脑肠肽Ghrelin通过迷走神经对呼吸机相关性肺损伤大鼠发挥保护作用

Protective effect of Ghrelin on ventilator induced lung injury through vagus nerve in rats

目的研究Ghrelin是否通过迷走神经对呼吸机相关性肺损伤大鼠发挥保护作用。方法采用随机数字法,将48只健康雄性SD大鼠分为6组（8只/组）：常规机械通气组（LV组,潮气量=8ml/kg）,大潮气量机械通气组（VILI组,潮气量=30ml/kg）,Ghrelin＋大潮气量机械通气组（GH＋VILI组）,迷走神经切除＋大潮气量机械通气组（Vag＋VILI组）,迷走神经假切除＋大潮气量机械通气组（Sham＋VILI组）,Ghrelin＋迷走神经切除＋大潮气量机械通气组（GH＋Vag＋VILI组）。其中迷走神经切除各组于机械通气前1h行右侧迷走神经干切除,注射Ghrelin各组于机械通气前30min腹腔注射Ghrelin（10nmol）,VILI组注射等量生理盐水。各组行机械通气4h,期间每小时监测心率、平均动脉压、氧合指数和肺弹性阻力。实验结束后处死大鼠取肺组织,计算肺湿/干重（W/D）比值和髓过氧化物酶（MPO）活性,采用酶联免疫吸附法测定支气管肺泡灌洗液（BALF）中肿瘤坏死因子α（TNF-α）和白介素8（IL-8）含量。结果机械通气期间,各组大鼠平均动脉压稳定,未见明显差异。与LV组相比,VILI组各时间点氧合指数明显降低,肺弹性阻力明显增加（P值均〈0.05）,肺W/D比值、MPO水平、BALF中炎性因子TNF-α及IL-8水平明显升高（P值均〈0.05）。与VILI组相比,GH＋VILI组各时间点氧合指数明显升高,肺弹性阻力显著降低（P值均〈0.05）,肺W/D比值、MPO水平、BALF中炎性因子TNF-α及IL-8水平明显降低（P值均〈0.05）。与VILI组相比,GH＋Vag＋VILI组氧合指数、肺弹性阻力、肺W/D比值、MPO水平、BALF中炎性因子TNF-α及IL-8水平均未见明显差异。结论Ghrelin是通过激活迷走神经而对呼吸机相关性肺损伤发挥保护作用的。

Objective To investigate whether Ghrelin protects against ventilator induced lung injury through vagus nerve in rats. Methods 48 healthy male SD rats were randomly divided into six groups （eight in each group） ：conventional mechanical ventilation group （I.V group, tidal volume= 8 ml/kg）, high tidal volume ventilation group （VILI group, tidal volume = 30 ml/kg）, Ghrelin ＋ high tidal volume ventilation group （GH ＋ VILI group）, vagotomy ＋ high tidal volume ventilation group （ Vag ＋ VILI group）, sham vagotomy ＋ high tidal volume ventilation group （Sham＋ VILI group）, Ghrelin＋ vagotomy＋ high tidal volume ventilation group （GH＋Vag＋VILI group）. Right vagotomy was performed at 1 h before ventilation in each vagotomy group. Ghrelin （10 nmol） was injected intraperitoneally at 30 rain before mechanical ventilation in each Ghrelin group, and VILI group was injected with normal volume saline. Each group took mechanical ventilation for four hours and heart rate, mean arterial pressure, oxygenation index, lung elastic resistance were examined hourly. At the end of the experiment, the rats were executed to take lung tissue, lung wet/dry weight ratio （W/D） and myeloperoxidase （MPO） activity were examined, the levels of tumor necrosis factor-α （TNF-α） and interleukin-8 （IL-8） in bronchoalveolar lavage fluid （BALF） were measured by enzyme linked immunosorbent assay. Results During the mechanical ventilation, the mean arterial pressure in each group was stable and there was no statistical difference. Compared with the LV group, the oxygenation indexe in VILI group was decreased obviously and lung elastic resistance was significantly increased at each time point （all P 〈0.05）, lung W/D ratio, MPO level, the levels of inflammatory factors TNF-α and IL-8 in BALF were increased significantly （all P 〈0.05）. Compared with the VILI group, the oxygenation index in GH q-VILI group was significantly higher and lung elastic resistance was significantly decreased at each time point （all P 〈 0.05）, lung W/D ratio, MPO level, the levels of inflammatory factors TNF-α and IL-8 in BALF were decreased significantly （all P 〈0.05）. There was no statistical difference in the oxygenation index, lung elastic resistance, lung W/D ratio, MPO level and the levels of inflammatory factors TNF-α and IL-8 in BALF between VILI group and GH＋Vag＋VILI group. Conclusions Ghrelin palys protective roles in ventilator induced lung injury by activating the vagus nerve.