with adriamycin-induced nephropathy

作　　者：李树全[1] 阳冠明[1] 韦勇 

机构地区：[1]广西医科大学第一附属医院儿科,南宁530021 [2]广西南宁区江滨医院检验科

出　　处：《肾脏病与透析肾移植杂志》2001年第6期532-538,共7页Chinese Journal of Nephrology,Dialysis & Transplantation

基　　金：广西自然科学基金 (NO :982 40 0 1)资助

摘　　要：目的 :探讨一氧化氮 (NO)在阿霉素 (ADR)肾病病鼠发病中的作用及其机制。　 方法 :复制阿霉素肾病模型 ,分别用L 精氨酸 (L Arg)及N 硝酸 L 精氨酸甲基酯 (L NAME)进行干预 ,用硝酸还原酶法测定肾皮质匀浆NO代谢产物NO-2 /NO-3 水平来反映NO水平 ,用末端标记法和免疫组化法分别检测皮质部细胞凋亡和Bcl 2、Bax、c Myc蛋白表达情况 ,用原位杂交法测定皮质部细胞p5 3 mRNA转录水平。　 结果 :　①ADR组肾皮质匀浆NO-2 /NO-3 水平明显低于对照组 (P <0 0 1) ,皮质部细胞凋亡数、p5 3 mRNA水平和c Myc蛋白表达均分别明显高于对照组 (P均小于 0 0 1) ,肾小管细胞Bcl 2蛋白表达明显低于对照组而Bax蛋白表达却明显高于对照组 (P均小于0 0 1)。②ADR +L Arg组肾皮质匀浆NO-2 /NO-3 水平明显高于ADR组 (P <0 0 1) ,皮质部细胞凋亡数、p5 3 mRNA水平和c Myc蛋白表达则分别明显低于ADR组 (P均小于 0 0 5 ) ,肾小管细胞Bcl 2蛋白表达明显高于ADR组而Bax蛋白表达则明显低于ADR组 (P均小于 0 0 5 )。③ADR +L NAME组肾皮质匀浆NO-2 /NO-3 水平明显低于ADR组(P <0 0 1) ,皮质部细胞凋亡数、p5 3 mRNA水平和c Myc蛋白表达均明显高于ADR组 (P均小于 0 0 5 ) ,肾小管细胞BclObjective:To investigate the effect and mechanism of nitric oxide(NO) in rats with adriamycin-induced nephropathy. Methodology:Forty male Wistar rats were divided into 4 groups:Control,ADR,ADR+L-Arg and ADR+L-NAME groups.Adriamycin(7 0 mg/kg)was injected in the tail veins of the ADR,ADR+L-Arg and ADR+L-NAME groups respectively.Meanwhile,the control groups was injected an equal volume of saline.The ADR+L-Arg group was given intraperitoneal injection of L-arginine(100 mg/kg·d -1 )and the ADR+L-NAME group,received intraperitoneal injection of N-nitro-L-arginine methylester(L-NAME)(5 mg/kg·d -1 ).All rats were sacrificed on the 28 th day after the first injection.Their kidneys were examined by light and electric microscopy.The level of NO - 2/NO - 3 was detected by nitric acid reductase method.Apoptotic cells were analyzed by in situ terminal deoxymudeotidyl trasferase(TDT)mediated nick end-labeling.The level of p53 mRNA was determined by in situ hybridization.The expression of Bcl-2,Bax and c-Myc were examined by immunocytochemistry method. Results:①In ADR group,the level of renal cortex NO - 2/NO - 3 was significantly lower than of control ( P <0 01).However,the number of apoptotic cells,expression of c-Mye and level of p53-mRNA in glomeruli and tubule were significantly higher than that of control ( P <0 01).The expression of Bcl-2 in tubule was significantly decreased,while the expression of Bax was significantly increased compared with that of control ( P <0 01).②In ADR+L-Arg group,the level of renal cortex NO - 2/NO - 3 was significantly higher than that of ADR ( P <0 01).The number of apoptotic cells,expression of c-Mye and the level of p53-mRNA in glomeruli and tubule was significantly lower than that of ADR ( P <0 05).The expression of Bcl-2 in tubule was significantly increased ( P <0 05),while the expression of Bax was significantly decreased compared with that of control ( P <0 05).③In L-NAME group,the level of renal cortex NO - 2/NO - 3 was

关 键 词：肾病 一氧化氮 细胞凋亡 

分 类 号：R692.9[医药卫生—泌尿科学]