卡格列净通过TGF-β/STAT3减轻STZ诱导的糖尿病肾病小鼠肾损伤  

Canagliflozin Alleviates Kidney Damage in STZ-induced Diabetic Nephropathy Mice by TGF-β/STAT3

作　　者：曾维新[1] 云川 李晓燕 李大伟 ZENG Weixin;YUN Chuan;LI Xiaoyan;LI Dawei(Department of Endocrinology,the First Affiliated Hospital of Hainan Medical University,Haikou,570102,China)

机构地区：[1]海南医学院第一附属医院内分泌科,海口市570102

出　　处：《医学分子生物学杂志》2024年第5期432-436,共5页Journal of Medical Molecular Biology

基　　金：海南省卫生健康行业科研项目(No.20A200012)。

摘　　要：目的探讨卡格列净通过TGF-β/STAT3减轻链脲佐菌素(streptozotocin,STZ)诱导的糖尿病肾病小鼠肾损伤潜在机制。方法使用STZ建立糖尿病肾病小鼠模型,分为正常对照组、STZ诱导的糖尿病肾病小鼠组、卡格列净治疗组、TGF-β抑制剂治疗组和STAT3抑制剂治疗组。测量肾重/体重比、尿白蛋白、肾功能参数和血清TGF-β水平,以及肾脏中STAT3的磷酸化水平。结果糖尿病肾病小鼠表现出肾损伤迹象,包括肾重/体重比和尿白蛋白显著增加(P<0.05),而卡格列净治疗后这些指标恢复到正常水平。血清中TGF-β水平在糖尿病肾病小鼠中升高(P<0.05),而卡格列净治疗后恢复至对照水平。糖尿病肾病小鼠肾脏中STAT3的磷酸化水平显著增加(P<0.05),而卡格列净治疗可阻止这种增加,但未影响STAT3总水平。此外,TGF-β表达与STAT3磷酸化呈正相关(P<0.05)。结论卡格列净通过调节TGF-β和STAT3途径减轻糖尿病肾病的肾损伤。Objective To explore the potential mechanism by which canagliflozin alleviates kidney injury in streptozotocin(STZ)-induced diabetic nephropathy mice through TGF-β/STAT3.Methods A diabetic nephropathy mouse model was established using STZ.Mice were divided into 5 groups:control group,STZ-induced diabetic nephropathy mice group,canagliflozintreated group,TGF-βinhibitor-treated group,and STAT3 inhibitor-treated group.Renal weight/body weight ratio,urinary albumin,renal function parameters,serum TGF-βlevel and the phosphorylation level of STAT3 in the kidney tissues were measured.Results Mice with diabetic nephropathy exhibited signs of renal injury,including a significant increase in renal weight/body weight ratio and urinary albumin(P<0.05),whereas these indices returned to normal levels after canagliflozin treatment.The serum TGF-βlevel and phosphorylation level of STAT3 in tissues were elevated in diabetic nephropathy mice(P<0.05),while they returned to similar levels as that in the control after canagliflozin treatment.In addition,the TGF-βexpression level was positively correlated with the STAT3 phosphorylation level(P<0.05).Conclusion Canagliflozin attenuated renal injury in diabetic nephropathy by modulating TGF-βand STAT3 pathways.

关 键 词：卡格列净 TGF-Β STAT3 糖尿病肾病 肾损伤 

分 类 号：R587.2[医药卫生—内分泌] R692[医药卫生—内科学]