Effects of transection of cervical spinal cord on lipopolysaccharide induced acute lung injury in rat

目的 研究颈脊髓切断对内毒素血症大鼠急性肺损伤的影响及可能机制.方法 72只SD大鼠随机分为3组:正常对照组(NC组,8只),内毒素血症组(ET组,32只)及内毒素血症+颈脊髓切断组(TCSC组,32只),后两组按不同时间点(3、6、12和48 h)又分为4个亚组,每个亚组8只.静脉注射脂多糖(LPS)10 mg/kg制备内毒素血症模型.TCSC组注射LPS前切断大鼠颈7脊髓.在不同时间点采血,并留取肺组织.采用高效液相色谱仪-电化学检测法和酶联免疫吸附法(ELISA)分别测定血浆去甲肾上腺素(NE)和白细胞介素-6(IL-6)的浓度;用血气分析仪检测动脉血氧分压(PaO2);观察各组大鼠肺组织病理学改变及肺湿/干重(W/D)比值.结果 TCSC组6、12和48 h血浆NE浓度、肺W/D比值较ET组均显著降低,PaO2较ET组显著升高,差异均有统计学意义(P均<0.05);TCSC组肺损伤程度减轻;3、6、12和48 h血浆IL-6均明显低于ET组(P均<0.05).相关性分析显示,血浆NE与IL-6浓度呈显著正相关(r=0.458,P<0.05),与PaO2呈显著负相关(r=0.528,P<0.05).结论 切断大鼠颈脊髓后造成去交感神经支配可能通过抑制肾上腺素能受体的过度激活而减轻内毒素血症大鼠急性肺损伤的程度,继而改善肺的氧合.Objective To investigate the effects of transection of cervical spinal cord (TCSC) on acute lung injury (ALI) and its potential mechanism in rat. Methods Seventy-two rats were randomly divided into three groups: normal control group (NC, n=8), endotoxemia group (ET, n=32) and endotoxemia with TCSC group (TCSC, n=32), and the latter two groups were divided into four subgroups respectively according to different time intervals (n=8). Endotoxemia model was established by injecting lipopolysaccharide (LPS, 10 mg/kg) intravenously, and the spinal cord at 7th cervical spine of rats was transected in TCSC group. Samples of blood and lung were collected at different time intervals. The plasma levels of norepinephrine (NE) and interleukin-6 (IL-6) were measured by high performance liquid chromatography (HPLC) and enzyme-lined immunosorbent assay (ELISA) respectively, and arterial blood oxygen pressure (PaO2) was determined by blood-gas analyser. The changes in histopathology and lung wet/dry weight (W/D) ratio were also observed in every group. Results The changes in the levels of NE and lung W/D ratio of the TCSC group was significantly decreased than those of ET group, but PaO2 of TCSC group was increased obviously than that of ET group (all P<0.05), and the degree of lung injury was less intensive in the TCSC group. At all the time points, the level of IL-6 of TCSC group was lower compared with ET group (all P<0.05). The results of correlation analysis suggested that there was a positive correlation between plasma NE and IL-6 concentration (r=0.458, P<0.05), a negative correlation between NE and PaO2 (r=0.528, P<0.05). Conclusion Sympathectomy as a result of TCSC at 7th cervcal spine may palliate the degree of ALI and improve oxygenation in rats with endotoxemia by inhibiting excessive activation of adrenoceptor.北京市自然科学基金; 北京市教委科技发展计划项目PubMed中文核心期刊要目总览(PKU)中国科技核心期刊(ISTIC)中国科学引文数据库(CSCD)010621-624,插32