迷走神经刺激对脓毒症相关性脑病大鼠的保护作用  

Protective effects of vagus nerve stimulation on rats with sepsis-associated encephalopathy

作　　者：李娜[1] 李志峰[1] 项辉[1] 王翔[1] 张雪艳[1] 李建国[1] 

机构地区：[1]武汉大学中南医院重症医学科,湖北武汉430071

出　　处：《中华危重病急救医学》2015年第6期509-513,共5页Chinese Critical Care Medicine

基　　金：国家自然科学基金（30972852）

摘　　要：目的：观察电刺激迷走神经对脓毒症相关性脑病的影响，并探讨其可能的作用机制。方法将40只成年雄性SD大鼠按随机数字表法分为假手术组、模型组、迷走神经切断组（VGX组）、迷走神经刺激组（VNS组），每组10只。经股静脉注射脂多糖（LPS）10 mg/kg制备脓毒症大鼠模型，假手术组给予等量生理盐水；VGX组制模前30 min行左颈部迷走神经切除术，VNS组制模后30 min开始刺激左颈部迷走神经。假手术组行脑电图检查后处死大鼠并留取标本，其他3组于制模后2、4和6h监测脑电图改变，计算δ波百分比；制模后6 h经腹主动脉取血后处死大鼠取脑组织，采用酶联免疫吸附试验（ELISA）检测血浆和脑组织中TNF-α含量；光镜和透射电镜下观察大鼠前额叶皮质组织病理学和超微结构改变。结果与假手术组比较，模型组制模后2、4和6 h脑电图δ波百分比明显增加〔（14.52±0.50）%、（16.70±0.85）%、（17.35±0.36）%比（12.60±0.46）%，均P＜0.01〕，可判断脓毒症大鼠发生了早期脑功能障碍。与模型组比较，VNS组制模后2、4、6 h脑电图δ波百分比均明显减少〔（13.10±0.24）%比（14.52±0.50）%，（12.81±0.53）%比（16.70±0.85）%，（12.62±0.37）%比（17.35±0.36）%，均P＜0.01〕；而VGX组无此作用。与假手术组比较，模型组血浆和脑组织TNF-α含量均明显增高〔血浆TNF-α（ng/L）：120.11±5.10比24.37±1.85，脑组织TNF-α（ng/L）：165.20±6.31比14.89±0.83，均P＜0.01〕；与模型组比较，VNS组血浆和脑组织TNF-α含量均明显下降〔血浆TNF-α（ng/L）：46.72±4.90比120.11±5.10，脑组织TNF-α（ng/L）：107.95±1.83比165.20±6.31，均P＜0.01〕；而VGX组无此作用。光镜和透射电镜下观察显示，模型组、VGX组大鼠脑组织和神经元组织病理学改变较严重，而VNS组上述组织病理学改变明显减轻，但未完全消失。结论 LPS可以导致Objective To observe the effects of electrical stimulation of the vagus nerve on sepsis-associated encephalopathy, and to explore its possible mechanism. Methods Forty adult male Sprague-Dawley （ SD ） rats were randomly divided into sham group, model group, vagotomy group （ VGX group ）, vagus nerve stimulation group （ VNS group ）, with 10 rats in each group. The rat model of sepsis was reproduced by injecting lipopolysaccharide （ LPS ） through femoral vein, and rats of sham group were given the same volume of normal saline. The left cervical vagotomy was performed 30 minutes before LPS administration in VGX group, electrical stimulation of the left vagus nerve was initiated 30 minutes after LPS administration in VNS group. The rats in sham group were sacrificed after receiving electroencephalogram （ EEG ） examinations, and brain specimens were taken. The changes in EEG in the other three groups were monitored at 2, 4 and 6 hours after LPS administration, and the δ wave activity percentage was calculated. The blood was collected from abdominal aorta 6 hours after LPS administration, the rats were sacrificed and brain tissue was harvested. The concentrations of tumor necrosis factor-α （ TNF-α） in plasma and brain were measured with enzyme-linked immunosorbent assay （ ELISA ）. The histology and ultrastructure changes in the prefrontal cortex in the rats were observed with both light microscope and transmission electron microscope. Results Compared with sham group, the percentage of δ wave on EEG was significantly increased at 2, 4 and 6 hours after LPS administration in model group [ （ 14.52±0.50 ）%, （ 16.70±0.85 ）%, （ 17.35±0.36 ）% vs. （ 12.60±0.46 ）%, all P〈0.01 ]. It could be deduced that early brain dysfunction occurred in septic rats. Compared with model group, percentage of δ wave on EEG was significantly reduced at 2, 4, and 6 hours in VNS group [ （ 13.10±0.24 ）%vs. （ 14.52±0.50 ）%, （ 12.81±0.53 ）%vs. （ 16.70±0.85 ）%, （ 12.61±0.37 �

关 键 词：脓毒症 迷走神经 脓毒症相关性脑病 胆碱能抗炎通路 脑电图 

分 类 号：R459.7[医药卫生—急诊医学]