Hahn Oszkár, Szijártó Attila, Lotz Gábor, Schaff Zsuzsa, Vígváry Zoltán, Váli László, Kupcsulik Péter Károly
First Department of Surgery, Semmelweis University, Budapest, Hungary.
J Surg Res. 2007 Sep;142(1):32-44. doi: 10.1016/j.jss.2006.10.026. Epub 2007 Jul 12.
The purpose of this study was to increase the tolerance of the liver to radiation injury with the proven effect of ischemic precondition (IP) in decreasing oxygen-derived free radicals, and to compare the effect of intraoperative radiotherapy (IORT) during ischemia and during reperfusion on rat liver.
Two hundred fifty to 280 g male Wistar rats underwent 45 min of normothermic, segmental liver ischemia with or without IP/5 min ischemia and 10 min reperfusion, in two cycles. During ischemia or reperfusion, IORT doses of 0, 25, or 50 Gy were applied to the ischemic liver lobe. Hepatic microcirculation was monitored by laser Doppler flowmeter. Short- and long-term histological, alkaline phosphatase, bilirubin and tumor necrosis factor-alpha levels, liver tissue, and serum antioxidant alterations were measured.
Histological, laboratory, as well as flowmetry alterations caused by 25 Gy were reversible after 6 mo. Three mo following IORT, histological examination revealed parenchymal fibrosis, bridging, liver cell atrophy, and bile duct proliferation in the group that was irradiated with 50 Gy during reperfusion, without IP. In this group, the changes were present 6 mo following IORT, and also the levels of tumor necrosis factor-alpha and oxygen-derived free radicals after reperfusion were increased. All these changes were significantly milder in groups with IP, especially those that were irradiated during ischemia.
IORT to the liver, up to 25 Gy, can be applied without short- or long-term treatment morbidity. Doses of up to 50 Gy are tolerated with IP, which has never been described before. Irradiation during ischemia is less toxic for the liver tissue.
本研究的目的是利用缺血预处理（IP）在减少氧自由基方面已被证实的效果来提高肝脏对辐射损伤的耐受性，并比较术中放疗（IORT）在缺血期和再灌注期对大鼠肝脏的影响。
250至280克雄性Wistar大鼠接受45分钟的常温节段性肝缺血，伴有或不伴有IP（5分钟缺血和10分钟再灌注），共两个周期。在缺血或再灌注期间，对缺血肝叶给予0、25或50 Gy的IORT剂量。用激光多普勒血流仪监测肝微循环。测量短期和长期的组织学、碱性磷酸酶、胆红素和肿瘤坏死因子-α水平、肝组织以及血清抗氧化剂变化。
6个月后，25 Gy引起的组织学、实验室及血流测量变化是可逆的。IORT后3个月，组织学检查显示，在再灌注期间接受50 Gy照射且无IP的组中出现实质纤维化、桥接、肝细胞萎缩和胆管增生。在该组中，IORT后6个月仍存在这些变化，且再灌注后肿瘤坏死因子-α和氧自由基水平也升高。在有IP的组中，所有这些变化明显较轻，尤其是在缺血期接受照射的组。
对肝脏进行高达25 Gy的IORT，不会产生短期或长期治疗并发症。IP可耐受高达50 Gy的剂量，这在此前从未有过描述。缺血期照射对肝组织的毒性较小。
