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重组腺病毒Ad-hBNP对慢性心力衰竭大鼠心肌细胞凋亡因子及Ⅰ、Ⅲ型胶原表达的影响

宋衍秋1,赵莉莉。2,毛用敏1,赵鸿铭1,崔让庄1   

  1. 1. 天津市胸科医院
    2. 天津市胸科医院心研所
  • 收稿日期:2012-01-06 修回日期:2012-08-29 出版日期:2013-01-15 发布日期:2013-01-15
  • 通讯作者: 毛用敏

The expression of apoptotic factors and collagen type I & III by recombinant adenovirus Ad-hBNP in rats’ hearts with chronic heart failure

  • Received:2012-01-06 Revised:2012-08-29 Published:2013-01-15 Online:2013-01-15

摘要:

【摘要】 目的观察外源基因人B型利钠肽对慢性心力衰竭大鼠心肌细胞凋亡因子及Ⅰ、Ⅲ型胶原表达的影响。方法 30只慢性心力衰竭模型大鼠,随机分为携带人B型利钠肽基因重组腺病毒组(Ad-hBNP组,14只)、重组空白腺病毒组(Ad-Track组,8只)、生理盐水组(NS组,8只),分别给予腹腔注射人B型利钠肽基因重组腺病毒、重组空白腺病毒及生理盐水1mL,每周1次,共4周。另设10只未造模但实行了假手术的大鼠为假手术组;4周后处死大鼠,行RT-PCR检测心肌组织Bcl-2、Bax、Caspase-3及Ⅰ、Ⅲ型胶原mRNA含量。结果 Ad-hBNP治疗后,Ad-hBNP组大鼠心肌组织Bcl-2mRNA表达较Ad-Track组及NS组升高;BaxmRNA表达较假手术组升高;Caspase-3mRNA表达较Ad-Track组、NS组及假手术组均升高。Ad-hBNP组Ⅰ、Ⅲ型胶原mRNA表达较Ad-Track组降低。结论间断给予Ad-hBNP能够影响慢性心力衰竭大鼠心肌细胞凋亡相关基因的表达,减少心肌细胞间质Ⅰ、Ⅲ型胶原的表达。 

关键词: 利钠肽, 脑, 心力衰竭, 充血性, 细胞凋亡, 基因疗法

Abstract: Objective: To observe the expression of apoptotic factors and collagen type I & III by recombinant adenovirus Ad-hBNP in rats’ hearts with chronic heart failure. Methods: Thirty CHF rats defined by echocardiography at 12 weeks post abdominal aortic constriction were randomly divided into Ad-hBNP group (2.5×1010 VP/mlNS Ad-hBNP 1 ml/weekx4, n=14), Ad-Track group (n=8), placebo group (NS, n=8), 10 sham-operated rats served as control group. After 4 weeks treatment, the mRNA expression of Bcl-2, Bax, Caspase-3 and collagen type I & III were detected by RT-PCR. Results: The mRNA expression of Bcl-2 and Caspase-3 were significantly decreased in the Ad-hBNP group [2.70±1.86, 0.75±0.30] than those in the Ad-Track group[(0. 49±0.02, P<0.01), (0.43±0.26, P<0.05)] and in the NS group [(0.95±0.17, P<0.05), (0.37±0.16, P<0.05)]. The mRNA expression of Bax in the Ad-hBNP group [0.86±0.17] was significantly increased than the sham group [0.70±0.07,P<0.05], but was decreased than the Ad-Track group and the NS group. The mRNA expression of collagen type I & III were also decreased in the Ad-hBNP group than the the Ad-hBNP group. Conclusion:Exogenous hBNP affected the mRNA expression of apoptosis factors in the rats’ hearts with chronic heart failure , also reduced the mRNA expression of collagen type I & III, and maybe attenuated remodeling in CHF rats.

Key words: Natriuretic peptide, brain, Heart failure, congestive, Apoptosis, Gene therapy