小鼠肥胖相关性肾病模型的建立与探索  

Establishment and exploration of an obesity-related glomerulopathy mouse model

作　　者：胡虎 朱丹 王雅茹 曾怡 徐莹 李佳川[1] HU Hu;ZHU Dan;WANG Yaru;ZENG Yi;XU Ying;LI Jiachuan(School of Pharmacy and Food,Southwest Minzu University,Chengdu 610041,China;Department of Endocrinology and Nephrology,363 Hospital,Chengdu 610065,China)

机构地区：[1]西南民族大学药学与食品学院,四川成都610041 [2]通用集团三六三医院内分泌肾内科,四川成都610065

出　　处：《西南民族大学学报(自然科学版)》2025年第2期160-165,共6页Journal of Southwest Minzu University(Natural Science Edition)

基　　金：中央高校基本科研业务费专项(ZYN2024076);通用医疗科研基金项目(TYYLKYJJ-2023-024、TYYLKYJJ-2024-023);四川省自然科学基金项目(2024NSFSC0597);成都市卫生健康委课题(2022547、2023268)。

摘　　要：研究结合肥胖相关性肾病(ORG)发病机制,分别考察不同造模因素(高脂饲料、高脂饲料+阿霉素)和造模周期(16 w和24 w)对C57BL/6J小鼠ORG模型建立的影响,并进行验证性试验.实验结果表明,单纯性给予60%高脂饲料连续16 w能较好造成小鼠肥胖模型,而阿霉素复合造模后,虽然小鼠微量尿蛋白和肾功能损伤更为明显,但是体重明显降低,不符合肥胖标准;同时,将小鼠造模时间延长至24 w后,ORG模型小鼠成模率明显提升,小鼠尿液mALB及ACR比值均明显增加,体质量及肥胖相关指数BMI、Lee′s指数和FI也均明显增升高.验证试验也表明,造模24 w后,模型小鼠均出现典型的糖脂代谢异常和肾功能损伤,小鼠血清FBG、TC、TG、LDL-C、NEFA、BUM和SCr明显升高,HDL-C显著降低,OGTT试验显示糖耐量异常;小鼠肾组织病理形态学以及近曲小管上皮细胞超微结构也均显示出异常,模型动物病理特征明显.因此,采用60%高脂饲料连续喂养C57BL/6J小鼠24 w可建立较稳定的ORG动物模型,该模型能较好模拟人类肥胖相关性肾病的发病因素及病理特征.Based on the pathogenesis of obesity-related glomerulopathy(ORG),this study systematically evaluated the effects of distinct modeling strategies-high-fat diet(HFD)alone versus HFD combined with adriamycin(ADR)-and modeling durations(16 vs.24 weeks)on the establishment of ORG in C57BL/6J mice,with subsequent validation experiments.The results revealed that 16-week continuous feeding with a 60%HFD effectively induced obesity in mice.However,while the ADR-combined group displayed exacerbated microalbuminuria and renal dysfunction,it exhibited paradoxical weight reduction below obesity thresholds.Extending the modeling duration to 24 weeks significantly enhanced ORG model fidelity,as evidenced by elevated urinary microalbumin(mALB)and albumin-to-creatinine ratio(ACR),alongside increased body weight and obesity-associated indices(body mass index[BMI],Lee′s index,and fat index[FI]).Validation studies confirmed that 24-week HFD exposure induced hallmark metabolic derangements and renal pathology:serum fasting blood glucose(FBG),total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),non-esterified fatty acids(NEFA),blood urea nitrogen(BUN),and serum creatinine(SCr)were significantly elevated,whereas high-density lipoprotein cholesterol(HDL-C)levels declined.Oral glucose tolerance tests(OGTT)demonstrated impaired glucose homeostasis.The pathological morphology of the kidney tissues and the ultrastructure of the proximal tubule epithelial cells in the mice both exhibited abnormalities,indicating distinct pathological features in the model animals.Collectively,these data demonstrated that sustained 24-week administration of a 60%HFD in C57BL/6J mice established a robust ORG model that recapitulated both etiopathogenic drivers and histopathological hallmarks of human obesity-related nephropathy,offering a translational platform for therapeutic exploration.

关 键 词：肥胖相关性肾病 高脂饲料 小鼠 动物模型 

分 类 号：R259[医药卫生—中西医结合] R277.5[医药卫生—中医内科学] R575.5[医药卫生—中医学]