Chiang C-K, Sheu M-L, Hung K-Y, Wu K-D, Liu S-H
Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Kidney Int. 2006 Aug;70(4):682-9. doi: 10.1038/sj.ki.5001617.
Glomerulonephritis (GN) is still the most common cause of end-stage renal disease. Accumulation of glomerular macrophages, proliferation of mesangial cells, and deposition of extracellular matrix proteins are pathobiological hallmarks of GN. Pharmacological interventions that can inhibit these insults may be beneficial in the retardation of the progression of GN. Honokiol originally isolated from Magnolia officinalis, shows antioxidative, anti-inflammatory, and antiproliferative activities in a variety of inflammation models. In this study, we first investigated the in vivo effects of honokiol on rat anti-Thy1 nephritis. Anti-Thy1 nephritis was induced in Wistar rats by injecting mouse anti-rat Thy1 antibodies intravenously. Nephritic rats were randomly assigned to receive honokiol (2.5 mg/kg, twice a day) or vehicle and were killed at various time points. Glomerular histology and immunohistopathology and urine protein excretion were studied. Western blotting was conducted for markers of proliferation. Adhesion molecules, chemokine, and extracellular matrix gene expression were evaluated by Northern blotting. Honokiol-treated nephritic rats excreted less urinary protein and had lower glomerular cellularity and sclerosis. The increased intraglomerular proliferating cell nuclear antigen and Akt phosphorylation in nephritic rats could be abolished by the treatment of honokiol. Honokiol also alleviated glomerular monocyte chemoattractant protein-1 and intracellular adhesion molecule-1, similar to type I (alpha1) collagen and fibronectin mRNA levels of nephritic rats. These results indicate that honokiol may have therapeutic potential in mesangial proliferative GN.
肾小球肾炎（GN）仍是终末期肾病最常见的病因。肾小球巨噬细胞积聚、系膜细胞增殖以及细胞外基质蛋白沉积是GN的病理生物学特征。能够抑制这些损伤的药物干预可能有助于延缓GN的进展。厚朴酚最初是从厚朴中分离出来的，在多种炎症模型中显示出抗氧化、抗炎和抗增殖活性。在本研究中，我们首先研究了厚朴酚对大鼠抗Thy1肾炎的体内作用。通过静脉注射小鼠抗大鼠Thy1抗体在Wistar大鼠中诱导抗Thy1肾炎。将肾炎大鼠随机分为接受厚朴酚（2.5mg/kg，每日两次）或赋形剂组，并在不同时间点处死。研究了肾小球组织学、免疫组织病理学和尿蛋白排泄情况。对增殖标志物进行了蛋白质印迹分析。通过Northern印迹法评估黏附分子、趋化因子和细胞外基质基因表达。接受厚朴酚治疗的肾炎大鼠尿蛋白排泄减少，肾小球细胞数量和硬化程度降低。厚朴酚治疗可消除肾炎大鼠肾小球内增殖细胞核抗原和Akt磷酸化的增加。厚朴酚还减轻了肾小球单核细胞趋化蛋白-1和细胞间黏附分子-1，类似于肾炎大鼠I型（α1）胶原和纤连蛋白的mRNA水平。这些结果表明厚朴酚在系膜增生性GN中可能具有治疗潜力。
