摘要
目的探究达格列净治疗早期糖尿病肾病(DKD)大鼠的作用机制。方法选择适应性饲养1周的32只大鼠为研究对象。随机选取8只为对照组,其余注射链脲佐菌素(STZ)并给予高脂高糖饲料喂养制备DKD模型,将造模后的大鼠均分为模型组、二甲双胍组和达格列净组,分别用生理盐水、二甲双胍和达格列净进行灌胃处理。比较各组的血糖、肾功能指标、肾脏纤维化指标及Notch信号通路相关蛋白表达水平。结果灌胃开始第1天及第3、6、9周,模型组的空腹血糖(FBG)、血肌酐(Scr)、24 h尿微量白蛋白、尿素氮(Ure)、转化生长因子β1(TGF-β1)、胶原蛋白Ⅰ(Col-Ⅰ)水平均明显高于对照组(P<0.05);灌胃开始第1天及第3、6、9周,二甲双胍组和达格列净组的FBG、Scr、24h尿微量白蛋白、Ure、TGF-β1及Col-Ⅰ水平明显低于模型组,且达格列净组显著低于二甲双胍组(P<0.05)。灌胃处理9周后,达格列净组Notch信号通路蛋白Notch1、NICD1、Jagged1和Hes1表达水平明显低于模型组和二甲双胍组(P<0.05)。结论达格列净可通过抑制Notch信号通路过度激活,抑制相关蛋白表达和肾脏纤维化进程,发挥保护肾脏和治疗早期DKD的作用。
Objective To investigate the action mechanism of dapagliflozin in the treatment of early diabetic kidney disease(DKD)in rats.Methods Thirty two rats were selected as the study objects after one week of adaptive feeding.Eight rats were randomly selected as control group,and the rest were injected with streptozotocin(STZ)and fed with high-fat and high-sugar diet to prepare DKD model.The successful model rats were divided into model group,metformin group and dapagliflozin group,and were gavaged with normal saline,metformin and dapagliflozin respectively.Blood glucose,renal function indexes,renal fibrosis indexes and Notch signal pathway related proteins expression levels were compared among the groups.Results On the first day and the third,sixth and ninth weeks after intragastric administration,the levels of fasting blood glucose(FBG),serum creatinine(Scr),24 h urinary microalbumin,urea nitrogen(Ure),transforming growth factorβ1(TGF-β1)and collagenⅠ(Col-Ⅰ)in the model group were significantly higher than those in the control group(P<0.05);on the first day and the third,sixth and ninth weeks after intragastric administration,the levels of FBG,Scr,24 h urinary microalbumin,Ure,TGF-β1and Col-Ⅰin the metformin group and the dapagliflozin group were significantly lower than those in the model group,and those in the dapagliflozin group were significantly lower than the metformin group(P<0.05).After 9 weeks of intragastric administration,the expression levels of Notch signaling pathway proteins Notch1,NICD1,Jagged1and Hes1 in the dapagliflozin group were significantly lower than those in the model group and the metformin group(P<0.05).Conclusion Dapagliflozin can play a role in protecting the kidney and treating early DKD by inhibiting the over-activation of Notch signaling pathway and suppressing the expression of related proteins and the process of renal fibrosis.
作者
张一婷
雷洁
李琳
ZHANG Yiting;LEI Jie;LI Lin(Nephrology Department,Xi'an Central Hospital,Xi'an 710003,China)
出处
《临床医学研究与实践》
2022年第19期15-18,共4页
Clinical Research and Practice
基金
陕西省自然科学基础研究计划项目(No.2021JQ-931)。
