迷走神经刺激激活胆碱能抗炎通路对犬心肌缺血/再灌注损伤的保护作用  

Protective effect of vagus nerve stimulation on myocardial ischemia/reperfusion injury via activation of cholinergic anti-inflammatory pathway in canines

作　　者：穆合代斯.阿不拉 娜几娜.吾格提 王坤[2] 艾力曼.马合木提 

机构地区：[1]新疆医科大学第一附属医院急诊内科,乌鲁木齐830011 [2]新疆医科大学第一附属医院心力衰竭科,乌鲁木齐830011

出　　处：《岭南心血管病杂志》2015年第4期560-565,572,共7页South China Journal of Cardiovascular Diseases

摘　　要：目的探讨电刺激单侧迷走神经激活胆碱能抗炎通路对犬心肌缺血/再灌注损伤的影响。方法 18只成年杂种犬按随机数字表法随机分为3组(n=6):假手术组(sham组);缺血/再灌注组(I/R组);右侧迷走神经干刺激+缺血/再灌注组(STM组)。测定各组血流动力学指标,于再灌注2 h后经颈内静脉采血,采用酶联免疫吸附试验(ELISA)法检测血清乙酰胆碱(acetylcholine,Ach)、肿瘤坏死因子-α(tumor necrosis factor alpha,TNF-α)和白细胞介素-6(interleukin-6,IL-6)的浓度。免疫组化法测定α7亚基烟碱型Ach受体(α7n ACh R)的表达水平。苏木素伊红染色观察中性粒细胞浸润程度。结果缺血后再灌注120 min后,与sham组比较,I/R组血清TNF-α和IL-6浓度均显著下降,Ach浓度升高,α7n Ach R蛋白表达显著减少,差异有统计学意义(P<0.05);STM组血清Ach、TNF-α、IL-6浓度和α7n Ach R蛋白表达量与sham组比较,差异无统计学意义(P>0.05)。与I/R组比较,STM组血清Ach浓度和α7n Ach R蛋白表达量显著增加,血清TNF-α和IL-6浓度降低,差异有统计学意义(P<0.05)。与基线水平比较,缺血后再灌注120 min后I/R组血清TNF-α和IL-6浓度明显增加,Ach浓度下降,差异有统计学意义(P<0.05);sham组和STM组血清Ach、TNF-α和IL-6浓度未见明显改变,差异无统计学意义(P>0.05)。I/R组血清TNF-α、IL-6浓度分别与Ach呈负相关(P<0.05);STM组血清TNF-α、IL-6浓度分别与Ach呈负相关(P<0.05)。I/R组可见大量中性粒细胞浸润心肌组织,STM组可见少量中性粒细胞浸润。结论刺激右侧迷走神经干可通过激活迷走神经的胆碱能抗炎通路,抑制全身和局部的炎症反应从而减轻犬心肌缺血/再灌注损伤。Objectives To investigate the effect of cholinergic anti-inflammatory pathway with vagus nerve stimulation on ischemia / reperfusion（I / R） injury in canines. Methods A number of 18 adult mongrel dogs were randomly divided into 3 groups（n=6 each）： sham operation group（sham group）, I / R group and right vagus nerve stimulation ＋I / R group（STM group）. Hemodynamic indexes were measured. Two hours after reperfusion, internal jugular venous blood was collected. Serum concentrations of acetylcholine（Ach）, tumor necrosis factor alpha（TNF-α） and interleukin-6（IL-6） were detected by enzyme-linked immunosorbent assay（ELISA）. Concentration of alpha-7 nicotinic acetylcholine receptor（α7n ACh R） was detected with immuno-histochemical method. Hematoxylin and eosin staining was used to observe the degrees of neutrophil infiltration. Results Two hours after reperfusion, compared with those in sham group, serum concentrations of TNF- α and IL-6 significantly decreased, serum concentration of Ach increased and protein expression of α7n ACh R significantly reduced in I / R group（P〈0.05）. Protein expression of α7n ACh R,serum concentrations of Ach, TNF-α and IL-6 had no significant difference between STM group and sham group（P〈0.05）. Compared with those in I / R group, serum concentration of Ach and protein expression of α7n ACh R significantly increased, and serum concentrations of TNF-α and IL-6 decreased in STM group（P〈0.05）. Compared with the baseline data, serum concentrations of TNF-α and IL-6 significantly increased and serum concentration of Ach decreased in I / R group two hours after reperfusion（P〈0.05）, while serum concentrations of Ach, TNF- α and IL-6had no significant changes in sham group and STM group（P〈0.05）. TNF-α and IL-6 were negatively correlated with Ach in I / R group and STM group（P〈0.05）. A massive infiltration of neutrophils was detected in myocardial tissues of I / R group, and a small amount of infiltration of neutroph

关 键 词：心肌缺血/再灌注损伤 胆碱能抗炎通路 迷走神经干 乙酰胆碱 

分 类 号：R542.2[医药卫生—心血管疾病]