竹叶青蛇毒诱导不同品系小鼠系膜增生性肾炎模型的比较研究  

Comparative Research of Murine Habu Snake Venom- induced Glomerulonephritis in Different Mouse Strains

作　　者：文君[1,2] 吴玲玲[1] 涂卫平[3] 崔巧丽[4] 陈大鹏[1] 吕杨[1] 刘晓峦 陈香美[1] 

机构地区：[1]解放军总医院全军肾脏病研究所,肾脏疾病国家重点实验室,国家慢性肾病临床医学研究中心,北京100853 [2]江西省人民医院肾内科,南昌330006 [3]南昌大学第二附属医院肾内科,南昌330006 [4]河南科技大学第一附属医院内分泌科,洛阳471000 [5]天津总医院肾内科,天津300052

出　　处：《中国中西医结合肾病杂志》2014年第12期1043-1046,I0009,共5页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：国家重大科学研究"973"计划项目(No.2011CBA01003);国家自然科学基金资助项目(No.81330019;81270794)

摘　　要：目的:探讨竹叶青蛇毒(habu snake venom,HSV)诱导C57BL/6小鼠和FVB/N小鼠系膜增生性肾炎模型的病理差异,为实验动物模型的选择提供科学依据。方法:取8周龄雄性C57BL/6小鼠(n=33)和FVB/N小鼠(n=52),单次尾静脉注射2.5 mg/kg竹叶青蛇毒建立模型。定期检测血尿素氮和肌酐水平,观察肾组织病理改变并进行病理评分,观察肾小球内PCNA免疫组化染色情况。结果:FVB/N小鼠的存活率(53.2%)明显低于C57BL/6小鼠(89.3%)。肾组织病理表现为C57BL/6小鼠在蛇毒注射后的第1和3天肾小球内出现显著系膜溶解病变,第7天肾小球系膜细胞增殖和系膜基质积聚,第14、21天病变肾小球逐渐恢复正常。FVB/N小鼠注射后第1和3天系膜溶解病变不显著,第7天存在系膜细胞增生,但病变程度低于同期C57BL/6小鼠。病理评分结果示C57BL/6小鼠在模型建立后系膜溶解指数和肾小球硬化指数均高于同期FVB/N小鼠。免疫组化结果显示两种小鼠肾小球内PCNA阳性率在第3、7天均显著高于对照组,其中C57BL/6小鼠肾小球内PCNA表达在第3天高于FVB/N小鼠。结论:静脉注射HSV能诱导小鼠发生系膜增生性肾炎病理改变,C57BL/6小鼠对该模型的耐受性和易感性均优于FVB/N小鼠。Objective：To compare the pathological difference of murine habu snake venom-induced glomerulonephritis be-tween C57BL/6 and FVB/N mice,and to provide researchers with scientific standards for selecting better animal model. Methods：8 weeks old male C57BL/6 mice（n=33）and FVB/N mice（n=52）were used to induce mesangial proliferative glomerulonephritis af-ter a single intravenous injection of habu toxin（2. 5 mg per kg body weight）. Mice were sacrificed on day 1,3,7,14 and 21 after in-jection and blood samples were collected for serum creatinine and urea nitrogen evaluation,and kidneys were harvested for histologic and immunohistochemical studies. PCNA immunohistochemistry was used to observe cell proliferation. Results：The survival rate of FVB/N mice（53. 2%）was lower than that of C57BL/6 mice（89. 3%）. Compared with controls,no significant difference in kidney function was observed in both strains after modeling. The renal pathological results in the C57BL/6 mice group were typical and signif-icant mesangial dissolution could be seen on 1 and 3 days after injection. On day 7,after acute mesangial injury,the lesions of glo-meruli turned into obvious cluster aggregative proliferation,and the glomerular capillary loop disappeared due to the expanded matrix. Segmental sclerosis,global sclerosis and balloon adhesion could be found in some glomeruli. On 14 and 21 days after injection,most of the glomeruli were gradually back to normal. No obvious mesangiolysis was observed throughout the experimental period in the FVB/N mice group after modeling. On day 7 after injection,the mainly changes of the glomeruli were focal mild to moderate prolifera-tion with matrix accumulation which were in lower levels compared with C57BL/6 mice in the same period. The mesangiolysis index score and the glomerulosclerosis index score were remarkablely higher in C57BL/6 mice group compared to FVB/N mice group in the same period. Compared with controls,a statistically significant increase of the PCNA positive rate was obse

关 键 词：竹叶青蛇毒 小鼠系膜增生性肾炎 模型 

分 类 号：R285.5[医药卫生—中药学]