恩格列净通过抑制细胞焦亡改善糖尿病小鼠肾脏损伤

目的研究恩格列净(empagliflozin)对db/db小鼠肾脏损伤的保护作用及其潜在作用机制。方法db/db小鼠随机分为糖尿病肾病组(db/db组)和恩格列净治疗组(Empa组,恩格列净10 mg·kg-1·d-1灌胃),C57BL/6J小鼠作为正常对照组。干预3个月,检测血清生化、炎症因子等指标;病理染色观察肾脏病理学改变;检测细胞焦亡相关分子NLRP3、Cleaved Caspase-1、GSDMD的蛋白表达水平。结果与db/db组相比,Empa组空腹血糖、HbA1C、血脂、血清IL-1β、IL-18及ACR明显降低(均P<0.05),病理染色显示Empa组肾小球固缩、肾间质纤维化明显改善,Empa组肾脏组织NLRP3、Cleaved Caspase-1、GSDMD蛋白表达下调(P<0.05)。结论恩格列净可能通过抑制NLRP3/Caspase-1/GSDMD细胞焦亡信号通路而改善糖尿病小鼠肾脏损伤。

Effect of englitazine on improving renal injury in diabetic mice by inhibiting pyroptosis

Objective To investigate the effect of empagliflozin on diabetic kidney disease in db/db mice and the potential mechanisms.Methods db/db mice were randomly divided into db/db group and Empa group.C57BL/6J mice were used as normal control group.We measured the level of serum biochemistry and inflammatory cytokines.Pathological changes of kidney were observed by pathological staining.The protein expression levels of NLRP3,cleaved caspase-1 and GSDMD were detected.Results Compared with db/db group,the level of fasting blood glucose,blood lipids,serum biochemistry,and urinary protein-to-creatinine ratio in Empa group were significantly decreased(P<0.05).HE staining and Masson staining showed that empagliflozin could significantly improve glomerular pyknosis and renal interstitial fibrosis in db/db mice.Meanwhile,the expressions of NLRP3,cleaved caspase-1,and GSDMD protein were down-regulated(P<0.05).Conclusion Empagliflozin improves kidney damage in diabetic model mice,and the possible mechanism is to inhibit the cell pyroptosis signal pathway of NLRP3/caspase-1/GSDMD.