中国组织工程研究

中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (44): 8171-8174.doi: 10.3969/j.issn.1673-8225.2010.44.001

• 心肺移植 heart-lung transplantation •    下一篇

p53基因对移植心脏冠状动脉内膜增厚的抑制

王丽平1，刘  越2，贾智博3，李  颖1，张一娜1，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
  • 出版日期:2010-10-29 发布日期:2010-10-29
  • 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，黑龙江哈尔滨 150086 doctor_jiazhibo@yahoo.com.cn
  • 作者简介:王丽平☆，女，1976年出生，黑龙江省肇源县人，汉族，2007年哈尔滨医科大学毕业，博士，主治医师，主要从事心脏移植基因转移研究。 wlp0502@yahoo.com.cn
  • 基金资助:

    哈医大二院博士科研基金项目(BS2008-25)，课题名称：野生型p53基因对心脏移植后冠状动脉病的抑制作用研究；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。

Inhibition effect of p53 gene on coronary artery intima hyperplasia following heart transplantation

Wang Li-ping1, Liu Yue2, Jia Zhi-bo3, Li Ying1, Zhang Yi-na1, Yin Xin-hua2   

  1. 1 Department of Senile Disease, 3 Department of Cardiac Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin  150086, Heilongjiang Province, China; 2 Department of Cardiology, the First Affiliated Hospital of Harbin Medical University, Harbin  150001, Heilongjiang Province, China
  • Online:2010-10-29 Published:2010-10-29
  • Contact: Jia Zhi-bo, Associate chief physician, Department of Cardiology, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China
  • About author:Wang Li-ping☆, Doctor, Attending physician, Department of Senile Disease, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China wlp0502@yahoo.com.cn
  • Supported by:

    the Scientific Research Foundation for Doctors of the Second Affiliated Hospital of Harbin Medical University, No. BS2008-25*; the Science and Technology Research Foundation of Education Department of Heilongjiang Province in 2010, No.11551256*

PDF

457

被引次数

7

摘要：

背景：研究表明野生型p53基因具有抑制血管平滑肌细胞增殖、减轻血管内膜损伤后内膜增生和管腔狭窄的作用。
目的：观察野生型p53基因对心脏移植后移植心脏冠状动脉内膜增厚的抑制作用。
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，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(Ad-p53组)、携带β-半乳糖酐酶基因的重组腺病毒液(Ad-LacZ组)和生理盐水(对照组) 800 µL，4 ℃静置30 min后进行心脏移植。移植后5 d，采用RT-PCR扩增法检测各组供心冠状动脉组织外源性p53表达；移植后28 d，组织学观察移植心脏，计算各组冠状动脉内膜与中膜厚度比和血管壁厚度与管腔直径比。
结果与结论：移植后5 d，Ad-p53组供心内可见野生型p53基因的表达。移植后28 d，Ad-p53基因组冠状动脉内膜与中膜厚度比和血管壁厚度与管腔直径比均较Ad-LacZ组及对照组明显减小(P < 0.05)，Ad-LacZ组和对照组比较差异无显著性意义(P > 0.05)。结果证实在心脏移植中，采用冠状动脉注射法可以将目的基因转移至供心内，供心内转染野生型p53基因能显著抑制移植心脏冠状动脉内膜增生，减轻管腔狭窄程度。

关键词: 心脏移植, 基因转移, 冠脉内膜增厚, 野生型p53基因, 器官移植

Abstract:

BACKGROUND: Wild-type p53 gene can inhibit vascular smooth muscle cells proliferation, relieve graft coronary artery vascular intima hyperplasia and lumina narrow after vascular intima injury. 
OBJECTIVE: To evaluate the inhibition effect of wild-type p53 gene transfer on graft coronary artery intima hyperplasia after heart transplantation.
METHODS: Rat model of heterotopic (abdomen) heart transplantation was 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. p53 gene mRNA expressions in coronary artery of donor hearts were tested by reverse transcription PCR at 5 days after operation. At 28 days after transplantation, the donor hearts and coronary artery were observed under a microscope, and the ratio of intima/media thickness and vessel wall thickness/lumina diameter was calculated. 
RESULTS AND CONCLUSION: The expression of p53 gene was found in donor hearts in Ad-p53 group at 5 days after operation. At 28 days after operation, the ratio of intima/media thickness and vessel wall thickness/lumina diameter were lower in Ad-p53 group than in Ad-LacZ and control group (P < 0.05). Ad-LacZ and control group show no significant difference (P > 0.05). The results confirmed that it is feasible to transfer target gene to the donor heart by intracoronarily injection. Wild-type P53 gene transfer to the donor heart can inhibit graft coronary artery intima hyperplasia and lumens narrow significantly.

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