Zager R A
Am J Physiol. 1986 Dec;251(6 Pt 2):F988-94. doi: 10.1152/ajprenal.1986.251.6.F988.
The purpose of this study was to assess the influence of Escherichia coli endotoxin on the evolution of ischemic acute renal failure (ARF). Rats were subjected to 25 min of bilateral renal artery occlusion (RAO) plus subcutaneous/intraperitoneal injections of either boiled E. coli or purified E. coli endotoxin (1.5 mg). Boiling the E. coli renders them nonviable but leaves endotoxin intact. Ischemic controls were injected with saline. The E. coli injections exacerbated ischemic ARF, doubling the degree of azotemia and increasing the extent of tubular necrosis and cast formation. This occurred without an adverse effect on renal blood flow or blood pressure during the initiation phase or maintenance phase of the ARF. Endotoxin tolerant rats were totally protected against the E. coli-ARF potentiating effect. Neither Staphylococcus aureus nor E. coli with denatured endotoxin adversely affected ischemic injury. Purified E. coli endotoxin reproduced the E. coli-ARF potentiating action. Neither E. coli nor purified endotoxin induced azotemia in the absence of renal ischemia.
E. coli endotoxin can exacerbate ischemic renal injury without compromising renal hemodynamics. This action appears to be mediated by an adverse effect of endotoxin on critical subcellular determinants of ischemic tissue injury.
本研究的目的是评估大肠杆菌内毒素对缺血性急性肾衰竭(ARF)进展的影响。将大鼠双侧肾动脉阻断(RAO)25分钟,并皮下/腹腔注射煮沸的大肠杆菌或纯化的大肠杆菌内毒素(1.5毫克)。煮沸大肠杆菌使其失去活性,但内毒素保持完整。缺血对照组注射生理盐水。注射大肠杆菌会加重缺血性ARF,使氮质血症程度加倍,并增加肾小管坏死和管型形成的程度。在ARF的起始阶段或维持阶段,这对肾血流量或血压没有不良影响。内毒素耐受的大鼠完全受到保护,免受大肠杆菌-ARF增强作用的影响。金黄色葡萄球菌或内毒素变性的大肠杆菌均未对缺血性损伤产生不利影响。纯化的大肠杆菌内毒素重现了大肠杆菌-ARF增强作用。在没有肾缺血的情况下,大肠杆菌和纯化的内毒素均未诱发氮质血症。
大肠杆菌内毒素可加重缺血性肾损伤,而不损害肾血流动力学。这种作用似乎是由内毒素对缺血组织损伤的关键亚细胞决定因素的不利影响介导的。