肝脏肿瘤缺血再灌注损伤后NO和NOS的改变及意义

Changes of NO and NOS after ischemia reperfusion injury of hepatic neoplasm and its implications

目的 :研究肝脏肿瘤缺血再灌注后正常肝脏和肿瘤组织中一氧化氮 (NO)和一氧化氮合酶 (NOS)的改变 ,探讨缺血再灌注对肿瘤组织的影响及其意义 .方法 :通过超声引导将VX2肿瘤组织混悬液穿刺注射到新西兰兔肝脏左中叶 ,建立肝脏肿瘤模型 ,用无损伤血管钳阻断肿瘤所在肝叶的肝动脉分支 6 0min ,然后去除血管阻断恢复血流 ,并随机将模型动物分为缺血再灌注前 (对照 )、缺血再灌注后 0min ,1h ,1d ,3d ,7d 6个时间组 ,取肝脏组织和肿瘤组织 ,分别测定NO和NOS的含量 .结果 :肝脏组织中的NO含量除缺血再灌注 1h升高外 ,其余各时间点均低于正常水平 ,变化幅度较小 ;肿瘤组织的NO含量于缺血再灌注后 0min开始下降 ,1h降到最低 (P <0 .0 1 ) ,随后又有所升高 ,但至 7d时仍明显低于正常水平 (P <0 .0 1 ) .肝脏组织的总NOS含量于 0min时有所降低 ,但随后恢复 ,变化幅度较小 ,而iNOS含量 0min至 1d明显下降 (P <0 .0 1 ) ,其后有所恢复 ,但仍未达正常水平 ;肿瘤组织的总NOS含量 0min开始下降 ,0min至 1h低于正常水平 ,随后开始升高 ,1～ 7d明显高于正常 (P <0 .0 1 ) ,其中iNOS含量持续上升 ,至 7d明显高于正常水平 (P <0 .0 1 ) .结论 :缺血再灌注对肿瘤组织的损伤明显高于肝脏组织 。

AIM: To analyze the changes of nitric oxide (NO) and nitric oxide synthase (NOS) after ischemia reperfusion injury of the normal liver and neoplasm and to explore the influence of the ischemia reperfusion on the hepatic neoplasm. METHODS: Hepatic neoplasm animal model was established by ultrasonography guided implantation of VX 2 tumor constitution mass into the left middle lobe of liver of the rabbits. Ischemia was caused by using a non traumatic vascular clamp to block the branches in the left middle lobe of the hepatic artery for 60 min, and then the clamp was removed and the reperfusion injury of the hepatic neoplasm occurred. The animal models were randomly divided into the control group (before ischemia and reperfusion), and 0 min, 1 h, 1 d, 3 d and 7 d groups after ischemia reperfusion, and then their normal and hepatic neoplasm tissues were harvested to detect NO and NOS respectively. RESULTS: NO concentration of hepatic tissue of all groups except 1 h group was lower than that in control group and changed a little. The NO concentration of neoplasm tissue decreased after ischemia reperfusion and reached the lowest level at 1 h and then restored gradually, but retained the lower level than that in the control group at 7 d( P < 0.01). The NOS concentration of hepatic tissue including eNOS, nNOS and iNOS decreased a little, but iNOS concentration decreased apparently from 0 min to 1 h ( P <0.01), however, it did not restore to the normal level of control group at 7 d yet. The NOS concentration of neoplasm tissue first decreased below the normal level at 0 min and then rose over it from 1 d to 7 d( P <0.01), but iNOS concentration rose continuously and beyond the normal level after ischemia reperfusion injury from 0 min to 7 d ( P < 0.01). CONCLUSION: Neoplasm tissue is injured much more than hepatic tissue after ischemia reperfusion; NO play an injurious roles during the process of ischemia reperfusion of neoplasm tissue; and iNOS is the key modulator in producing NO of the neoplasm.