N-乙酰半胱氨酸对脑死亡状态巴马小型猪肾脏结构、功能与核转录因子κB表达的影响  

Effects of N-acetylcysteine on the renal structure,function and nuclear factor-kappa B expression in brain-dead Ba-Ma mini pigs

作　　者：郭文治[1] 史冀华[1] 王海蒲[1] 李震[1] 郑守华[1] 张水军[1] 

机构地区：[1]郑州大学第一附属医院外科,河南省郑州市450052

出　　处：《中国组织工程研究与临床康复》2007年第38期7545-7548,共4页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：河南省杰出人才创新基金资助项目(0421002500)~~

摘　　要：目的:观察核转录因子κB活性抑制剂N-乙酰半胱氨酸对脑死亡状态下巴马小型猪肾脏结构、功能与核转录因子κBmRNA及其蛋白表达的影响,以期提高脑死亡供肾的肾移植效果。方法:实验于2003-08/2004-12在河南省实验动物中心及河南省病理学重点实验室完成。①实验分组及方法:将15只巴马小型猪按随机数字表法分为3组(n=5),即脑死亡组、N-乙酰半胱氨酸组及对照组。脑死亡组和N-乙酰半胱氨酸组均应用改进的缓慢间断颅内加压法建立脑死亡模型,脑死亡组不行药物干预;N-乙酰半胱氨酸组分别于初次确认脑死亡后1h,12h给予N-乙酰半胱氨酸。对照组动物麻醉后仅行开颅与开关腹手术。②实验评估:分别于首次判定脑死亡后3,6,12,18和24h检测动物血清中尿素氮、肌酐、白细胞介素1β、白细胞介素6、肿瘤坏死因子α水平。于脑死亡后3,6,12及24h开腹取相同部位肾组织,苏木精-伊红染色后观察肾组织结构变化,应用免疫组化染色观察核转录因子κB蛋白的表达水平,应用反转录-聚合酶链反应法检测核转录因子κBmRNA的动态变化。结果:15只猪均进入结果分析。①自首次判定脑死亡后12h开始,脑死亡组和N-乙酰半胱氨酸组尿素氮和肌酐水平逐渐升高(P<0.05),相同时间点比较N-乙酰半胱氨酸组显著低于脑死亡组(P<0.05)。②自首次判定脑死亡3h开始,脑死亡组及N-乙酰半胱氨酸组白细胞介素1β、白细胞介素6、肿瘤坏死因子α逐渐升高(P<0.05),相同时间点比较N-乙酰半胱氨酸组显著低于脑死亡组(P<0.05)。③自脑死亡后3h开始,脑死亡组及N-乙酰半胱氨酸组肾组织NF-κBmRNA及其蛋白表达水平逐渐升高(P<0.05),相同时间点比较N-乙酰半胱氨酸组显著低于脑死亡组(P<0.05)。④N-乙酰半胱氨酸组和脑死亡组动物脑死亡后12h可见肾脏结构变化,N-乙酰半胱氨酸组变化程度明显轻于脑死亡组。结论:N-乙酰半胱�AIM： To investigate the effects of N-acetylcysteine （NAC） pretreatment, the nuclear factor-κB （NF-κB） active inhibitor, on the renal structure, function and NF-κB mRNA and protein expression in brain-dead Ba-Ma mini pigs, so as to improve the effect of renal transplantation from brain-dead donor. METHODS： The experiment was performed in the Key Laboratory of Pathology in Henan Province and Henan Provincial Experimental Animal Center from August 2003 to December 2004. Fifteen Ba-Ma mini pigs were randomized into 3 groups （n =5）： brain-dead group, NAC pretreatment group, and control group. The brain-dead models were established in brain-dead group and NAC pretreatment group by increasing intracranial pressure in a modified, slow and intermittent way. In addition, NAC group was given NAC treatment at 1, and 2 hours after brain death. Control group was only subjected to craniotomy and laparotomy.（2）At 3, 6, 12, 18 and 24 hours after the initial identification of brain death, serum blood urea nitrogen （BUN）, creatinine （Cr）, intedeukin-1β （IL-1β）, IL-6, and tumor necrosis factor α （TNF-α） were determined. At 3, 6, 12, and 24 hours, the renal tissues of the same part were taken, and the changes of renal tissues were observed by HE staining. The expression of NF-κB protein was observed by immunohistochemistry, and NF-κB mRNA by RT-PCR. RESULTS： Fifteen pigs were involved in the result analysis. （1）Serum BUN and Cr in brain-dead group and NAC group began to increase at 12 hours after the first identification of brain death （P 〈 0.05）, and NAC group was significantly lower than brain-dead group at the same time point （P 〈 0.05）. （2）Since 3 hours after the initial brain death, IL-1β, IL-6, and TNF-α in brain dead group and NAC group began to increase gradually （P 〈 0.05）, and NAC group was significantly lower than brain-dead group at the same time point （P 〈 0.05）. （3）NF-κB mRNA and protein expression in brain-dead group and NAC group b

关 键 词：肾移植 脑死亡 猪 乙酰半胱氨酸 NF—κB 器官移植 

分 类 号：R617[医药卫生—外科学]