低强度迷走神经刺激对阻塞性睡眠呼吸暂停诱发犬心房颤动的影响

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摘要目的探讨低强度迷走神经刺激（LL-VNS）干预阻塞性睡眠呼吸暂停（OSA）诱发犬心房颤动的机制。方法 18只成年健康雄性比格犬随机分为3组：对照组（n=6）、OSA组（n=6）和OSA+LL-VNS组（n=6）。将各组犬在全身麻醉状态下进行气管插管，OSA组和OSA+LL-VNS组模拟OSA过程，即憋气2 min，通气8 min，每10分钟为1个循环，持续6 h；OSA+LL-VNS组从第3 h至实验结束给予LL-VNS；对照组不憋气。分别检测3组动物建模0、1、3、6 h的血气指标以及建模0、3、6 h的炎症指标肿瘤坏死因子-α（TNF-α）、白细胞介素-2（IL-2）和白细胞介素-6（IL-6）的变化。全程记录犬的动脉血压。实验结束后取心房肌组织用于做苏木精-伊红（HE）染色。结果成功建立了OSA模型。憋气前后OSA组和OSA+LL-VNS组收缩压均有显著变化（P < 0.05），两组间收缩压比较差异无统计学意义（P > 0.05）。OSA组炎症指标TNF-α、IL-2在6 h处较对照组明显升高，OSA+LL-VNS组较OSA组明显降低，差异均有统计学意义（P < 0.05）。各个时间段，IL-6未表现出明显差异（P > 0.05），OSA组的心房有效不应期（ERP）逐渐缩短，心房颤动（AF）持续时间逐渐延长（P < 0.05）。在OSA+LL-VNS组建模0~3 h，心房ERP是逐渐缩短的，AF持续时间是逐渐延长的（P < 0.05）；在3~6 h给予LL-VNS后与前3 h相比，心房ERP又会逐渐延长，AF持续时间逐渐缩短（P < 0.05）。OSA组与对照组相比心房肌组织的HE染色切片显示心房肌细胞排列紊乱，细胞裂隙增宽，经LL-VNS干预以后上述改变在一定程度上得到了逆转。结论炎性因子与AF的发生和发展存一定的正相关，同时LL-VNS能够降低OSA对AF的诱发率。因此，降低机体炎性反应可能是LL-VNS减少AF诱发率的机制之一。

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	孟庆军张玲贾索尔·肖克热提王雪生周贤惠汤宝鹏▲

关键词 ：低强度迷走神经刺激, 心房颤动, 阻塞性睡眠呼吸暂停, 炎性因子

Abstract：Objective To investigate the mechanism of low-level vagus nerve stimulation (LL-VNS) in the treatment of atrial fibrillation (AF) induced by obstructive sleep apnea (OSA) in dogs. Methods Eighteen adult male healthy beagle dogs were randomly divided into three groups:control group (n = 6),OSA group (n = 6) and OSA + LL-VNS group (n = 6). All animals were intubated under general anesthesia. Both the OSA group and the LL-VNS group performed the same OSA process,which was suffocated for 2 min, ventilated for 8 min, and 10 min was a cycle lasting 6 h. The OSA + LL-VNS group was given LL-VNS from the third hour to the end of the experiment and the control group was not suffocated. The changes of blood gas indexes at 0, 1, 3 h, and 6 h, and inflammatory markers including tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2) and interleukin-6 (IL-6) at 0, 3 h and 6 h after modeling were detected. The canine arterial blood pressure was recorded throughout the whole experiment. At the end of the experiment, the atrial muscle tissue was taken for hematoxylin-eosin (HE) staining. Results OSA model was successfully established (P < 0.05). The systolic blood pressure of OSA group and OSA + LL-VNS group had significantly changed before and after OSA (P < 0.05), but there was no significant difference between the two groups (P > 0.05). Inflammation indicators-TNF-α, IL-2 at 6 hours in OSA group were significantly higher than the control group, but in OSA + LL-VNS group, it was significantly lower than the control group, the differences were statistically significant (P < 0.05). IL-6 showed no significant change in each time period (P > 0.05). In OSA group the atrial relative refractory period (ERP) was gradually shortened, and AF duration was gradually prolonged (P < 0.05). In OSA + LL-VNS group, from 0 h to 3 h the atrial ERP was gradually shortened and the duration of AF was gradually prolonged (P < 0.05); from 3 h to 6 h after given LL-VNS, the atrial ERP was gradually extended and AF duration reduced compared with 0 h to 3 h (P < 0.05). Compared with the control group, the HE slices of the atrial muscle in the OSA group showed that the atrial myocytes were disordered and the cell gap widened and After LL-VNS intervention, the above changes were reversed to some extent. Conclusion Inflammatory factors are positively correlated with the genesis and development of AF, and LL-VNS can reduce the incidence of AF. Therefore, reducing the body's inflammatory response may be one of the mechanisms by which LL-VNS reduces AF inducibility.

Key words： Low-level vagus nerve stimulation Atrial fibrillation Obstructive sleep apnea Inflammatory factors

基金资助:国家自然科学基金资助项目（81560064）。

通讯作者: ▲通讯作者

作者简介: 孟庆军（1988.10-），男，新疆医科大学2015级内科学（心血管病学）专业在读硕士研究生；研究方向：心脏起搏与心电生理。

引用本文:

孟庆军张玲贾索尔·肖克热提王雪生周贤惠汤宝鹏▲. 低强度迷走神经刺激对阻塞性睡眠呼吸暂停诱发犬心房颤动的影响[J]. 中国医药导报, 2018, 15(5): 4-8.
MENG Qingjun ZHANG Ling Jiasuoer·Xiaokereti WANG Xuesheng ZHOU Xianhui TANG Baopeng▲. Effect of low-level vagus nerve stimulation on atrialfibrillation induced by obstructive sleep apnea in dogs. 中国医药导报, 2018, 15(5): 4-8.

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