Yoon Jung Joo, Lee Yun Jung, Lee So Min, Kang Dae Gill, Lee Ho Sub
Professional Graduate School of Oriental Medicine and College of Oriental Medicine, Wonkwang University, Shinyong-dong, Iksan, Jeonbuk, 570-749, Republic of Korea.
Hanbang Body-fluid Research Center, Wonkwang University, Shinyong-dong, Iksan, Jeonbuk, 570-749, Republic of Korea.
BMC Complement Altern Med. 2015 Feb 22;15:30. doi: 10.1186/s12906-015-0542-6.
The pathological change of kidney in diabetic nephropathy is represented hypertrophy, inflammation, and renal fibrosis. Oryeongsan, traditional oriental herbal formula, is widely used for the treatment of nephrosis, dropsy, and uremia. This study was examined whether Oryeongsan attenuate high-glucose (HG)-promoted rat mesangial cell fibrosis and matrix accumulation, major features of diabetic glomerulosclerosis.
Oryeongsan was mixed traditional herbal medicine, Alisma orientale Juz, Polyporus umbellatus Fries, Atractylodes macrocephala Koidez, Poria cocos Wolf and Cinnamomum Cassia Presl (5:3:3:1). Renoprotective role in diabetic nephropathy of Oryeongsan was evaluated by [(3)H]-thymidine incorporation, Western blot, RT-qPCR and immunofluorescence microscopy assay.
Rat mesangial cell proliferation induced by HG was significantly accelerated, which was inhibited by Oryeongsan in a dose dependent manner. HG enhanced expression of fibrosis biomarkers such as collagen IV and connective tissue growth factor (CTGF), which was markedly attenuated by Oryeongsan. Oryeongsan increased HG-inhibited membrane type-1 matrix metalloproteinase expression (MT1-MMP) and MMP-2 promotor activity, whereas suppressed HG-induced tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) expression. Moreover, Oryeongsan promoted extracellular matrix degradation through disturbing transforming growth factor β (TGF-β)-Smad signaling. This study further revealed that Oryeongsan ameliorated HG-induced mesangial inflammation accompanying induction of intracellular cell adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1). Moreover, pretreatment of Oryeongsan inhibited NF-κB translocation in HG-exposed mesangial cell.
These results demonstrate that Oryeongsan has protective effect against renal proliferation, fibrosis, and inflammation. Therefore Oryeongsan may be specific therapies targeting renal dysfunction leading to diabetic nephropathy.
糖尿病肾病的肾脏病理变化表现为肥大、炎症和肾纤维化。五苓散是一种传统的东方草药配方，广泛用于治疗肾病、水肿和尿毒症。本研究旨在探讨五苓散是否能减轻高糖（HG）促进的大鼠系膜细胞纤维化和基质积聚，这是糖尿病肾小球硬化的主要特征。
五苓散是由泽泻、茯苓、白术、猪苓和肉桂（5:3:3:1）混合而成的传统草药。通过[³H] - 胸腺嘧啶核苷掺入、蛋白质免疫印迹法、实时定量聚合酶链反应和免疫荧光显微镜分析评估五苓散在糖尿病肾病中的肾脏保护作用。
HG诱导的大鼠系膜细胞增殖显著加速，而五苓散以剂量依赖性方式抑制了这种增殖。HG增强了纤维化生物标志物如IV型胶原和结缔组织生长因子（CTGF）的表达，而五苓散显著减弱了这种增强作用。五苓散增加了HG抑制的膜型1基质金属蛋白酶表达（MT1 - MMP）和MMP - 2启动子活性，同时抑制了HG诱导的基质金属蛋白酶组织抑制剂 - 2（TIMP - 2）表达。此外，五苓散通过干扰转化生长因子β（TGF - β） - Smad信号通路促进细胞外基质降解。本研究进一步表明，五苓散改善了HG诱导的系膜炎症，同时诱导了细胞间黏附分子 - 1（ICAM - 1）和单核细胞趋化蛋白 - 1（MCP - 1）。此外，五苓散预处理抑制了HG暴露的系膜细胞中NF - κB的易位。
这些结果表明，五苓散对肾脏增殖、纤维化和炎症具有保护作用。因此，五苓散可能是针对导致糖尿病肾病的肾功能障碍的特异性疗法。
