紫檀芪延缓糖尿病肾病发展的作用及机制

The role of pterostilbene delaying the development of diabetic nephropathy and its mechanism

目的研究紫檀芪对链脲佐菌素(STZ)诱导的糖尿病肾病(DN)进展的延缓作用及可能机制。方法将C57BL/6J小鼠(n=50)随机分为对照组、模型组、低剂量药物组(20 mg·kg^-1)、中剂量药物组(40 mg·kg^-1)和高剂量药物组(80 mg·kg^-1),每组10只。对照组和模型组灌胃5 g·L^-1羧甲基纤维素钠,高、中、低剂量药物组小鼠灌胃相应剂量的紫檀芪12周。测定24 h蛋白尿,检测血液中血糖、血肌酐和血尿素氮水平,检测肾脏组织中炎症因子白介素-6(IL-6)和单核细胞趋化蛋白-1(MCP-1)的表达,HE染色和PAS染色检测肾脏组织的病理改变情况,Western blot法测定肾脏组织中沉默信息调节因子1(SIRT1)蛋白的表达。结果紫檀芪可延缓STZ诱导的1型DN的进展,降低血肌酐和血尿素氮的水平。紫檀芪对血糖及24 h尿蛋白无影响。紫檀芪可降低肾脏组织中炎症因子IL-6和MCP-1的表达。HE染色和PAS染色发现,紫檀芪能降低糖尿病小鼠肾小球体积和基底膜厚度,还能增加糖尿病小鼠肾脏组织中SIRT1蛋白的表达。结论紫檀芪可延缓1型DN的发展,其机制与其调节SIRT1的表达有关。

Objective To investigate the effect and mechanism of pterostilbene on streptozotocin(STZ)-induced diabetic nephropathy(DN).Methods C57BL/6J mice(n=50)were divided into 5 groups(n=10 per group):control group,model group,pterostilbene low dose group(20 mg·kg^-1),pterostilbene middle dose group(40 mg·kg^-1)and pterostilbene high dose group(80 mg·kg^-1).The mice in the control group and model control group were treated with 5 g·L^-1 CMC-Na,and the mice in the pterostilbene group were intragastrically administered with pterostilbene for 12 weeks.The levels of 24 h proteinuria,blood glucose,creatinine and blood urea nitrogen were detected.The levels of interleukin 6(IL-6)and monocythe chemotactic protein 1(MCP-1)in kidney tissue were determined.The kidney histology was detected by HE and PAS staining.The level of protein expression of silent information regulator 1(SIRT1)was detected by using Western blot method.Results Pterostilbene delayed the progression of STZ-induced DN,and decreased the levels of creatinine and blood urea nitrogen in diabetic mice,compared with model group mice.Pterostilbene had no effect on blood glucose and 24 h proteinuria.Pterostilbene reduced the expression of inflammatory factors IL-6 and MCP-1 in kidney tissues.HE and PAS staining found that pterostilbene reduced glomerular volume and basement membrane thickness in diabetic mice.Pterostilbene was also able to increase the expression of SIRT1 in the kidney tissue of diabetic mice.Conclusion Pterostilbene inhibits the development of STZ-induced DN,and its mechanism is associated with the regulation of SIRT1 expression.