Browning M C, Hsu C Y, Wang P L, Tune B M
J Infect Dis. 1983 Feb;147(2):341-51. doi: 10.1093/infdis/147.2.341.
The tubular necrosis produced by transient unilateral ischemia, three toxic cephalosporins, and the aminoglycoside neomycin were studied separately and in different combinations in the rabbit kidney. It was found that (1) mildly damaging transient ischemia (25 min) and a minimally toxic dose of the rapidly secreted cephalosporin cephaloglycin (60 mg/kg of body weight) are synergistically damaging; (2) there is no synergy between ischemia and the nonsecreted cephalosporin cephaloridine (90 mg/kg); and (3) ischemia and neomycin (100 mg/kg per day for three days) are not additively damaging, but the aminoglycoside has an additive effect with the combined insults of ischemia and cefazolin (500 mg/kg). Studies of transport showed that ischemia potentiates cephalosporin toxicity probably because it increases postischemic antibiotic concentrations in proximal tubular cells and that this increased uptake is the result of transiently augmented tubular secretion. Although this ischemic protocol reduced inulin clearance by 40%, it increased cephaloglycin secretion by an amount more than sufficient to overcome the decrease in filtration.
在兔肾中，分别研究了短暂单侧缺血、三种毒性头孢菌素和氨基糖苷类新霉素单独及不同组合所产生的肾小管坏死。结果发现：（1）轻度损伤性短暂缺血（25分钟）与快速分泌的头孢菌素头孢甘氨酸的最低毒性剂量（60毫克/千克体重）具有协同损伤作用；（2）缺血与非分泌型头孢菌素头孢噻啶（90毫克/千克）之间不存在协同作用；（3）缺血与新霉素（每天100毫克/千克，共三天）不存在相加损伤作用，但氨基糖苷类与缺血和头孢唑林（500毫克/千克）的联合损伤具有相加作用。转运研究表明，缺血增强头孢菌素毒性可能是因为它增加了缺血后近端肾小管细胞中的抗生素浓度，而这种摄取增加是肾小管分泌短暂增强的结果。尽管这种缺血方案使菊粉清除率降低了40%，但它使头孢甘氨酸分泌增加的量足以克服滤过减少的影响。
