改良大鼠IgA肾病模型建立及氧化应激状态评估  

Establishment of modified IgA nephropathy rat model and assessment of oxidative stress

作　　者：高明[1] 张连栋[2] 张莉[1] 王昌[1] 卢燕 GAO Ming;ZHANG Lian-dong;ZHANG Li;WANG Chang;LU Yan(Department of Nephrology , Xi＇ an No. 4 Hospital, Xi＇an 710003, China)

机构地区：[1]西安市第四医院肾内科,710003 [2]西安交通大学第二附属医院泌尿外科,710004 [3]解放军第306医院航天城门诊部

出　　处：《临床肾脏病杂志》2018年第4期243-247,共5页Journal Of Clinical Nephrology

基　　金：陕西省自然科学基金项目(No.2016SF-118)

摘　　要：目的对原有Ig A肾病(Ig AN)模型进行改进,并评估该模型肾脏氧化应激状态改变,为探索Ig AN模型建立方法提供实验依据。方法取SPF级SD雌性大鼠12只,体质量200～240 g,采用随机数字表法随机分为正常对照组(C组)及改良模型组(M组)。C组生理盐水4 ml/kg灌胃,皮下注射生理盐水0.4 ml;M组采用牛血清白蛋白600 mg/kg隔日灌胃+皮下注射四氯化碳0.10 ml、蓖麻油0.3 ml及胸腺肽3 mg+尾静脉注射脂多糖0.05 mg建立模型,观察至第12周末,分别观察2组大鼠一般状态、检测2组血肌酐(SCr)、尿素氮(BUN)、白蛋白(Alb)并测定24h尿蛋白定量,肾脏组织行Ig A免疫荧光、苏木素-伊红(HE)染色并评估肾脏组织氧化应激状态。结果 M组大鼠均出现精神萎靡、倦卧少动、毛发稀疏等状况。M组BUN、SCr较C组显著升高(P<0.05),Alb水平较C组显著降低(P<0.01);24 h尿蛋白定量较C组显著升高(P<0.05)。M组大鼠肾脏系膜区Ig A团块样沉积,HE染色M组可见肾小球系膜区轻度增宽,偶见中度增宽,系膜细胞及基质增多。M组肾脏组织超氧化物歧化酶、总抗氧化能力水平较C组均显著下降(P<0.05),丙二醛水平显著高于C组(P<0.05)。结论改良大鼠Ig AN模型造模效果良好,生化及病理指标与人Ig AN类似,肾脏氧化应激状态改变是该过程中重要的机制之一。Objective To modify the traditional Ig A nephropathy model and evaluate the oxidative stress status of the model,providing experimental evidence for the establishment of Ig A nephropathy animal model. Methods Twelve female SPF SD rats weighing 200-240 g were randomly divided into normal control group(group C） and modified model group(group M） according to the random digital table method. The animals in group C were gavaged with normal saline at 4 ml/kg and given subcutaneous injection at 0. 4 ml,and those in group M were treated with bovine serum albumin at 600 mg/kg every day by gavage,and subcutaneously injected with carbon tetrachloride at 0. 10 ml,castor oil at 0. 3 ml,thymosin at 3 mg and LPS at 0. 05 mg. At the 12 th week,the general states of rats in two groups were observed. Serum creatinine(SCr）,blood urea nitrogen(BUN）,albumin(Alb） and 24-h urine protein were determined. Ig A immunofluorescence,HE staining,biochemical index as well as the state of oxidative stress in the kidney were evaluated. Results All the rats in the group M suffered from mental depression,tiredness,decreased movement and sparse hair. BUN and SCr levels in group M were significantly higher(P〈 0. 05）,the level of Alb was significantly lower(P 〈0. 01）,and 24-h urine protein was significantly higher than those in group C(P〈 0. 05）. In group M,Ig A clumps were de-posited in the renal mesangial region,the glomerular mesangial area was slightly widened,even moderately broadened,and increased mesangial cells and matrix were observed by HE staining. The levels of SOD and T-AOC in renal tissue of group M were significantly lower(P 〈0. 05）,and the level of MDA was significantly higher than that of group C(P〈 0. 05）. Conclusions The modified Ig A nephropathy rat model is optimal,and the biochemical and pathological indexes are similar to those of human Ig A nephropathy. The change of oxidative stress in the kidney is one of the important pathological mechanisms involved in the process.

关 键 词：IGA肾病 动物模型 氧化应激 

分 类 号：R-332[医药卫生] R692.6