Xu Xiaohui, Zheng Ni, Chen Zhaoni, Huang Wansu, Liang Tao, Kuang Hai
Pharmaceutical College, Guangxi Medical University, Nanning, Guangxi 530021, PR China.
Shenzhen University, Shenzhen, Guangdong 518060, PR China.
Gene. 2016 Oct 15;591(2):411-6. doi: 10.1016/j.gene.2016.06.032. Epub 2016 Jun 16.
In this study, we evaluated the effect of puerarin (PR) on diabetic nephropathy (DN) in streptozotocin (STZ)-induced diabetic mice. The fasting blood glucose (FBG), blood urea nitrogen (BUN) and serum creatinine (Scr), as well as 24-hour urine protein levels were effectively ameliorated in DN mice treated with PR (20, 40, 80mg/kg/day). Furthermore, PR treatment markedly resulted in down-regulation of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and reactive oxygen species (ROS) in kidney. Interestingly, the activities of manganese superoxide dismutase (MnSOD) and catalase (CAT) were increased by PR. An improvement in kidney tissue damage could be observed after PR administration. Further ultrastructural investigation revealed a dramatically ameliorative effect of PR on mitochondrial damage. Meanwhile, the silent information regulator 1 (SIRT1), forkhead box protein O1 (FOXO1) and alpha subunit of peroxisome proliferators-activated receptor-gamma coactivator-1 (PGC-1α) expressions were significantly up-regulated at protein level by PR administration in renal cortex. However, the protein expression of nuclear-factor kappa B (NF-κB) was down-regulated in PR groups. Our present study demonstrates the hypoglycemic and renal protective effects of PR in DN mice, which support its anti-diabetic property. PR exerts its renal protection effect probably via the mechanism of attenuating SIRT1/FOXO1 pathway for renal protection.
在本研究中，我们评估了葛根素（PR）对链脲佐菌素（STZ）诱导的糖尿病小鼠糖尿病肾病（DN）的影响。用PR（20、40、80mg/kg/天）治疗的DN小鼠，其空腹血糖（FBG）、血尿素氮（BUN）、血清肌酐（Scr）以及24小时尿蛋白水平均得到有效改善。此外，PR治疗显著导致肾脏中白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和活性氧（ROS）水平下调。有趣的是，PR可提高锰超氧化物歧化酶（MnSOD）和过氧化氢酶（CAT）的活性。给予PR后可观察到肾组织损伤有所改善。进一步的超微结构研究显示，PR对线粒体损伤具有显著的改善作用。同时，在肾皮质中，PR给药可使沉默信息调节因子1（SIRT1）、叉头框蛋白O1（FOXO1）和过氧化物酶体增殖物激活受体γ共激活因子-1α（PGC-1α）的蛋白表达显著上调。然而，PR组中核因子κB（NF-κB）的蛋白表达下调。我们目前的研究证明了PR对DN小鼠具有降血糖和肾脏保护作用，这支持了其抗糖尿病特性。PR可能通过减弱SIRT1/FOXO1通路来发挥肾脏保护作用。
