摘要
目的:探讨知柏地黄汤对糖尿病大鼠的肾脏保护作用是否与钠-葡萄糖共转运体2(SGLT2)抑制剂相似。方法:采用高脂饮食和低剂量链脲佐菌素(STZ)建立糖尿病大鼠模型。将空腹血糖>11.1 mmol/L的大鼠随机分为知柏地黄汤组、达格列净组、糖尿病组。所有大鼠每周称重1次。在第45天和第90天进行尾静脉采血,测定血清葡萄糖(S-Glu)、糖化血清蛋白(GSP)、血清尿素(Urea)、血清肌酐(Scr)、血清Na^(+)(S-Na^(+))。在最后1周收集所有大鼠的24 h尿液,测定尿葡萄糖(U-Glu)、尿微量白蛋白(U-ALB)、尿钠(U-Na^(+))、尿肌酐(Ucr)。治疗90 d后处死所有大鼠,取肾脏进行HE染色、电镜观察及SGLT2、NOD样受体蛋白3(Nlrp3)和白介素-1β(IL-1β)蛋白检测。结果:知柏地黄汤和达格列净恢复了糖尿病引起的体质量减轻(P<0.05),与糖尿病组比较,知柏地黄汤组和达格列净组肾质量、肾质量/体质量、S-Glu、GSP、Urea、Scr、U-ALB及尿蛋白肌酐比(UACR)水平均明显降低(P<0.05),U-Glu均明显升高(P<0.05),S-Na^(+)及U-Na^(+)水平均无明显差异(P>0.05)。与糖尿病组相比,知柏地黄汤组和达格列净组肾脏SGLT2、Nlrp3和IL-1β蛋白表达水平均明显降低(P<0.05)。HE染色及电镜结果显示,与糖尿病组相比,知柏地黄汤组及达格列净组肾脏结构病变明显减轻、足突融合减少。结论:知柏地黄汤能有效减轻糖尿病大鼠肾功能损伤,减少肾脏SGLT2的表达,减少炎症介质Nlrp3/IL-1β的表达,提示其肾脏保护作用与SGLT2抑制剂相似。
Object:To investigate whether the renal protective effect of Zhibai Dihuang Decoction on diabetic rats is similar to that of sodium glucose co-transporter 2(SGLT2)inhibitor.Methods:A diabetic rat model was established by high-fat diet and low dose of streptozotocin(STZ).Rats with fasting blood glucose levels>11.1 mmol/L were randomly divided into 3 groups:Zhibai Dihuang Decoction(ZBDHD)group,dapagliflozin(Dapa)group and diabetes group.All rats were weighed once a week.Caudal vein blood collection were conducted on the 45th and 90th day to measure serum glucose(S-Glu),glycosylation serum protein(GSP),serum urea(S-Urea),serum creatinine(Scr)and serum sodium(S-Na^(+)).24 h urine of all rats were collected in the last week to measure urine glucose(U-Glu),urine microalbumin(U-ALB),urine sodium(U-Na^(+))and urine creatinine(Ucr).All rats were executed after 90th day of treatment accordingly,and their kidneys were taken for HE staining,electron microscopy and protein detection of SGLT2,Nlrp3 and IL-1β.Result:Zhibai Dihuang Decoction and dapagliflozin recovered the weight loss caused by diabetes(P<0.05).Compared with diabetes group,kidney weight,the ratio of kidney weight to body weight,S-Glu,GSP,Urea,Scr,U-ALB and urinary protein creatinine ratio(UACR)levels in the ZBDHD group and the Dapa group were significantly lower(P<0.05),U-Glu increased significantly(P<0.05),and there was no significant difference in S-Na^(+)and U-Na^(+)level(P<0.05).Compared with the diabetes group,the protein expression levels of SGLT2,Nlrp3 and IL-1βin the kidneys of the ZBDHD group and Dapa group were significantly lower(P<0.05).The results of HE staining and electron microscopy showed that compared with the diabetic group,the kidney structural lesions in ZBDHD and Dapa group were significantly alleviated,and the fusion of foot processes of podocytes was reduced.Conclusion:Zhibai Dihuang Decoction can effectively alleviated the renal function impairment,relieved the expression of SGLT2 in renal,and relieved the expression of Nlrp3/IL-1 in t
作者
唐明娟
熊哲学
熊锐
李凝旭
TANG Ming-juan;XIONG Zhe-xue;XIONG Rui;LI Ning-xu(Liyuan Hospital of Tongji Medical College of Huazhong University of Science and Technology,Wuhan Hubei 430077,China)
出处
《中医药导报》
2022年第1期19-24,共6页
Guiding Journal of Traditional Chinese Medicine and Pharmacy
