苦参碱防治肝血窦内皮细胞冷缺血-再灌注损伤

Matrine protects sinusoidal endothelial cells from cold ischemia and reperfusion injury in rat orthotopic liver transplantation

目的:探讨苦参碱对大鼠原位肝移植中肝血窦内皮细胞冷缺血再灌注损伤的保护作用及其机制。方法:应用大鼠原位肝移植模型,供肝保存5h,168只大鼠随机分为对照组、小剂量治疗组、大剂量治疗组和假手术组,分别检测移植术后1、2、4、24h血透明质酸(HA)、一氧化氮(NO)、肿瘤坏死因子α(TNFα)及肝组织丙二醛(MDA)、超氧化物歧化酶(SOD)、细胞间黏附分子1(ICAM1)的含量,并观察肝血窦内皮细胞形态学的改变。结果:与对照组比较,治疗组术后各时间点的HA和ICAM1表达均显著减少,NO含量增加,TNFα、MDA、SOD水平均明显降低,肝血窦内皮细胞形态出现改善。结论:苦参碱对大鼠原位肝移植冷缺血再灌注中肝血窦内皮细胞损伤具有保护作用。

Objective:To study the role and mechanism of matrine in preventing cold ischemia and reperfusion injury of sinusoidal endothelial cells (SEC) in rat orthotopic liver transplantation (OLT). Methods:168 syngeneic SD rats were randomly divided into four groups: untreated group, low-dose treated group, high-dose treated group and pseudo-treated group. After 5 hours of preservation in Ringer's (LR) solution, orthotopic implantation of the donor liver was performed. At 1 h, 2 h, 4 h and 24 h after reperfusion, 6 rats were killed in each group to collect the serum and the median lobe of liver for assay.Results: In both treated groups, the level of hylluronic acid (HA) and intercellular adhesion molecule-1 (ICAM-1) decreased significantly at different times post-transplantation, and the pathological changes of SEC ameliorated, too. Matrine markedly inhibited the activation of Kupffer cells and their release of tumor necrosis factor (TNF), and suppressed the hepatic malondialdehyde (MDA) level and the activity of superoxide dismutase (SOD). Conclusion:Matrine can prevent SEC from cold ischemia and reperfusion injury in rat orthotopic liver transplantation.