胆碱能抗炎通路对感染性休克大鼠肺的保护作用

目的:应用盲肠结扎穿孔法(CLP)建立感染性休克模型,研究胆碱能抗炎通路对感染性休克大鼠肺的保护作用。方法:采用CLP复制感染性休克模型,取成年雄性SD大鼠40只,随机分为4组。①假CLP组(Sham);②CLP组(CLP);③迷走神经切断组(VGX);④迷走神经电刺激组(STM)。各组动物均行颈总动脉置管连续监测平均动脉压。刺激方法是将左迷走神经远端连接刺激电极,于CLP术毕即刻持续电刺激(5V、2ms和1Hz)20min。分别在各组模型制备完毕或电刺激后0,1,2,4h检测血浆TNF-α含量和4h抽动脉血行血气分析、取肺组织在透射电镜下观察肺组织超微结构变化。结果:CLP组和VGX组平均动脉血压进行性下降,STM组血压下降幅度减轻,各时间点均显著高于CLP组相应的血压值。各组动物血浆TNF-α含量均在2h出现高峰,并在4h回落。STM组1h和2h与CLP组比较,血浆TNF-α含量则显著降低。4h取颈动脉血行血气分析,CLP组和VGX组血气分析pH值、PaO2和BE显著下降(P<0.01),明显低于假CLP组和STM组(P<0.05),表明CLP组和VGX组肺功能有明显损伤,STM组肺功能有明显改善。肺组织超微结构CLP组在电镜下可见肺泡Ⅱ型上皮细胞轻度增生,肺气血屏障的中间带增厚,部分线粒体膜断裂、解体、嵴粒溶解以及线粒体空泡化。STM组病理变化明显减轻。结论:电刺激迷走神经减轻肺损伤的机制与迷走神经兴奋释放大量神经递质乙酰胆碱有关。电刺激迷走神经兴奋后,其末梢释放大量乙酰胆碱,与存在于单核巨噬细胞上的乙酰胆碱受体α7亚单位结合后,阻止单核巨噬细胞TNF-α合成,从而减轻肺脏等脏器的炎性损害。电刺激迷走神经通过胆碱能抗炎通路能缓解CLP致感染性休克大鼠的进行性血压下降,降低血清TNF-α含量,减轻急性肺功能损伤和肺组织病理损害,对肺有潜在的保护作用。

Protective Effect of Electrical Stimulation of Efferent Vagus Nerve on Acute Lung Injury in Septic Shock Rats

Objective: To investigate the protective effect of electrical stimulation of efferent vagus on the acute lung injury in septic shock rats. Methods: Twenty male Sprague-Dawley rats were randomly divided into four groups: group Ⅰ(sham operation), group Ⅱ (cecal ligation and puncture,and bilateral cervical vagus nerve isolation), group Ⅲ (bilateral cervical vagotomy following cecal ligation and puncture, CLP) and group Ⅳ (bilateral cervical vagotomy after cecal ligation and puncture and the distal end of left vagus nerve trunk was stimulated by a stimulation module with constant voltage (5 V, 2 ms, 1 Hz) for 20 min immediately after the models were operated). Before stimulation, a blood pressure transducer were implanted into the common carotid artery for continuous registration of mean arterial blood pressure (MAP). Blood samples of these rats were collected at 0, 1, 2 and 4 h after stimulation and lung samples were collected at 4 h in all groups. Serum TNF-α was determined. Results: The MAP gradully decreased, the function of lung was reduced and amount of serum TNF-α significantly increased after cecal ligation and puncture(P<0.01). Electrical stimulation of the efferent vagus nerve significantly increased the MAP and attenuate serum TNF-α amounts and alleviate the injury and inflammation in lung tissue. Conclusion: Direct electrial stimulation of the peripheral vagus nerve can significantly attenuated peak serum TNF-α levels and alleviated the injury and inflammatory response in the lung tissue, thus it might produce a potential protective effect on acute lung injury during septic shock in rats.