Liang Jin, Tian Shoufu, Han Junxia, Xiong Peihua
Department of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Soochow University , Suzhou , China and.
Ren Fail. 2014 Mar;36(2):285-91. doi: 10.3109/0886022X.2013.844644. Epub 2013 Oct 24.
Renal fibrosis is a common outcome of chronic kidney disease. This study was designed to examine the protective effects of resveratrol (RSV) against renal fibrosis induced by unilateral ureteral obstruction (UUO). We also attempted to elucidate the potential mechanism involved.
Mice were randomly divided into three groups: sham-operated, UUO, and UUO/RSV (20 mg·kg(-1)·day(-1)). Histological changes were examined using periodic acid-Schiff and Masson's trichrome staining after 14 days. Superoxide dismutase (SOD), malondialdehyde (MDA), and 8-OHdG levels were determined using a commercially available kit. ICAM-1, TNF-α, and TGF-β levels were measured using real-time PCR. Fibronectin levels were measured by western blot, and the Smad3 acetylation and Sirt1 were examined by immunoprecipitation and western blot.
Our study showed that RSV treatment significantly attenuated renal injury including extracellular matrix deposition and tubulointerstitium damage. Renal cortical mRNA levels of ICAM-1, TNF-α, and TGF-β, protein expression of fibronectin and Smad3 acetylation were significantly upregulated in the UUO group. However, treatment with RSV significantly decreased the expression of these proteins. Furthermore, RSV also decreased the levels of reactive oxygen species (ROS) including MDA and 8-OHdG, and increased the level of SOD, which protects cells against ROS damage.
Our findings suggest that RSV treatment inhibits oxidative stress, Smad3 acetylation, and renal interstitial fibrosis. Therefore, RSV may have potential as a therapeutic target for the treatment of chronic kidney disease.
肾纤维化是慢性肾脏病的常见结局。本研究旨在探讨白藜芦醇（RSV）对单侧输尿管梗阻（UUO）诱导的肾纤维化的保护作用。我们还试图阐明其中潜在的机制。
将小鼠随机分为三组：假手术组、UUO组和UUO/RSV组（20mg·kg⁻¹·天⁻¹）。14天后，采用高碘酸-希夫染色和Masson三色染色检查组织学变化。使用市售试剂盒测定超氧化物歧化酶（SOD）、丙二醛（MDA）和8-羟基脱氧鸟苷（8-OHdG）水平。采用实时聚合酶链反应测定细胞间黏附分子-1（ICAM-1）、肿瘤坏死因子-α（TNF-α）和转化生长因子-β（TGF-β）水平。通过蛋白质印迹法测定纤连蛋白水平，并通过免疫沉淀和蛋白质印迹法检测Smad3乙酰化和沉默信息调节因子1（Sirt1）。
我们的研究表明，RSV治疗显著减轻了肾损伤，包括细胞外基质沉积和肾小管间质损伤。UUO组肾皮质ICAM-1、TNF-α和TGF-β的mRNA水平、纤连蛋白的蛋白表达和Smad3乙酰化均显著上调。然而，RSV治疗显著降低了这些蛋白的表达。此外，RSV还降低了包括MDA和8-OHdG在内的活性氧（ROS）水平，并提高了SOD水平，SOD可保护细胞免受ROS损伤。
我们的研究结果表明，RSV治疗可抑制氧化应激、Smad3乙酰化和肾间质纤维化。因此，RSV可能具有作为慢性肾脏病治疗靶点的潜力。
