Stokes K Y, Abdih H K, Kelly C J, Redmond H P, Bouchier-Hayes D J
The Department of Surgery, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin.
Transplantation. 1996 Oct 27;62(8):1143-9. doi: 10.1097/00007890-199610270-00020.
Thermotolerance describes the process in which hyperthermia induces a transient resistance of the stressed cells to subsequent episodes of oxidative stress. The aims of this study were first, to assess the effect of ischemia-reperfusion (IR) injury on renal function and the expression of the ICAM-1 receptor and MHC antigens, and second, to evaluate the protective effects of thermotolerance on IR induced renal injury and its potential for decreasing allograft rejection, by decreasing alloantigen expression. Sprague-Dawley rats were randomized into three groups: control, IR, and hyperthermia + IR (HIR) (n=8 per group). Thermotolerance was induced 18 hr prior to IR by increasing the core body temperature to 41 degrees C+/-0.5 degrees C for 15 min. After left uninephrectomy, IR was induced by clamping the right renal pedicle for 45 min, followed by 2 hr reperfusion. Myeloperoxidase (MPO) activity was used as an indicator of renal neutrophil influx. Kidney edema was assessed using the weight difference between left and right kidneys. Renal function was evaluated by measuring serum creatinine and urea 2 hr following clamp removal. Immunocytochemistry was used to measure expression of ICAM-1 and MHC antigen. Renal function was significantly impaired by IR with serum creatinine and urea levels of 131.5+/-5.01 microM and 11.2+/-0.71 mM, respectively, compared with controls of 67.9+/-5.11 microM and 8.1+/-0.36 mM, P<0.005 in both cases. Renal function was preserved in the HIR group, serum creatinine (84.8+/-8.58 microM) and urea (9.0+/-0.52 mM) were comparable to that of controls. Renal endothelium was activated in the IR group compared with controls, with increased ICAM-1, and tubular epithelium showed increased class II MHC expression. This up-regulation was prevented by prior induction of thermotolerance. Endothelial permeability was increased in the IR group with MPO activity of 0.8+/-0.08 units/g tissue--twice that of control levels P<0.05--and a marked increase in organ edema. Thermotolerance preserved endothelial barrier function. Thermotolerance may prevent IR injury by preventing endothelium activation and has the potential to modify allograft rejection by decreasing expression of ICAM-1, an important T cell receptor, and class II MHC.
热耐受描述的是高温诱导应激细胞对随后的氧化应激发作产生短暂抗性的过程。本研究的目的，一是评估缺血再灌注（IR）损伤对肾功能以及细胞间黏附分子-1（ICAM-1）受体和主要组织相容性复合体（MHC）抗原表达的影响；二是通过降低同种异体抗原表达，评估热耐受对IR诱导的肾损伤的保护作用及其降低同种异体移植排斥反应的潜力。将Sprague-Dawley大鼠随机分为三组：对照组、IR组和热疗+IR组（HIR组）（每组n = 8）。在IR前18小时，通过将核心体温升至41℃±0.5℃并持续15分钟来诱导热耐受。左肾切除术后，通过夹闭右侧肾蒂45分钟诱导IR，随后再灌注2小时。髓过氧化物酶（MPO）活性用作肾中性粒细胞流入的指标。使用左右肾重量差异评估肾水肿。在夹闭解除后2小时，通过测量血清肌酐和尿素来评估肾功能。采用免疫细胞化学法检测ICAM-1和MHC抗原的表达。与对照组血清肌酐和尿素水平分别为67.9±5.11μM和8.1±0.36 mM相比，IR显著损害肾功能，血清肌酐和尿素水平分别为131.5±5.01μM和11.2±0.71 mM，两种情况P均<0.005。HIR组肾功能得以保留，血清肌酐（84.8±8.58μM）和尿素（9.0±0.52 mM）与对照组相当。与对照组相比，IR组肾内皮细胞被激活，ICAM-1增加，肾小管上皮细胞II类MHC表达增加。预先诱导热耐受可防止这种上调。IR组内皮通透性增加，MPO活性为0.8±0.08单位/克组织，是对照水平的两倍（P<0.05），器官水肿明显增加。热耐受保留了内皮屏障功能。热耐受可能通过防止内皮细胞激活来预防IR损伤，并且有可能通过降低重要的T细胞受体ICAM-1和II类MHC的表达来改变同种异体移植排斥反应。
