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| 青藤碱对大鼠原位肝移植缺血再灌注损伤的保护作用 |
| 林峰1,慕宁1,王海梁1,傅宏1,王正昕1,王全兴2,丁国善1,傅志仁1* |
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| (1.第二军医大学长征医院全军器官移植研究所,上海 200003*2.第二军医大学基础部免疫学教研室,免疫学研究所,上海 200433) |
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| 摘要: |
| 目的:探讨青藤碱对大鼠原位肝移植缺血再灌注损伤的保护作用。方法:采用Kamada’s“二袖套法”建立SD→SD大鼠原位肝移植模型,随机分为假手术组、对照组、低剂量(40 mg/kg)和高剂量(80 mg/kg)青藤碱组,分别观察移植术后1周存活率,检测术后2、6、12、24 h血清ALT,TUNEL法检测肝细胞凋亡指数(AI),RT-PCR检测肝脏组织中的TNF-α、IL-1β mRNA的含量,并观察移植肝脏病理学改变。结果:与对照组比较,青藤碱低剂量、高剂量组术后1周存活率显著提高(75%、75% vs 12.5%,P<0.01);在各个时间点,青藤碱治疗组的ALT水平明显低于对照组(P<0.01),肝组织中的TNF-α、IL-1β mRNA表达与对照组相比均显著降低(P<0.01),肝脏病理学形态也明显改善。结论:青藤碱可以通过抑制TNF-α、IL-1β等炎症性细胞因子合成,抑制肝细胞凋亡,减轻肝细胞及肝窦内皮细胞的损伤,达到保护肝移植缺血再灌注损伤的效果。 |
| 关键词: 原位肝移植 青藤碱 大鼠 缺血再灌注损伤 细胞凋亡 细胞因子 |
| DOI：10.3724/SP.J.1008.2008.01433 |
| 投稿时间：2008-05-07修订日期：2008-06-14 |
| 基金项目: |
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| Protective effect of sinomenine on ischemia-reperfusion injury during orthotopic liver transplantation in rats |
| LIN Feng1,MU Ning1,WANG Hai-liang1,FU Hong1,WANG Zhen-xin1,WANG Quan-xing2,DING Guo-shan1,FU Zhi-ren1* |
| (1.Organ Transplantation Institute of PLA,Changzheng Hospital,Second Military Medical University,Shanghai 200003,China* 2.Immunity Research Institute,College of Basic Medical Sciences,Second Military Medical University,Shanghai 200433) |
| Abstract: |
| Objective:To investigate the protective effect of sinomenine on the cold ischemia/reperfusion injury during orthotopic liver transplantation (OLT) in rats.Methods: OLT were performed in normal rats using Kamada’s two-cuff technique.The rats were randomly divided into sham operation,control and two sinomenine groups.Animals in sinomenine groups were treated with low (40 mg/kg) or high dose (80 mg/kg) of sinomenine.The serum and tissue samples of rats in each group were collected 2,6,12, and 24 h after reperfusion,and the one-week survival rate was observed.The apoptosis index (AI) of liver cells after OLT was detected by TUNEL.The expression of TNF-α and IL-1β mRNA in the liver were detected by RT-PCR.Results: Compared with the control group,the level of ALT was significantly decreased in the two sinomenine treatment groups at different time points after transplantation,and their one-week survival rates were also significantly increased (75%,75% vs 12.5%,P<0.01).Compared with the control group,the AI of liver cells was markedly decreased in sinomenine treatment groups (P<0.01).Sinomenine treatment also significantly decreased the expression of TNF-α and IL-1β mRNA (P<0.01) and greatly ameliorated the focal necrosis of hepatocytes and sinusoidal endothelial cells (SECs).Conclusion: Sinomenine can inhibit hepatocyte apoptosis by inhibiting the synthesis of TNF-α and IL-1β.sinomenine can prevent hepatic cells and SECs from cold ischemia/reperfusion injury during orthotopic liver transplantation in rats. |
| Key words: orthotopic liver transplantation sinomenine rats ischemia and reperfusion injury apoptosis cytokines |
