X线造影剂对高胆固醇血症大鼠的肾毒性及己酮可可碱的保护作用  

Nephrotoxicity of X-ray contrast media and protective effect of pentoxifylline in rats with hypercholesterolemia

作　　者：李英娟[1] 段绍斌[1] 周晓蓉[1] 王予慧[1] 李军[1] 彭佑铭[1] 刘伏友[1] 

机构地区：[1]中南大学肾病研究所湖南省肾脏病与血液净化重点实验室中南大学湘雅二医院肾内科 ,长沙410011

出　　处：《中华肾脏病杂志》2008年第10期730-735,共6页Chinese Journal of Nephrology

基　　金：湖南省科委社会发展基金（1013-98）

摘　　要：目的比较不同渗透浓度X线造影剂对高胆同醇血症大鼠的肾毒性，探讨已酮可可碱（PTX）对造影剂肾毒性是否有保护作用。方法48只健康雄性SD大鼠，随机分为正常饮食组8只（NN组）和高胆同醇饮食组40只（H组，4％胆同醇±1％胆酸钠）。8周末，高胆固醇饮食组随机分为5组，每组8只，分别为高胆同醇饮食组（HN组）、高胆旧醇±低渗造影剂组（HL组）、高胆同醇±等渗造影剂组（HI组）、高胆固醇饮食±高渗造影剂组（HH组）、高胆固醇±高渗造影剂±PTX组（HHP组）。在注射造影剂后48h测定各组大鼠的血清总胆同醇、三酰甘油、血清肌酐、内生肌酐清除率（Ccr）、钠钾排泄分数及血管紧张素Ⅱ（AngⅡ）的浓度；光镜下观察肾组织学改变；免疫组化法检测肾组织NF—κB的蛋白表达；原位细胞调亡（TUNEL）染色检测肾小管上皮细胞的捌亡。结果所有给了高胆同醇饮食的火鼠血清总胆固醇水平明显增高（P〈0．05）。HH组的血清肌酐、钠钾排泄分数及血浆AngⅡ水甲均分别明显高于HHP组、HL组及HI组（P〈0．05）；HH组Ccr水平[（0．11±0．02）ml·min^-1·（100g）^-1]则明显低于HHP组[（0．43±0．03）mml·min^-1·（100g）^-1]、HL组[（0．25±0．02）ml·min^-1·（100g）^-1]和HI组[（0．27±0．03）ml·min^-1·（100g）^-1]（P〈0．05）。组织病理显示，HH组大鼠肾小管上皮细胞发生明显的变性和坏死，肾小管卜皮细胞凋亡率（89．60％±6．40％）明显高于其他各组[NN组（2．40％±0．77％）、HN组（5．60％±1．08％）、HHP组（8．91％±1．44％）、HL组（63．34％±11．97％）、HI组（61．50％±9．40％）]（P〈0．05）。肾组织NF—κB阳性细胞的平均灰度值明显低于其他各组（P〈0．05）；而HL组和HI组间上述指标比较差异无统计学意义（P〉0．05）。结论高胆同醇血症环境下注射不同渗透浓度X线造�Objective To evaluate the nephrotoxicity induced by radiographic contrast media with different osmolality in rats with hypereholesterolemia, and to explore the protective effect of pentoxifylline. Methods Forty-eight healthy SD male rats were randomly divided into normal dietary group （NN, n =8） and high cholesterol supplemented dietary group （H, 4% cholesterol and 1% eholic acid, n=40）. At the end of 8th week, the rats with high cholesterol diet were randomly divided into five subgroups （n=8, respectively）： high cholesterol diet group（HN）, high cholesterol plus iso-osmolar contrast media （iodixanot, IOCM） group （HI）, high cholesterol plus low-osmolar contrast media （iohexle, LOCM） group （HL）, high cholesterol diet plus high-osmolar contrast media （diatrizoate, HOCM） group （HH） and high cholesterol plus HOCM plus pentoxifylline group （HHP）. Forty-eight hours after contrast media injection, the rats were executed and blood samples were prepared to determine total cholesterol, triglyceride, serum ereatinine, creatinine elearance（Cer）, fractional excretion of sodium and potassium（FeNa, FeK）, and angtension Ⅱ （And Ⅱ） levels. The renal injury was assessed bv HE staining and TUNEL staining, respectively. The expression of NF-κB protein in the renal tissue was detected by using immunohistochemieal method. Results An increase of cholesterol was observed in all the rats with high cholesterol diet. Scr, FeNa%, FeK% and Ang Ⅱ levels of rats in HH group were obviously higher than those in HL and HI groups respectively. Ccr in HH group [（0.11±0.02） ml·min^-1 （100 g）^-1] was significantly lower than that in HHP gruup [（0.43±0.03） ml·min^-1（100 g）^-1], HL group [（0.25±0.02）ml·min^-1（100 g）^-1] or HI group [（0.27 ±0.03）ml·min^-1（100 g）^-1] （P〈0.05）. TUNEL staining showed that the percentage of apoptotic cells in HH group [（89.60±6.40）%] was higher than that of the other groups INN （2.40±0.77）%, HN （5.60±1.0

关 键 词：造影剂 高胆同醇血症 己酮可可碱 肾毒性 细胞凋亡 

分 类 号：R96[医药卫生—药理学]