Szijártó Attila
Semmelweis Egyetem I. sz. Sebészeti Klinika 1082 Budapest Ulloi út 78.
Magy Seb. 2008 Jun;61(3):128-35. doi: 10.1556/MaSeb.61.2008.3.5.
The author evaluates an experimental model of hepatic resection. The goal of the study was to investigate ischaemic tolerance during liver resection. In this model, we also investigated the protective effects of ischemic preconditioning (IP), a PARP enzyme inhibitor (PJ-34), and an antioxidant glutamine (Gln). Inbred male Wistar rats were used for the experiments. Complete segmental ischaemia of the liver was achieved with or without using IP, PJ-34 or Gln pretreatment before the ischaemia. Microcirculation was monitored using laser Doppler flowmeter (LDF) throughout the ischaemia-reperfusion period. Required standardizations and mathematical analyses were performed in order to validate statistical analysis. Histological changes, immunohistochemistry (TUNEL, caspase), liver enzymes, bilirubin, and TNF-alpha levels were all measured simultaneously.
RESULTS, CONCLUSION: 30 minutes ischaemia was well tolerated by the liver and IP does not cause further improvement. 45 to 60 minutes ischaemia resulted in serious microcirculatory changes during reperfusion. 90 minutes ischaemia was unequivocally intolerable. The liver injury and microcirculatory changes caused by 45 or 60 minutes of ischemia could be reduced with IP. Improvement was observed both on histology and in survival rates. After 45 and 60 minutes, IP + I-R caused a significant decline in the TNF-alpha levels. IP, PJ-34 PARP-inhibitor and glutamine pretreatment prior to 60 minutes of ischaemia resulted in an improvement of microcirculation. Immunohistochemistry for activated caspase-3 demonstrated significantly higher apoptosis rates in the PJ-34 PARP-inhibitor and glutamine-pretreated groups, in contrast to the sham and I-R groups. Antioxidant levels in the serum and in the liver homogenates showed significant improvement in the IP and glutamine-pretreated groups.
作者评估了肝切除的实验模型。该研究的目的是调查肝切除期间的缺血耐受性。在这个模型中，我们还研究了缺血预处理（IP）、聚腺苷酸核糖聚合酶（PARP）酶抑制剂（PJ - 34）和抗氧化剂谷氨酰胺（Gln）的保护作用。近交系雄性Wistar大鼠用于实验。在缺血前，使用或不使用IP、PJ - 34或Gln预处理实现肝脏的完全节段性缺血。在整个缺血再灌注期间，使用激光多普勒血流仪（LDF）监测微循环。进行了必要的标准化和数学分析以验证统计分析。同时测量组织学变化、免疫组织化学（TUNEL、半胱天冬酶）、肝酶、胆红素和肿瘤坏死因子 - α水平。
结果、结论：肝脏对30分钟缺血耐受性良好，IP未带来进一步改善。45至60分钟缺血导致再灌注期间出现严重的微循环变化。90分钟缺血明显无法耐受。IP可减轻45或60分钟缺血所致的肝损伤和微循环变化。组织学和生存率均有改善。45和60分钟后，IP + 缺血再灌注导致肿瘤坏死因子 - α水平显著下降。在60分钟缺血前进行IP、PJ - 34 PARP抑制剂和谷氨酰胺预处理可改善微循环。与假手术组和缺血再灌注组相比，PJ - 34 PARP抑制剂和谷氨酰胺预处理组活化半胱天冬酶 - 3的免疫组织化学显示凋亡率显著更高。IP组和谷氨酰胺预处理组血清和肝脏匀浆中的抗氧化剂水平有显著改善。
