机构地区:[1]福建医科大学附属协和医院肾内科,福建福州350001 [2]福建省临床免疫研究所
出 处:《中华高血压杂志(中英文)》2024年第10期941-947,共7页Chinese Journal of Hypertension
基 金:国家自然科学基金面上项目(82070727);福建省自然科学基金面上项目(2020J011024)。
摘 要:目的 探讨C57BL/6不同亚型对阿霉素肾毒性的易感性差异,为C57BL/6菌株阿霉素肾病模型的构建提供相应的理论数据。方法 24只雄性C57BL/6J、24只雄性C57BL/6N小鼠均随机分组成模型组(阿霉素15 mg/kg,一次性尾静脉注射)和对照组,24只雄性BALB/c小鼠随机分组成模型组(阿霉素10 mg/kg,一次性尾静脉注射)和对照组,对照组均一次性尾静脉注射等量生理盐水。在造模后0、2、4、6周留取24 h尿液检测各组尿蛋白/肌酐比;2周及6周时收获各组小鼠,检测血白蛋白、总胆固醇、尿素及肌酐;观察各组肾组织病理形态。结果 C57BL/6J、C57BL/6N模型组不同时间段的尿蛋白/肌酐比与对照组差异无统计学意义(均P>0.05),且两种亚型小鼠造模2周及6周时的肾功能、血白蛋白及总胆固醇水平与对照组比较差异亦无统计学意义(P>0.05),而BALB/c小鼠2周时模型组尿蛋白/肌酐比和血白蛋白水平与对照组比较,差异有统计学意义[尿蛋白肌酐比:24.00±1.35比5.95±1.18,P<0.01;血白蛋白:(19.85±3.16)比(27.32±2.07)g/L,t=3.43,P=0.02]。病理形态学上,C57BL/6J和C57BL/6N模型组小鼠2周及6周时的肾小球、肾小管及间质形态基本正常,模型组肾小球硬化指数及小管间质损伤评分与对照组比较差异无统计学意义(P>0.05),而BALB/c小鼠模型组2周时可见肾小球局灶节段性硬化、肾小球系膜基质增多、蛋白管型可见,肾间质散在炎症细胞浸润,6周时病理损伤加重。结论 一次性尾静脉注射阿霉素15 mg/kg时,C57BL/6J和C57BL/6N两种亚型小鼠对阿霉素肾毒性无明显易感性。Objective To investigate whether there were differences in susceptibility to adriamycin(ADR) nephropathy in C57BL/6 substrains,and to provide theoretical data for the construction of adriamycin nephropathy model of C57BL/6 strains.Methods Twenty-four male C57BL/6J and 24 male C57BL/6N mice were randomly divided into model group(adriamycin 15 mg/kg,single injection through tail vein) and control group,24 male BALB/c mice were also randomly divided into model group(adriamycin 10 mg/kg,single injection through tail vein) and control group.All control groups were injected with the same amount of normal saline through the tail vein.After 0,2,4 and 6 weeks of modeling,urine samples were collected for 24 hours to detect urine protein/creatinine ratio in each group.After 2 weeks and 6 weeks,the mice were harvested and the blood albumin,total cholesterol,urea and creatinine were detected,and renal pathology in each group was observed.Results There was no significant difference in urinary protein/creatinine ratio between C57BL/6J and C57BL/6N ADR groups and control groups(P>0.05).There was also no significant difference in renal function,albumin and total cholesterol levels between ADR and control groups for the two substrains at 2 weeks and 6 weeks(P>0.05).While in BALB/c mice,the urinary protein/creatinine ratio and blood albumin were significantly different from those in the control group at 2 weeks after modeling [urinary protein/creatinine ratio:24.00±1.35 vs 5.95±1.18,P<0.01;blood albumin:(19.85±3.16) vs(27.32±2.07) g/L,t=3.43,P=0.02].In renal pathology,the glomerular,tubular and interstitial morphology of mice in C57BL/6J and C57BL/6N groups were basically normal,and there was no statistical difference in glomerular sclerosis index and tubule interstitial injury score at 2 weeks and 6 weeks with the control group(P>0.05).While in BALB/c mice,focal segmental sclerosis,mesangial matrix of the glomerulus and protein tubule pattern were observed at 2 weeks,and inflammatory cell infiltration was observed in renal tub
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