白藜芦醇及SRT1720对2型糖尿病大鼠肾小球足细胞裂孔隔膜分子表达的影响

Effects of Resveratrol and SRT1720 on Expression of Podocyte Slit Diaphragm Elements in Diabetic Nephropathy Rats

关键词:  糖尿病肾病  白藜芦醇  SRT1720  Nephrin  Podocin

Key words:  diabetic nephropathy  resveratrol  SRT1720  Nephrin  Podocin

摘要:

目的 研究白藜芦醇和SIRT1激活剂SRT1720对糖尿病大鼠肾功能以及足细胞损伤的干预作用，探讨SIRT1活化改善肾损害的作用和机制。方法 采用高脂饮食联合单侧肾切除和链脲佐菌素诱导方法建立2型糖尿病大鼠模型，用白藜芦醇和SRT1720等进行干预治疗。留取血清和肾脏，分析肾质量及肾质量/体质量，检测空腹血糖、血肌酐、尿素氮等，采用免疫组化、逆转录-实时荧光定量PCR技术检测肾皮质中足细胞裂孔隔膜分子Nephrin和Podocin等蛋白原位表达和基因表达水平。结果 与正常组相比，模型组大鼠单侧肾质量及肾质量/体质量比显著增高（P<0.05），空腹血糖、血肌酐和尿素氮均显著增高（P<0.05），肾皮质中Nephrin和Podocin蛋白表达和基因表达丰度显著降低（P<0.05）。白藜芦醇和SRT1720治疗组各项检测指标均较模型组有所改善，白藜芦醇组肾质量/体质量指数、空腹血糖、Nephrin和Podocin蛋白表达和Nephrin基因表达与模型组有统计学差异（P<0.05），SRT1720组空腹血糖、血肌酐、尿素氮、Nephrin和Podocin表达等与模型组均有统计学差异（P<0.05）。结论 白藜芦醇、SRT1720等SIRT1激活剂可显著改善糖尿病大鼠肾功能和足细胞损伤，在糖尿病肾病的防治方面具有重要价值和应用前途。

Abstract:

OBJECTIVE To observe the effects of resveratrol and SIRT1 activator SRT1720 on renal function and podocyte injury in diabetic rats, and to explore the possible mechanism of silent information regulator 2 related enzyme 1(SIRT1) activation to improve renal damage.METHODS Type 2 diabetic rat model was established by giving fat-enriched diets combined with unilateral nephrectomy and streptozotocin (STZ) intraperitoneal injection. Diabetic rats of the intervention group were treated with SRT1720 and resveratrol. Rats were sacrificed, kidneys and serum were collected to test renal function. Renal weight and renal weight/body weight were measured, fasting blood-glucose, serum creatinine, and urea nitrogen were detected by biochemical technique. The expression levels of podocyte slit diaphragm elements such as Nephrin and Podocin were detected by immunohistochemistry and reverse transcription real-time fluorescent quantitative PCR. RESULTS Compared with normal group, the unilateral kidney weight, ratio of kidney weight to body weight, fasting blood glucose, serum creatinine and urea nitrogen in the model rats increased significantly(P<0.05), while the protein and genetic expression of Nephrin and Podocin in renal cortex were decreased(P<0.05). Each detection index in resveratrol group or SRT1720 group was improved compared with model group. In specific, the ratio of kidney weight/body, fasting blood glucose, protein expression of Nephrin and Podocin, and gene expression of Nephrin were showed statistically significant difference between resveratrol group and model group(P<0.05). Besides, the fasting blood glucose, serum creatinine, and urea nitrogen and molecule expression of Nephrin and Podocin in the SRT1720 group were significantly different from those in the model group(P<0.05). CONCLUSION The SIRT1 activators including resveratrol and SRT1720, can significantly improve renal function damage and podocyte injury in diabetic nephropathy rats, which have important value and application prospect in the prevention and treatment of diabetic nepropathy.