Wu Chia-Chao, Huang Yen-Sung, Chen Jin-Shuen, Huang Ching-Feng, Su Sui-Lung, Lu Kuo-Cheng, Lin Yuh-Feng, Chu Pauling, Lin Shih-Hua, Sytwu Huey-Kang
Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan.
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
PLoS One. 2015 May 8;10(5):e0125726. doi: 10.1371/journal.pone.0125726. eCollection 2015.
Idiopathic membranous nephropathy (MN) is an autoimmune-mediated glomerulonephritis and a common cause of nephrotic syndrome in adults. There are limited available treatments for MN. We assessed the efficacy of resveratrol (RSV) therapy for treatment of MN in a murine model of this disease.
Murine MN was experimentally induced by daily subcutaneous administration of cationic bovine serum albumin, with phosphate-buffered saline used in control mice. MN mice were untreated or given RSV. Disease severity and pathogenesis was assessed by determination of metabolic and histopathology profiles, lymphocyte subsets, immunoglobulin production, oxidative stress, apoptosis, and production of heme oxygenase-1 (HO1).
MN mice given RSV had significantly reduced proteinuria and a marked amelioration of glomerular lesions. RSV also significantly attenuated immunofluorescent staining of C3, although there were no changes of serum immunoglobulin levels or immunocomplex deposition in the kidneys. RSV treatment of MN mice also reduced the production of reactive oxygen species (ROS), reduced cell apoptosis, and upregulated heme oxygenase 1 (HO1). Inhibition of HO1 with tin protoporphyrin IX partially reversed the renoprotective effects of RSV. The HO1 induced by RSV maybe via Nrf2 signaling.
Our results show that RSV increased the expression of HO1 and ameliorated the effects of membranous nephropathy in a mouse model due to its anti-complement, anti-oxidative, and anti-apoptotic effects. RSV appears to have potential as a treatment for MN.
特发性膜性肾病（MN）是一种自身免疫介导的肾小球肾炎，是成人肾病综合征的常见病因。MN的可用治疗方法有限。我们评估了白藜芦醇（RSV）治疗MN小鼠模型的疗效。
通过每日皮下注射阳离子牛血清白蛋白实验性诱导小鼠MN，对照小鼠注射磷酸盐缓冲盐水。MN小鼠不治疗或给予RSV。通过测定代谢和组织病理学特征、淋巴细胞亚群、免疫球蛋白产生、氧化应激、细胞凋亡和血红素加氧酶-1（HO1）的产生来评估疾病严重程度和发病机制。
给予RSV的MN小鼠蛋白尿显著减少，肾小球病变明显改善。RSV还显著减弱了C3的免疫荧光染色，尽管血清免疫球蛋白水平或肾脏中的免疫复合物沉积没有变化。RSV治疗MN小鼠还减少了活性氧（ROS）的产生，减少了细胞凋亡，并上调了血红素加氧酶1（HO1）。用锡原卟啉IX抑制HO1部分逆转了RSV的肾脏保护作用。RSV诱导的HO1可能通过Nrf2信号传导。
我们的结果表明，RSV通过其抗补体、抗氧化和抗凋亡作用增加了HO1的表达并改善了小鼠模型中膜性肾病的影响。RSV似乎有作为MN治疗方法的潜力。
