达格列净抑制2型糖尿病小鼠心血管及肾脏并发症的研究

Dapagliflozin Ameliorates Cardiovascular and Renal Injury in Type 2 Diabetic Mice

目的:探讨达格列净对2型糖尿病小鼠心、肾的保护作用。方法:选取24只6周龄的雄性2型糖尿病模型(C57BLKS/J-leprdb/leprdb,db/db)小鼠,随机等分成达格列净投药组和对照组,另选取同周龄雄性非糖尿病的(C57BLKS/J-leprdb/+,db/m)小鼠12只作为正常组。检测小鼠血糖后,从第7周开始对投药组小鼠进行为期10周的达格列净用药,其余小鼠给予同等计量生理盐水,期间定期监测血糖、血压、尿糖以及各项代谢相关指标。投药结束后分离心脏及肾脏组织,组织切片进行染色观察。结果:与对照组相比,投药组达格列净用药后第1周血糖值显著降低(P<0.01),用药9周后糖耐量测试结果显示血糖值几乎接近正常小鼠组水平,但各组间血压值无明显差异,心肌间质纤维化、炎性细胞浸润、氧化应激水平明显下降,同时肾小球硬化、炎性细胞浸润和氧化应激程度明显得到改善。结论:达格列净用药不仅能显著降低2型糖尿病模型小鼠血糖,还能有效抑制糖尿病引起的心血管及肾损害。

Objective:To determine whether dapagliflozin can ameliorate cardiovascular and renal complications in type 2 diabetic mice.Methods:24 six-weeks-old male db/db(C57 BLKS/J-leprdb/leprdb,db/db)mice were chosen and randomly divided into dapagliflozin treatment group and control group(n=12 each),and nondiabetic db/m(C57 BLKS/J-lepr db/+,db/m)mice at the same ages were involved as the normal group(n=12).A 10-week dapagliflozin administration began at 7 weeks of age after determination of the blood glucose of the mice and the other two groups were given with the same dose of normal saline;and blood glucose,blood pressure,urine glucose and metabolic related indicators were measured during the treatment.Heart and renal tissues were separated and sections were stained after administration.Results:Dapagliflozin administration effectively controlled blood glucose in db/db mice by one week of the treatment and kept blood glucose at an ideal level(P<0.01),and no difference was observed in with db/m mice in blood glucose throughout 9 weeks dapagliflozin administration in OGTT test.However,blood pressure was no comparable between control and dapagliflozin administration group.Dapagliflozin administration could significantly ameliorated cardiac interstitial fibrosis and glomerular injury,and also improved macrophage infiltration and oxidative stress in cardiac and renal tissue in db/db mice.Conclusions:Dapagliflozin in glycemic control can ameliorate cardiovascular complication and renal injury.