中国组织工程研究 ›› 2012, Vol. 16 ›› Issue (53): 9898-9902.doi: 10.3969/j.issn.2095-4344.2012.53.004

• 肝移植 liver transplantation • 上一篇    下一篇

三氯化钆对移植肝缺血再灌注损伤的保护作用

权 虎1,贺志军2,左朝辉1,欧阳永忠1,许 幂3,汤 明1,唐 卫1,王懿春1   

  1. 1湖南省肿瘤医院胃十二指肠胰腺外科,湖南省长沙市 410013
    2中南大学湘雅二医院普外器官移植科,湖南省长沙市 410011
    3湖南省人民医院肝胆外科,湖南省长沙市 410005
  • 收稿日期:2012-03-19 修回日期:2012-05-15 出版日期:2012-12-30 发布日期:2012-12-30
  • 通讯作者: 贺志军,博士,教授,主任医师,硕士生导师,中南大学湘雅二医院普外器官移植科,湖南省长沙市 410011
  • 作者简介:权虎★,男,1979年生,湖南省岳阳市人,汉族,2009年中南大学毕业,硕士,医师,主要从事腹部外科研究。 Quanhu2009@sina.com

Protective effect of gdolinium chloride against ischemia-reperfusion injury to the transplanted liver

Quan Hu1, He Zhi-jun2, Zuo Chao-hui1, Ouyang Yong-zhong1, Xu Mi3, Tang Ming1, Tang Wei1, Wang Yi-chun1   

  1. 1Department of Gastroduodenal Pancreatic Surgery, Hunan Provincial Tumor Hospital, Changsha 410011, Hunan Province, China
    2Department of Organ Transplantation of General Surgery, the Xiangya Second Hospital of Central South University, Changsha 410011, Hunan Province, China
    3Department of Hepatobiliary Surgery, Hunan People's Hospital, Changsha 410011, Hunan Province, China
  • Received:2012-03-19 Revised:2012-05-15 Online:2012-12-30 Published:2012-12-30
  • Contact: He Zhi-jun, Doctor, Professor, Chief physician, Master’s supervisor, Department of Organ Transplantation of General Surgery, the Xiangya Second Hospital of Central South University, Changsha 410011, Hunan Province, China
  • About author:Quan Hu★, Master, Physician, Department of Gastroduodenal Pancreatic Surgery, Hunan Provincial Tumor Hospital, Changsha 410011, Hunan Province, China Quanhu2009@sina.com

摘要:

背景:三氯化钆能抑制枯否细胞的活化,降低其吞噬活性,并减少枯否细胞激活后的肿瘤坏死因子α及白细胞介素1 释放,从而减轻肝脏缺血再灌注损伤。
目的:观察三氯化钆对大鼠移植肝缺血再灌注损伤的影响并探讨其作用机制。
方法:供、受体均采用雄性SD大鼠,将实验动物随机分为3组。采用改良连续缝合进行肝上下腔静脉重建的Kamada’s“两袖套法”建立大鼠肝移植模型。①假手术组:不行肝移植,游离肝脏、结扎静脉后关腹,不处理及用药。②生理盐水组:热缺血时间0-5 min,供肝冷保存时间为2 h,移植前连续3 d 经尾静脉向受鼠注射生理盐水,移植后再经尾静脉注射生理盐水1次。③三氯化钆组:热缺血时间为0-5 min,冷保存时间为2 h,移植前连续3 d 经尾静脉向受鼠注射0.5%三氯化钆,移植后再经尾静脉注射0.5%三氯化钆1次。24 h后处死大鼠进行相应指标检测。
结果与结论:与假手术组比较,三氯化钆组、生理盐水组血清丙氨酸转氨酶、谷氨酸转氨酶、碱性磷酸酶、γ-谷氨酰转移酶水平明显升高(P < 0.05);三氯化钆组各指标较生理盐水组有所减轻(P < 0.05)。病理组织学检查发现生理盐水组、三氯化钆组病变范围及缺血再灌注损伤程度均较假手术组明显增加。与生理盐水组比较,三氯化钆组血清白细胞介素1、肿瘤坏死因子α及凋亡指数明显降低(P < 0.05),淤血、空泡变性及坏死Suzuki’s评分均较低(P < 0.05)。提示三氯化钆在一定程度上是通过封闭枯否细胞吞噬并抑制细胞因子的释放实现对移植肝缺血再灌注损伤的保护机制。

关键词: 肝移植, 再灌注损伤, 三氯化钆, 枯否细胞, 白细胞介素1, 肿瘤坏死因子α

Abstract:

BACKGROUND: Gadolinium chloride can inhibit the Kupffer cell activation, reduce their phagocytic activity, and reduce tumor necrosis factor alpha and interleukin 1 release after Kupffer cell activation, thereby alleviate the ischemia-reperfusion injury of liver.
OBJECTIVE: To study the effect of gdolinium chloride on ischemia-reperfusion injury of rat receptor’s liver and to explore the mechanism.
METHODS: Donors and receptors were all male Sprague Dawley rats which were randomly divided into three groups. The modified Kamada’s two-cuff technique was used to build rat liver transplantation model through liver superior and inferior vena cava reconstruction by modified continuous suture. In the sham-operation group, the rats were treated without liver transplantation, the liver was freed and the abdomen was closed after vein ligation without treatment and received drug administration. In the saline group, the warm ischemia time was 0-5 minutes and cold preservation time of the donor liver was 2 hours, the saline was injected into the rats via the tail vein for 3 days before implantation, and after implantation, the saline was injected into the rats once more. In the gadolinium chloride group, the warm ischemia time was 0-5 minutes and cold preservation time of the donor liver was 2 hours, 0.5% gadolinium chloride was injected into the rats via the tail vein for 3 days before implantation, and after implantation, the injection was performed once more. The rats were sacrificed after 24 hours for the corresponding index detection.
RESULTS AND CONCLUSION: Compared with sham-operation group, the serum alanine aminotransferase, alanine aminotransferase, alkaline phosphatase and γ-gamma-glutamyl transferase levels were increased significantly in gadolinium chloride and saline groups (P < 0.05); all the indexes in gadolinium chloride group were decreased compared with saline group (P < 0.05). In pathologic histology tests, the lesion range and the extent of ischemia-reperfusion injury were all significantly increased in saline group and gadolinium chloride group. Compared with the saline group, the concentrations of interleukin-1, tumor necrosis factor-α and the apoptosis index were decreased significantly in gadolinium chloride group (P < 0.05), as well as the congestion, vacuolar degeneration and Suzuki’s score (P < 0.05). The protective effect of gdolinium chloride on ischemia-reperfusion injury of receptor’s liver might result from closing the Kupffer cells and reducing cytokine release.

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