摘要
目的探讨SGLT2抑制剂达格列净(SGLT2i)对糖尿病肾病(diabetic nephropathy,DN)小鼠的作用,为临床治疗DN提供实验室依据.方法选用10周龄雄性db/db小鼠(n=21 DN模型)和10周龄雄性wt小鼠(n=20野生模型),随机分wt组(未治疗野生组)、wt+SGLT2i组(治疗野生组)、db/db组(未治疗DN组)、db/db+SGLT2i组(治疗DN组).连续饲养12周,确定制成DN模型后,给予SGLT2i达格列净灌胃,8周后取材,行生化检查、病理、免疫组化、蛋白印迹及TUNEL染色.结果和wt组比较,db/db小鼠DN组血糖、肾质量/体质量比、血肌酐、24 h尿蛋白及尿微量白蛋白与肌酐的比值(UACR)均明显升高,而体质量明显降低(均P<0.05).与db/db组比较,db/db+SGLT2i达格列净组UACR、24 h尿蛋白、血肌酐及血糖水平明显降低,体质量也有所减轻(均P<0.05),但肾质量/体质量比值无明显变化.组织病理学结果显示:与wt组比较,db/db组肾小球鲍曼间隙缩小,肾小球基底膜增厚,系膜基质扩张,系膜细胞增生.与db/db组比较,db/db+SGLT2i达格列净组上述病理改变均减轻.透射电镜观察肾脏的超微结构结果显示:与wt组比较,db/db组肾小球基底膜增厚,膜滤过层结构不清,足细胞足突紊乱,间隙增宽,系膜基质增多.与db/db组比较,db/db+SGLT2i组的上述症状明显减轻,表明SGLT2i达格列净可以减轻db/db小鼠的肾脏损伤.与wt组比较,db/db DN组小鼠肾小管上皮细胞凋亡明显升高,与db/db组比较,db/db+SGLT2i达格列净组细胞凋亡明显降低(P<0.05).结论SGLT2i达格列净可减轻db/db小鼠的肾损伤;SGLT2i达格列净可减少db/db DN小鼠模型的细胞凋亡及ERS途径相关蛋白Caspase12蛋白的表达;SGLT2i达格列净对DN小鼠有保护作用,其可能的机制与改善ERS细胞凋亡途径有关.
Objective To investigate the effect of SGLT2i inhibitor Dapagliflizin on DN mice and further study its mechanism,so as to provide a strong laboratory basis for the clinical treatment of DN.Method 10-week-old male db/db mice(n=21 DN model)and 10-week-old male wt mice(n=20 wild model)were used and randomly divided into wt group(untreated wild group),wt+SGLT2i group(treated wild group),db/db group(untreated DN group),db/db+SGLT2I group(treated DN group).DN model was established after 12 weeks of continuous feeding,and SGLTi Dapagliflizin was given by gavage,and samples were collected 8 weeks later.Biochemistry,pathology,immunohistochemistry,Western blot and TUNEL staining were performed.Results Compared with wt group,blood glucose,kidney weight/body weight ratio,serum creatinine,24-hour urinary protein and UACR in db/db DN group were significantly higher,while body weight was significantly lower(P<0.05).Compared with db/db group,the levels of UACR,24-hour urinary protein,serum creatinine and blood glucose in db/db+SGLT2i group were significantly lower,and their body weight was also reduced(P<0.05),but the ratio of kidney weight to body weight had no significant change.The histopathological results showed that compared with wt group,glomerular Bowman space decreased,glomerular basement membrane thickened,Mesangial matrix dilated and Mesangial cells proliferated in db/db group.Compared with db/db group,the above pathological changes were alleviated in db/db+SGLT2i group.The ultrastructure of kidney was observed by transmission electron microscope.Compared with wt group,the glomerular basement membrane of db/db group was thicker,the structure of membrane filtration layer was unclear,the foot process of podocyte was disordered,the space was widened and the Mesangial matrix was increased.Compared with the db/db group,the above findings in the db/db+SGLT2i group were significantly alleviated,indicating that SGLT2i Dapagliflizin can alleviate the renal injury in db/db mice.Compared with wt group,the apoptosis of renal tubu
作者
曹雨琛
李成强
刘鉴颖
宋葳
孙昕昳
CAO Yuchen;LI Chengqiang;LIU Jianying;SONG Wei;SUN Xinyi(Affiliated Hospital of Beihua University,Jilin 132011,China)
出处
《北华大学学报（自然科学版）》
CAS
2022年第1期64-69,共6页
Journal of Beihua University（Natural Science）
基金
吉林省科技发展计划项目(20200201354JC)
吉林省卫生与健康技术创新项目(2018J80,2018J086)
吉林市医疗卫生指导性计划项目(201830579).
