中国组织工程研究 ›› 2011, Vol. 15 ›› Issue (44): 8175-8178.doi: 10.3969/j.issn.1673-8225.2011.44.002

• 肝移植 liver transplantation • 上一篇    下一篇

肝移植后缺血再灌注损伤大鼠诱导细胞凋亡中的一氧化氮

刘其雨,李  立,李晓延,陈  刚,赵英鹏,白建华,朱新锋   

  1. 昆明市第一人民医院暨昆明医学院附属甘美医院肝胆外科,云南省昆明市 650034
  • 收稿日期:2011-04-05 修回日期:2011-05-28 出版日期:2011-10-29 发布日期:2011-10-29
  • 作者简介:刘其雨☆,男,1982年生,江苏省淮安市人,汉族,昆明医学院在读博士,医师,主要从事器官移植方面研究。 liuqiyu_12@hotmail.com
  • 基金资助:

    云南省科技计划项目(2008CD195),课题名称:CYP3A5基因型在肝移植供受体匹配及术后FK506用药中的作用研究。昆明市科技计划项目(08S100304-2),课题名称:昆明器官移植研究中心建设。

Effects of nitric oxide on cell apoptosis induced by ischemia/reperfusion injury after liver transplantation in rats

Liu Qi-yu, Li Li, Li Xiao-yan, Chen Gang, Zhao Ying-peng, Bai Jian-hua, Zhu Xin-feng   

  1. Department of Hepatobiliary Surgery, First People’s Hospital of Kunming (Affiliated Ganmei Hospital of Kunming Medical College), Kunming 650034, Yunnan Province, China
  • Received:2011-04-05 Revised:2011-05-28 Online:2011-10-29 Published:2011-10-29
  • About author:Liu Qi-yu☆, Studying for doctorate, Physician, Department of Hepatobiliary Surgery, First People’s Hospital of Kunming (Affiliated Ganmei Hospital of Kunming Medical College), Kunming 650034, Yunnan Province, China liuqiyu_12@hotmail.com
  • Supported by:

    Science and Technology Plan Program of Yunnan Province, No.2008CD195*; Science and Technology Plan Program of Kunming City, No.08S100304-2*

摘要:

背景:由诱生型一氧化氮合酶产生的一氧化氮,是肝脏缺血再灌注损伤中病理生理学改变的一个重要因素。
目的:探讨一氧化氮在肝移植缺血再灌注诱导的肝细胞早期凋亡的影响以及相关基因caspase-3的表达情况。
方法:受体鼠72只随机数字表法均分成移植组、精氨酸组及L-硝基精氨酸甲酯组,均建立原位肝移植模型,后2组大鼠在开放血流前5 min于股静脉注射可升高血清一氧化氮水平的精氨酸或一氧化氮抑制剂L-硝基精氨酸甲酯。移植造模后剩余的24只大鼠设为假手术组。
结果与结论:血清谷草转氨酶活性比较,精氨酸组<移植组<L-硝基精氨酸甲酯组,组间比较差异有显著性意义(P < 0.01);血清一氧化氮浓度,精氨酸组>移植组>L-硝基精氨酸甲酯组;早期凋亡的高峰期为再灌注后3 h,肝细胞的活细胞数比例及肝组织中caspase-3的表达,精氨酸组<移植组< L-硝基精氨酸甲酯组。说明,一氧化氮对大鼠对肝移植缺血再灌注后肝细胞早期凋亡具有保护作用,且该作用可能主要通过下调caspase-3基因的表达。

关键词: 一氧化氮, 肝移植, 缺血再灌注损伤, 凋亡, 基因表达

Abstract:

BACKGROUND: Nitric oxide secreted by inducible nitric oxide synthase is one of important factors in the pathophysiological changes of the liver graft caused by ischemia/reperfusion injury.
OBJECTIVE: To investigate the effects of nitric oxide on the cell apoptosis induced by ischemia/reperfusion injury after liver transplantation in rats and the gene expression of caspase-3.
METHODS: Seventy-two recipient rats were randomly divided into transplantation, arginine and L-NAME groups, and they were developed into rat models of orthotopic liver transplantation. At 5 minutes before surgery, arginine, which can increase serum level of nitric oxide, and L-NAME, an inhibitor of nitric oxides were injected into the arginine and L-NAME groups, respectively. After model establishment, the remaining 24 rats were included into sham-surgery group.
RESULTS AND CONCLUSION: The activity of serum transaminase in the transplantation group was significantly higher than in the arginine group, but it was significantly lower than in the L-NAME group (P < 0.01). Serum level of nitric oxide in the transplantation group was higher than in the L-NAME group, but it was lower than in the arginine group. Early cell apoptosis peaked at 3 hours after reperfusion. The percentage of living hepatocytes and the expression of caspase-3 in the transplantation group were higher than in the arginine group, but it was lower than in the L-NAME group. These findings suggest that nitric oxide exhibits protective effects on early apoptosis of hepatocytes-induced by ischemia/reperfusion after orthotopic liver transplantation, which may be mediated by downregulating caspase-3 gene expression.

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