Hayashi K, Nagamatsu T, Honda S, Suzuki Y
Department of Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Eur J Pharmacol. 1996 Dec 5;316(2-3):297-306. doi: 10.1016/s0014-2999(96)00689-9.
The antinephritic effects of butein (3,4,2',4'-tetrahydroxychalcone) on original-type anti-glomerular basement membrane antibody-associated glomerulonephritis in rats were investigated. Butein was given to anti-glomerular basement membrane antibody-associated glomerulonephritic rats for 15 days after the induction of nephritis. Butein prevented proteinuria and histological alterations. The up-regulation of intercellular adhesion molecule-1 (ICAM-1) expression and increase in leukocyte function-associated antigen-1 (LFA-1) positive cells in nephritic glomeruli significantly declined with butein treatment. In the further investigation to clarify the effects of butein on ICAM-1 expression, human umbilical vein endothelial cells were treated with butein in the presence of tumor necrosis factor-alpha (TNF-alpha) or phorbol 12-myristate 13-acetate (PMA). Butein prevented the up-regulation of ICAM-1 expression mediated by TNF-alpha or PMA on human umbilical vein endothelial cells in a dose-dependent manner. When human umbilical vein endothelial cells or neutrophils were treated with butein, the adhesion of neutrophils to human umbilical vein endothelial cells was suppressed. These data suggest that the antinephritic action of butein is due to inhibition of intraglomerular accumulation of leukocytes through the prevention of the up-regulation of ICAM-1 and the inhibition of a function of adhesion molecules on the surface of leukocytes.
研究了白杨素（3,4,2',4'-四羟基查尔酮）对大鼠原发性抗肾小球基底膜抗体相关肾小球肾炎的抗肾炎作用。在诱导肾炎后，给抗肾小球基底膜抗体相关肾小球肾炎大鼠给予白杨素，持续15天。白杨素可预防蛋白尿和组织学改变。经白杨素治疗后，肾炎性肾小球中细胞间黏附分子-1（ICAM-1）表达上调及白细胞功能相关抗原-1（LFA-1）阳性细胞增多的情况显著减轻。在进一步研究白杨素对ICAM-1表达的影响时，在存在肿瘤坏死因子-α（TNF-α）或佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）的情况下，用白杨素处理人脐静脉内皮细胞。白杨素以剂量依赖的方式阻止TNF-α或PMA介导的人脐静脉内皮细胞ICAM-1表达上调。当用人脐静脉内皮细胞或中性粒细胞处理白杨素时，中性粒细胞与人脐静脉内皮细胞的黏附受到抑制。这些数据表明，白杨素的抗肾炎作用是由于通过防止ICAM-1上调以及抑制白细胞表面黏附分子的功能来抑制白细胞在肾小球内的积聚。
