运用两种BSA剂量建立IgA肾病大鼠模型观察

Using Two Kinds of BSA Dose Establish IgA Nephropathy Rats Model Bservation

目的:目前IgA肾病(IgAN)动物模型并无经典造模方法,本实验选择国内较常用方法建立大鼠IgAN模型,分两个时间点观察不同剂量牛血清白蛋白(bovine serum albumin,BSA)灌胃联合注射脂多糖(lipopolysaccharide,LPS)+四氯化碳(carbon terachloride,CCL4)方法建立IgA肾病模型效果。方法:将SPF级健康雄性SD大鼠60只(平均体重200～240g)随机分为3组,每组20只。低剂量组(A组):BSA400mg/kg(100g/L)隔天灌胃,持续12周;皮下注射蓖麻油0.3ml+CCL40.10ml,每周1次持续12周,第8周LPS0.05mg尾静脉注射。高剂量组(B组):BSA增加至600mg/kg(100g/L),余干预同低剂量组。对照组(C组)生理盐水4ml/kg灌胃,0.4ml皮下注射。建模后第8周、12周每组各处死10只大鼠,留取血、尿、肾组织标本检测。观察指标:一般情况、蛋白尿、血尿、肝肾功能、肾组织病理。结果:模型组大鼠血肌酐、尿素氮及尿蛋白均明显增高(P<0.05),高剂量组显著高于低剂量组(P<0.05),且肾组织病理8周后均出现轻中度系膜细胞及系膜基质的增生,12周末显著伴肾间质轻度纤维化,高剂量组病变较重;12周末均有荧光出现,均强于第8周,低剂量组荧光表达不典型,高剂量组表达强于低剂量组(P<0.05)。电镜报告与病理表现一致。结论:运用BSA+LPS+CCL4联合造模方法在12周左右可建立快速IgA肾病动物模型,而且高剂量BSA(600mg/kg)组肾组织病变更显著,模型更典型。此模型的建立及运用可以为IgA肾病临床及基础研究提供良好动物模型基础。

Objective：At present there is no classic method to construct IgAN model in SD rats. To observe IgA nephropa- thy model effect, the experiment divided into two time points at different concentrations bovine serum albumin lavage combined injec- tion lipopolysaecharide ＋ carbon tetrachloride method to establish IgA nephropathy model effect. Methods： Sixty health male SD rats weighing 200 -240 g were randomized into three groups （20 pes/group）. Low dose group （group A）, the rats received oral BSA 400 mg/kg（ 100 g/L）, the next day lavage for 12 weeks, and subcutaneous injection castor oil 0.3 ml add CCL4 0.10 ml, once a week for 12 weeks, 8weeks LPS 0.05 mg caudal vein injection. High dose group （ B）, BSA increased to 600 mg/kg （ 100 g/L） in ad- dition to the above treatments. Results： Control group （ C）, to physiological saline 4 ml/kg lavage, subcutaneous injection 0.4 ml physiological saline, frequency with model group. Ten rats were sacrificed respectively in every group at the end of week 8 and 12, the blood, urine, kidney tissue samples were examined. The observation index：general situation, proteinuria, hematuria, kidney and liv- er function, renal tissue pathology. Conclusion： Model rats, serum creatinine, blood urea nitrogen and urinary protein were signifi- cantly higher（ P 〈 0.05 ）, and high dose group is significantly higher than low dose group（P 〈 0.05）. Model group renal tissue patho- logical 8 weeks after all appear mild -to -moderate mesangial cells and mesangial matrix hyperplasia, 12 weekend significantly with renal interstitial mild fibrosis, high dose group of lesions heavier;l 2 weekend model group all have fluorescent appear, and better than 8 weeks, low dose group of fluorescence expression is not typical, high dose group expression than low dose group （P 〈 0.05 ）. Elec- tron microscopy （sere）report and pathology in performance. Conclusion： Joint the method of BSA ＋ LPS ＋ CCL4 in 12 weeks can build successful IgA nephrupathy animal models kidney tissue pathological changes more significant, model more typical.