血红素加氧酶诱导在体外循环中的肾保护作用

目的 探讨血红素加氧酶-1(HO-1)在体外循环猪模型中的肾保护作用。方法 按常规方法以体重15kg左右约克猪建立体外循环时间共为3小时，其中主动脉阻断时间为1小时。共分为3个实验组：组1为单纯体外循环组；组2为血红素加氧酶-1抑制剂组；组3为血红素加氧酶-1诱导组。各组于术前至术后一小时检测尿NAG／Cr，并对术后一小时之肾组织进行光镜和电镜检查，了解肾组织损害情况。运用免疫组化方法检测HO-1的蛋白质在各组动物肾组织中的表达情况，并对免疫组化染色结果进行定量分析和统计学处理。另外用间接法测定各组HO-1活性。结果 与单纯体外循环组相比，HO-1诱导组肾功能受损较轻，光镜下与电镜下肾损害均有明显减轻，同时血红素加氧酶的活性和表达明显增高；加用HO-1抑制剂后，HO-1的活性下降，其肾保护效应被取消，且肾损害更为严重。结论 HO-1对体外循环后早期的肾功能具有保护作用，HO-1诱导可能成为一种新的有效的体外循环肾保护措施。

Renal protection by HO-1 induction in CPB porcine models

Objective: To examine the role of heme oxygenase-1 (HO-1) on renal protection in cardiopulmonary bypass porcine models. Methods: The extracorporeal circulation model was created routinely using pigs weighing around 15kg. Total CPB time for each animal was 3 hours, including one hour for aorto clamping. Three study groups were set: group one simply accepted CPB for 3 hours; animals in group two received HO-1 inhibitors; group three was pretreated with hemin to induce HO-1 before CPB. Urine NAG/Cr was measured preoperatively. Specimen of the kidney were taken at one hour postoperatively. Lesions in kidney constitutions were detected by pathological examination and electron microscope. The protein expressions of HO-1 were inspected by immunohistochemistry, while HO-1 activity was determined simultaneously. Results: Compared with group one, renal injuries were much more relieved in group three while observed under microscope and electron microscope; at the same time, their NAG/Cr levels were also lower. Meanwhile, the activity of HO-1 were much higher in group three than those in group one. In group two, HO-1 activity was inhibited, while levels of renal injury, were even higher than group one. Conclusions: HO-1 may play an important role in renal protection during CPB, induction of HO-1 may be used as a novel effective way for renal protection during cardiopulmonary bypass.