Clinical Effects of "Selective Drug" Regulating Vagus Nerve Signal Pathway in Vagally-Mediated Atrial Fibrillation.

Clinical Effects of "Selective Drug" Regulating Vagus Nerve Signal Pathway in Vagally-Mediated Atrial Fibrillation.
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DOI:
10.12659/msm.906044
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发表时间:
2018-04-13
期刊:
Medical science monitor : international medical journal of experimental and clinical research
影响因子:
--
通讯作者:
Zhou X
Zhou X
中科院分区:
其他
文献类型:
--
作者:
Lou X;Lu Y;Tang B;Zhou X

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心脏自主神经系统通过G蛋白信号转导通路在心房颤动(AF)的发生和发展中发挥着至关重要的作用。因此,干预G蛋白信号转导通路可能是调节自主神经活动预防迷走神经介导房颤的新“选择性药物”方法。 17只成年比格犬随机分为3组:羞耻手术对照组(A组,n=5)、空载体基因对照组(B组,n=6)、Gαi2ctp基因实验组(C组,n=6)。 A组动物前房壁注射生理盐水,B组和C组动物同一区域注射空载体或Gαi2ctp载体的重组腺病毒。 B组和C组采用快速心房起搏方法诱发房颤。为了确定迷走神经调节的临床效果,通过电生理学研究评估有效不应期(ERP)和场动作电位持续时间(FAPD)。免疫组化法检测不同部位酪氨酸羟化酶(TH)和胆碱乙酰转移酶(CHAT)的表达水平。 Gαi2ctp基因转染成功后,B组ERP、FAPD显着降低(P<0.05),TH、CHAT表达显着升高(P<0.05),而A、C组差异无统计学意义(P>0.05)。重组腺病毒介导的犬心肌细胞中Gαi2ctp的过度表达可以干扰迷走神经的活动,逆转电重构的发生和进展,降低房颤的发生率。
The cardiac autonomic nervous system plays a crucial role in genesis and development of atrial fibrillation (AF) through the G protein signal transduction pathway. Therefore, intervening in the G protein signal transduction pathway may be a new “selective drug” method to regulate autonomic nerve activity to prevent vagally-mediated AF. Seventeen adult beagles were randomized into 3 groups: shame-operation control group (group A, n=5), empty vector gene control group (group B, n=6), and Gαi2ctp gene experimental group (group C, n=6). Group A was injected with normal saline into the anterior atrial wall, and group B and group C animals were injected with recombinant adenovirus with empty vector or Gαi2ctp vector in the same region. AF was induced by the method of rapid atrial pacing in groups B and C. To determine the clinical effect of vagal modulation, the effective refractory periods (ERP) and field action potential duration (FAPD) were evaluated by electrophysiological study. The expression levels of tyrosine hydroxylase (TH) and choline acetyl transferase (CHAT) in different parts were determined with immunohistochemistry. After successful Gαi2ctp gene transfer, in group B, the ERP and FAPD significantly decreased (P<0.05), and TH and CHAT expression observably increased (P<0.05), while those differences were absent between groups A and C (P>0.05). Recombinant adenovirus-mediated overexpression of Gαi2ctp in canine myocardial cells can interfere with the activity of the vagus nerve, reverse the development and progression of electrical remodeling, and reduce the incidence of AF.
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