摘要
目的 探讨达格列净对糖尿病肾病(diabeticnephropathy,DN)大鼠的肾脏保护作用及对AMP活化蛋白激酶(AMP-activated protein kinase,AMPK)/哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,m TOR)信号通路表达的影响。方法 SPF级Wistar雄性大鼠40只,随机分为正常组、模型组、低剂量组和高剂量组,每组各10只。成功制备DN模型后,正常组大鼠给予普通饲料+生理盐水灌胃;模型组大鼠给予高糖高脂饲料+生理盐水灌胃;低剂量组大鼠给予高糖高脂饲料+达格列净1mg/(kg·d)灌胃;高剂量组大鼠给予高糖高脂饲料+达格列净10mg/(kg·d)灌胃。各组大鼠连续干预12周。比较各组大鼠的肾功能指标、肾脏病理组织变化、p-AMPK和p-mTOR蛋白表达、Ⅰ型胶原(collagen typeⅠ,COLⅠ)、Ⅳ型胶原(collagen typeⅣ,COLⅣ)、纤维连接蛋白(fibronectin,FN)水平。结果 模型组、低剂量组和高剂量组大鼠的血尿素氮(blood urea nitrogen,BUN)、血肌酐(serum creatinine,SCr)、24h尿蛋白定量、p-mTOR蛋白表达、COLⅠ、COLⅣ和FN水平均显著高于正常组,p-AMPK蛋白表达显著低于正常组(P<0.05);低剂量组和高剂量组大鼠的BUN、SCr、24h尿蛋白定量、p-mTOR蛋白表达、COLⅠ、COLⅣ和FN水平均显著低于模型组,p-AMPK蛋白表达显著高于模型组(P<0.05);高剂量组大鼠的BUN、SCr、24h尿蛋白定量、p-mTOR蛋白表达、COLⅠ、COLⅣ和FN水平均显著低于低剂量组,p-AMPK蛋白表达显著高于低剂量组(P<0.05)。结论 达格列净对DN大鼠具有良好的肾脏保护作用,其机制可能与调节AMPK/mTOR信号通路表达有关。
Objective To investigate the protective effect of dapagliflozin on kidney and the expression of AMP-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)signaling pathway in diabetic nephropathy(DN)rats.Methods A total of 40 SPF Wistar male rats were randomly divided into normal group,model group,low-dose group and high-dose group,with 10 rats in each group.After the DN model was successfully prepared,the rats in normal group were given normal diet+normal saline by gavage,the rats in model group was given high sugar and high fat feed+normal saline by gavage,the rats in low-dose group was given high sugar and high fat feed+1mg/(kg·d)of dapagliflozin by gavage,the rats in high-dose group was given high sugar and high fat feed+10mg/(kg·d)of dapagliflozin by gavage.Rats in each group were continuously gavaged for 12 weeks.Renal function indexes,renal pathological changes,p-AMPK and p-mTOR protein expression,collagen typeⅠ(COLⅠ),collagen typeⅣ(COLⅣ)and fibronectin(FN)of all groups were compared.Results Blood urea nitrogen(BUN),serum creatinine(SCr),24h urinary protein quantity,p-mTOR protein expression,COLⅠ,COLⅣand FN levels of rats in model group,low-dose group and high-dose group were significantly higher than those in normal group,and p-AMPK protein expression was significantly lower than that of normal group(P<0.05).BUN,SCr,24h urinary protein quantity,p-mTOR protein expression,COLⅠ,COLⅣand FN levels of rats in low-dose group and high-dose group were significantly lower than those in model group,while p-AMPK protein expression was significantly higher than that in model group(P<0.05).BUN,SCr,24h urinary protein quantity,p-mTOR protein expression,COLⅠ,COLⅣand FN levels in high-dose group were significantly lower than those in low-dose group,and p-AMPK protein expression was significantly higher than that in low-dose group(P<0.05).Conclusion Dapagliflozin has a good kidney protection effect on DN rats,and its mechanism may be related to the regulation of AMPK/mTOR signaling pathway
作者
叶玉燕
王鹏
方霞
杨静
YE Yuyan;WANG Peng;FANG Xia;YANG Jing(Department of Nephrology,Jinhua People’s Hospital,Jinhua 321000,Zhejiang,China;Department of Pharmacy,Jinhua People’s Hospital,Jinhua 321000,Zhejiang,China)
出处
《中国现代医生》
2024年第10期60-63,71,共5页
China Modern Doctor
基金
浙江省公益类金华市科学技术研究计划项目(2021-4-067)。
