McClurkin C, Phan S H, Hsu C H, Patel S R, Spicker J K, Kshirsagar A M, Yuan W Y, Wiggins R C
Department of Internal Medicine, School of Public Health, University of Michigan, Ann Arbor.
J Am Soc Nephrol. 1990 Sep;1(3):257-65. doi: 10.1681/ASN.V13257.
A rabbit model of renal glomerulosclerosis induced by anti-glomerular basement membrane antibody was used to determine whether colchicine would protect renal function and reduce fibrosis. Initial studies established the time course of renal function changes and fibrosis. Colchicine at a dose of 0.02 to 0.04 mg/kg per day injected ip was begun at day 4 when injury had been initiated, and the experiment was ended at day 21 when fibrotic changes were established. Colchicine significantly reduced the rise in serum creatinine (serum creatinine = 2.7 +/- 0.3 mg% in vehicle-treated animals versus 1.8 +/- 0.1 mg% in colchicine-treated animals) and interstitial fibrosis (fibrosis score = 2.6 +/- 0.2 in vehicle-treated versus 1.5 +/- 0.2 in colchicine-treated animals). Colchicine treatment did not significantly affect weight, anti-guinea pig immunoglobulin level, % fibrocellular crescents formed, hydroxyproline per gram (dry weight) in tissue, or urine protein: creatine ratio. Regression analysis was performed to examine the interrelationships between variables for all animals and the effect of colchicine on pairs of variables. No clear-cut site of colchicine action could be identified. These data show that colchicine, in doses that could be used in humans, protected renal function by about 25% and reduced interstitial fibrosis in a model of severe crescentic nephritis.
采用抗肾小球基底膜抗体诱导的兔肾小球硬化模型，以确定秋水仙碱是否能保护肾功能并减少纤维化。初步研究确定了肾功能变化和纤维化的时间进程。当损伤开始后的第4天开始腹腔注射每天剂量为0.02至0.04mg/kg的秋水仙碱，并在第21天纤维化改变确立时结束实验。秋水仙碱显著降低了血清肌酐的升高（载体处理组动物血清肌酐为2.7±0.3mg%，而秋水仙碱处理组动物为1.8±0.1mg%）以及间质纤维化（载体处理组纤维化评分为2.6±0.2，秋水仙碱处理组为1.5±0.2）。秋水仙碱处理对体重、抗豚鼠免疫球蛋白水平、形成的纤维细胞性新月体百分比、组织中每克（干重）羟脯氨酸或尿蛋白：肌酐比值均无显著影响。进行回归分析以检查所有动物变量之间的相互关系以及秋水仙碱对成对变量的影响。未发现秋水仙碱作用的确切位点。这些数据表明，在可用于人类的剂量下，秋水仙碱在严重新月体性肾炎模型中可保护约25%的肾功能并减少间质纤维化。
