Gentamicin nephrotoxicity in the setting of acute renal hypoperfusion.
Gentamicin nephrotoxicity in the setting of acute renal hypoperfusion.
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急性肾低灌注情况下的庆大霉素肾毒性。
DOI：
10.1152/ajprenal.1988.254.4.f574
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Zager,RA
中科院分区：
文献类型：
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作者：
Zager,RA
本研究的目的是评估急性肾灌注不足和氨基糖苷类药物肾毒性之间的相互作用。通过肾上部分主动脉收缩在大鼠中产生1小时的肾灌注不足（55-60 mmHg;肾血流量1.6 +/-0.13 ml/min）。在低灌注期开始时给予庆大霉素120 mg/kg。单独接受庆大霉素或单独接受低灌注的大鼠作为对照。仅低灌注诱导轻度S3近端肾小管刷状缘膜起泡，但未引起尿酶、氮质血症或肾小管坏死。单独庆大霉素未引起氮质血症或肾小管坏死。然而，在低灌注期间注射庆大霉素引起严重氮质血症（血尿素氮94 +/- 16;肌酐1.74 +/- 0.22 mg/dl）和广泛的S3近端肾小管坏死，而不影响肾灌注。S1和S2管段，庆大霉素毒性的主要目标，表现出最小的损害。低灌注增加肾脏对庆大霉素的摄取，但在对照组中没有引起肾损害。总之，庆大霉素可加速低灌注诱导的急性肾功能衰竭。这种效应似乎是由于S3细胞毒性效应，将亚致死性缺血性S3肾小管损伤转化为明显的细胞坏死。
The purpose of this study is to assess interactions between acute renal hypoperfusion and aminoglycoside nephrotoxicity. One hour of renal hypoperfusion (55–60 mmHg; renal blood flow 1.6 +/- 0.13 ml/min) was created in rats by suprarenal partial aortic constriction. Gentamicin, 120 mg/kg, was given at the start of the hypoperfusion period. Rats that either received gentamicin alone or were subjected to hypoperfusion alone served as controls. Hypoperfusion alone induced mild S3 proximal tubular brush-border membrane blebbing, but it caused no enzymuria, azotemia, or tubular necrosis. Gentamicin alone induced no azotemia or tubular necrosis. However, gentamicin injected during hypoperfusion caused severe azotemia (blood urea nitrogen 94 +/- 16; creatinine 1.74 +/- 0.22 mg/dl) and extensive S3 proximal tubular necrosis without affecting renal perfusion. S1 and S2 tubular segments, the major targets of gentamicin toxicity, showed minimal damage. Hypoperfusion increased renal gentamicin uptake, but matching it in control rats induced no renal damage. In conclusion, gentamicin can precipitate hypoperfusion-induced acute renal failure. This effect appears to be due to an S3 cytotoxic effect, which converts sublethal ischemic S3 tubular injury into overt cell necrosis.