电刺激迷走神经对脓毒症大鼠急性肺损伤的影响

Protective effects of electric stimulation of vagus nerve on acute lung injury in rat with sepsis

目的探讨电刺激迷走神经激活胆碱能抗炎通路对脓毒症大鼠急性肺损伤的影响。方法采用盲肠结扎穿孑L术（CLP）复制脓毒症大鼠模型。40只雄性SD大鼠被随机分为假手术（SHAM）组、CLP组、迷走神经切断（VGX）组和迷走神经刺激（STM）组，每组10只。CLP组行CLP；VGX组行CLP后离断双侧颈部迷走神经干；STM组在VGX组处理的基础上行左侧迷走神经干远端电刺激。所有动物于制模成功后18h经颈动脉放血处死，检测血浆肿瘤坏死因子-α（TNF-α）浓度、动脉血乳酸及血气分析；计算肺湿／干重比值；观察肺组织病理学改变及超微结构改变。结果与SHAM组比较，CLP组和VGX组血浆TNF-α浓度、动脉血乳酸值、动脉血二氧化碳分压（PaCO2）、肺湿／干重比值均升高，pH、动脉血氧分压（PaO2）以及剩余碱（BE）值均降低（P〈0．05或P〈0．01）。与CLP组比较，STM组血浆TNF—d浓度、动脉血乳酸值、PaCO2、肺湿／干重比值均降低，pH、PaO2以及BE值升高（P〈0．05或P〈0．01）。肺组织病理学和电镜下超微结构改变均显示：CLP组肺损伤较SHAM组明显加重，而STM组肺损伤较CLP组、VGX组明显减轻。结论通过电刺激迷走神经激活胆碱能抗炎通路，可起到保护脓毒症大鼠急性肺损伤的作用。

Objeetive To investigate the protective effect of stimulation of vagus nerve on acute lung injury in rat with sepsis. Methods Sepsis was reproduced by cecal ligation and puncture （CLP）. Forty male Sprague-Dawley （SD） rats were randomly divided into 4 groups （each n = 10）： SHAM group received performed sham surgery. In CLP group, CLP was performed. In vagotomy （VGX） group, rats were subjected to bilateral cervical VGX following CLP. In vagus stimulation （STM） group, rats were subjected to bilateral cervical VGX after CLP and the efferent end of the left vagus nerve was stimulated with electric current. The animals were socrificed at 18 hours after production. Tumor necrosis factor-α （TNF-α） level in blood was detected, arterial blood lactic acid concentration, pH, partial pressure of oxygen in arterial blood （PaO2）, partial pressure of carbon dioxide in arterial blood （PaCO2）, base excess （BE） and lung wet/drying （W/D） ratio were determined. The histopathology and ultra -microstructure of the lung were observed. Results The TNF-α and lactic acid concentrations, PaCO2 and W/D ratio were all increased, and pH, PaO2, BE all lowered in CLP group and VGX group compared with those of SHAM group （P〈0.05 or P〈0. 01）. Compared with CLP group, TNF-α, lactic acid concentration, PaCO2, W/D ratio in STM group were decreased obviously, and pH, PaO2 and BE were all increased （P〈0. 05 or P〈0.01）. The lung tissue pathology and ultra -microstructure changes indicated that lung injury was severe in CLP group than in SHAM group and was ameliorated in STM group compared with that of CLP group and VGX group. Conclusion The results suggest that direct electrical stimulation of the efferent end of vagus nerve can protect lung against injury induced by sepsis in rat.