Simpson L O, Aarons I, Howie J B
Br J Exp Pathol. 1979 Feb;60(1):45-57.
NZB x OUW F1 hybrid mice were treated with thiamphenicol at 25, 50 and 250 mg/kg/day from the time of their first positive antinuclear antibody test until their death. Untreated mice fed the same diet served as controls with body weight, mortality and renal disease patterns conforming to published reports of the biology of the BW mice. Regular testing of urine and bloodm and detailed postmortem examinations showed (a) that with increasing drug dose levels heavy proteinuria was almost eliminated and blood urea concentrations significantly lowered; (b) that in treated and untreated mice moderate to severe anaemia developed, apparently unrelated to the degree of uraemia; (c) that changes in renal function did not correlate with antinuclear antibody activity, nor did the drop in packed cell volume correlate with fixed or free circulating antierythrocyte autoantibody positivity; (d) that histological analysis of renal changes showed that at the highest dose level glomerular lesions were minimal. Thus the prolonged treatment with thiamphenicol reduced the severity of the spontaneous renal disease and resulted in a significant extension of lifespan.
从首次抗核抗体检测呈阳性起,将NZB x OUW F1杂交小鼠每日按25、50和250毫克/千克的剂量用甲砜霉素进行治疗,直至其死亡。喂食相同饮食的未治疗小鼠作为对照,其体重、死亡率和肾病模式与已发表的BW小鼠生物学报告相符。定期对尿液和血液进行检测,并进行详细的尸检,结果显示:(a) 随着药物剂量水平的增加,重度蛋白尿几乎消除,血尿素浓度显著降低;(b) 治疗组和未治疗组小鼠均出现中度至重度贫血,这显然与尿毒症程度无关;(c) 肾功能变化与抗核抗体活性无关,红细胞压积下降也与固定或游离循环抗红细胞自身抗体阳性无关;(d) 肾脏变化的组织学分析表明,在最高剂量水平时,肾小球病变最小。因此,甲砜霉素的长期治疗降低了自发性肾病的严重程度,并显著延长了寿命。