中国组织工程研究

中国组织工程研究 ›› 2011, Vol. 15 ›› Issue (53): 9961-9964.doi: 10.3969/j.issn.1673-8225.2011.53.020

• 心肺移植 heart-lung transplantation • 上一篇    下一篇

p53基因转移至移植心脏的安全性

王丽平1，宋芳芳1，李祥禄1，刘  越2，贾智博3，尹新华2   

  1. 哈尔滨医科大学附属第二医院，1老年病科，3心外科，黑龙江省哈尔滨市  150086；   2哈尔滨医科大学附属第一医院心内科，黑龙江省哈尔滨市  150001
  • 收稿日期:2011-06-02 修回日期:2011-09-18 出版日期:2011-12-31 发布日期:2011-12-31
  • 通讯作者: 贾智博，副主任医师，哈尔滨医科大学附属第二医院心外科，黑龙江省哈尔滨市 150086 doctor_jiazhibo@yahoo.com.cn
  • 作者简介:王丽平☆，女，1976年生，黑龙江省肇源县人，汉族，2007年哈尔滨医科大学毕业，博士，副主任医师，主要从事心脏移植基因转移方面的研究。 wlp0502@yahoo.com.cn
  • 基金资助:

    黑龙江省教育厅2010年度科学技术研究项目(11551256)，课题名称：P53基因对心脏移植后冠状动脉内膜增生的抑制作用。

Security for adenovirus-mediated p53 gene transfer to the donor heart

Wang Li-ping1, Song Fang-fang1, Li Xiang-lu1, Liu Yue2, Jia Zhi-bo3, Yin Xin-hua2   

  1. 1Department of Geriatrics, 3Department of Cardiac Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin  150086, Heilongjiang Province, China; 2Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Harbin   150001, Heilongjiang Province, China
  • Received:2011-06-02 Revised:2011-09-18 Online:2011-12-31 Published:2011-12-31
  • Contact: Jia Zhi-bo, Associate chief physician, Department of Cardiac Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China doctor_jiazhibo@yahoo.com.cn
  • About author:Wang Li-ping☆, Doctor, Associate chief physician, Department of Geriatrics, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China wlp0502@yahoo.com.cn
  • Supported by:

    Science and Technology Research Program of Education Department of Heilongjiang Province in 2010, No. 11551256*

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被引次数

1

摘要：

背景：课题组前期实验表明野生型p53基因具有抑制移植心脏冠状动脉内膜增厚的作用。
目的：研究腺病毒介导的野生型p53基因转移至移植心脏的安全性。
方法：以Wistar大鼠为供体，SD大鼠为受体建立大鼠腹腔异位心脏移植模型，在取出供心后，经供心冠状动脉分别注射携带野生型p53基因的重组腺病毒液、携带β-半乳糖酐酶基因的重组腺病毒液和生理盐水800 µL，4 ℃静置30 min后进行心脏移植。
结果与结论：移植后 5 d，重组腺病毒液组的供心冠状动脉组织可见野生型P53蛋白的表达。移植后28 d，未见受体大鼠血液生化学指标异常和重要脏器的病理性改变，RT-PCR扩增未见腺病毒E1A区产物。说明在心脏移植中，将腺病毒介导的野生型p53基因转移至移植心脏是安全的。

关键词: 心脏移植, 腺病毒载体, 野生型p53基因, 基因转移, 安全性

Abstract:

BACKGROUND: Wild-type p53 gene transfer to the donor heart can greatly inhibit graft coronary artery intima hyperplasia and lumen narrowness.
OBJECTIVE: To study the security of adenoviral-mediated wild-type p53 gene transfer to the donor heart after heart transplantation.
METHODS: Rat models of heterotopic (abdomen) heart transplantation were developed. Wistar rats served as donors and SD rats as recipients. After donor hearts were removed, 800 µL adenoviral vector encoding the wild-type p53 gene (Ad-p53 group), adenoviral vector encoding the β-galactosidase gene (LacZ) (Ad-LacZ group) or saline (control group) were infused into the donor heart respectively before transplantation. The donor heart was stored in the 4 ℃ saline for 30 minutes before heart transplantation. At 5 days after operation, P53 protein expressions in coronary artery of donor hearts were tested by western blot analysis. At 28 days after transplantation, the serum specimen was collected for the biochemical indicators, and the major organs of the recipients were tested by the histopathological analysis and the reverse transcription polymerase chain reaction of the adenoviral E1A sequences.
RESULTS AND CONCLUSION: The expression of P53 protein was found in donor hearts in Ad-p53 group at 5 days after operation, and no expression in Ad-LacZ group and control group. At 28 days after operation, rat serum biochemistry values in three groups was normal, the major organs of the recipients were not affected seriously, no virus spread to other organs in this experimental protocol. The results confirmed that the ex vivo adenoviral-mediated gene transfer to the donor heart via the coronary artery during the heart transplantation is safe.

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