适合治疗给药的大鼠抗肾小球基底膜肾炎模型的建立与应用  

Methodology establishment and application of therapeutic treatment on rats with anti-glomerular basement membrane nephritis

作　　者：石祖胶 陈芙蓉[2] 姜溪[2] 只德广[2] 岳南[2] 孙双勇[2] 

机构地区：[1]贵州省人口和计划生育科学研究技术指导所,贵州贵阳550004 [2]天津药物研究院新药评价有限公司,天津300300

出　　处：《中草药》2017年第17期3568-3574,共7页Chinese Traditional and Herbal Drugs

摘　　要：目的建立适合治疗给药的大鼠抗肾小球基底膜(GBM)肾炎模型。方法采用家兔多点sc大鼠肾小球基底膜与弗氏佐剂乳化物的方法进行免疫,两周1次,共5次,制备抗血清;分次给大鼠iv抗血清,检测血清循环免疫复合物(CIC)水平、肾小球基底膜免疫荧光强度、肾脏及肾小球基底膜病变,确定适合治疗给药的抗血清效价、免疫剂量、方式及时间。以固肾2号为治疗药物,验证模型的可行性。结果使用效价为1∶4的兔抗大鼠GBM血清4 m L,分3 d 4次iv免疫,免疫第6、8、10天,均能形成大鼠抗肾小球基底膜肾炎,免疫第6天,病变相对较轻,免疫第8天及第10天,病变基本稳定。验证实验结果显示,连续给药30 d,固肾2号显著降低模型大鼠24 h尿蛋白排出,减轻肾脏病变,对大鼠抗肾小球基底膜肾炎有明显治疗作用。结论使用效价为1∶4的兔抗大鼠GBM血清4 m L,分3 d 4次iv免疫,免疫后8 d,能形成适合治疗给药的大鼠抗肾小球基底膜肾炎模型。Objective To establish a suitable model for therapeutic treatment on rats of anti-glomerular basement membrane nephritis. Methods Rabbit with rat glomerular basement membrane and freund＇s adjuvant were immuned by multi-point subcutaneous injection biweekly, five times totally, and the antiserum was prepared. Experimental model for therapeutic treatment was established. Serum level of immune complex（CIC）, intensity of immunofluorescence of glomerular basement membrane, lesion of kidney and glomerular basement membrane was measured by multiple intravenous injection of antiserum to rats to determine suitable experiment conditions including titer of antiserum, dose of antiserum, method and time of antiserum injection. The model was observed the efficacy using Gushen 2 as therapeutic drug. Results Rats with 4 m L antiserum（titer 1∶4） by intravenous injection were immuned 4 times 3 d. Rat anti-glomerular basement membrane nephritis form on day 6, 8, and 10 since immunization; Pathogenic condition were relatively mild on day 6 since immunization and basically stable on day 8 and 10 since immunization. Verification tests showed that, Gushen 2 significantly reduced the 24 h urine protein excretion, relieved kidney lesion for 30 consecutive days, which had obvious therapeutic effect on rats with anti-glomerular basement membrane of nephritis. ConclusionRats immuned with 4 m L antiserum（titer 1∶4） by intravenous, immune points up to 4 times 3 d, rat anti-glomerular basement membrane nephritis model form which are suitable for therapeutic treatment of drug on day 8 since immunization.

关 键 词：抗肾小球基底膜肾炎 固肾2号 尿蛋白 免疫荧光 抗血清效价 

分 类 号：R285.51[医药卫生—中药学]