外源hTERT基因转染对老年大鼠供肝缺血再灌注损伤的防护作用

山东大学学报(医学版) ›› 2013, Vol. 51 ›› Issue (8): 13-16.

外源hTERT基因转染对老年大鼠供肝缺血再灌注损伤的防护作用

靳斌1，王伟2，刘泽阳1，李广振1，杜刚1，张宗利1，韩立涛1，黄国振1，唐振宇1

1.山东大学齐鲁医院普外科； 2.山东大学医学院生物化学与分子生物学研究所，济南 250012

收稿日期:2013-01-24 出版日期:2013-08-10 发布日期:2013-08-10
通讯作者: 靳斌， E-mail：jinbin9449@yahoo.com.cn
基金资助:
山东省优秀中青年科学家科研奖励基金(2009BSB02216)

Protection against ischemiareperfusion injury in aged liver donor by induction of exogenous hTERT gene

JIN Bin1, WANG Wei2, LIU Ze-yang1, LI Guang-zhen1, DU Gang1, ZHANG Zong-li1, HAN Li-tao1, HUANG Guo-zhen1, TANG Zhen-yu1

1. Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, China;
2. Institute of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan 250012, China

Received:2013-01-24 Online:2013-08-10 Published:2013-08-10

摘要/Abstract

摘要：

目的研究老年大鼠与成年大鼠肝脏缺血再灌注损伤的程度；在肝移植前将外源端粒酶逆转录酶(TERT)基因导入老年大鼠供肝内，移植成功后观察该基因对老年大鼠供肝缺血再灌注损伤的影响。方法 Wistar大鼠共分为2组：Ⅰ组为成年大鼠(5个月)，Ⅱ组为老年大鼠(16~18个月)。移植成功后，检测ALT、维生素C和维生素E含量，超氧化物歧化酶(SOD)、过氧化氢酶(CAT)及丙二醛(MDA)含量，比较两组缺血再灌注损伤程度；另取老年大鼠分3组：A组(基因干预组)，将腺病毒介导的外源hTERT基因(rAdTERT)导入老年供肝；B组(空载体病毒组)；C组(生理盐水组)。干预后不同时间检测各项指标来分析外源hTERT基因对减轻老年大鼠肝移植模型供肝缺血再灌注损伤的作用。结果老年组大鼠的维生素C、维生素E、SOD、CAT的含量低于成年组大鼠(P＜0.05)；老年组大鼠MDA和ALT含量高于成年组大鼠(P＜0.05)。与空载体病毒组和生理盐水组相比，hTERT基因干预组的凋亡指数明显降低，ALT明显降低(P<0.05)，端粒酶活性明显提高，且基因干预组肝组织仅存在轻度的细胞损伤。结论老年大鼠肝脏的缺血再灌注损伤较成年大鼠重；导入外源hTERT基因能减轻老年大鼠供肝缺血再灌注损伤。

关键词: hTERT基因；缺血再灌注损伤；肝移植；老年大鼠

Abstract:

Objective To investigate the liver ischemiareperfusion (I/R) injury of adult and aged rats. Exogenous human telomerase reverse transcriptase (hTERT) gene was transferred into aged rats′ liver before liver transplantation, and then the effects of the gene on cell apoptosis caused by I/R injury were observed. Methods Wistar rats were divided into two groups, with adult rats (5 months) in group Ⅰ and aged rats (16~18 months) in group Ⅱ. After transplantation, ALT content, chronic oxidative stress, lipid peroxidation related indicators including vitamin C and vitamin E, the content of superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) were tested. The aged rats were divided into 3 groups: group A were pretreated with exogenous hTERT gene, group B with adenovirus vector and group C with physiologic saline. The indicators were detected to analyze the effects of exogenous hTERT gene on I/R injury. Results Contents of vitamin C, vitamin E, SOD, CAT were lower in group Ⅱ than in group Ⅰ (P<0.05); MDA and ALT were higher in group Ⅱ than in group Ⅰ (P<0.05). The apoptotic index and ALT level were significantly lower in group A than in group B and C (P＜0.05), while telomerase activity was increased and histological injury was milder in group A. Conclusion Compared with that in the adult rats, the I/R injury in aged liver donors were severer. Exogenous hTERT gene induction offers protection against I/R injury in aged liver.

Key words: hTERT gene; Ischemiareperfusion injury; Liver transplantation; Aged rat

中图分类号:

R657.3

靳斌1，王伟2，刘泽阳1，李广振1，杜刚1，张宗利1，韩立涛1，黄国振1，唐振宇1. 外源hTERT基因转染对老年大鼠供肝缺血再灌注损伤的防护作用[J]. 山东大学学报(医学版), 2013, 51(8): 13-16.

JIN Bin1, WANG Wei2, LIU Ze-yang1, LI Guang-zhen1, DU Gang1, ZHANG Zong-li1, HAN Li-tao1, HUANG Guo-zhen1, TANG Zhen-yu1. Protection against ischemiareperfusion injury in aged liver donor by induction of exogenous hTERT gene[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2013, 51(8): 13-16.

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