中华危重病急救医学
中華危重病急救醫學
중화위중병급구의학
Chinese Critical Care Medicine
2015年
6期
509-513
,共5页
李娜%李志峰%项辉%王翔%张雪艳%李建国
李娜%李誌峰%項輝%王翔%張雪豔%李建國
리나%리지봉%항휘%왕상%장설염%리건국
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
膿毒癥%迷走神經%膿毒癥相關性腦病%膽堿能抗炎通路%腦電圖
농독증%미주신경%농독증상관성뇌병%담감능항염통로%뇌전도
Sepsis%Vagus nerve%Sepsis-associated encephalopathy%Anti-inflammatory effect of cholinergic pathway%Electroencephalogram
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可以导致大鼠发生脓毒症相关性脑病；电刺激迷走神经可激活胆碱能抗炎通路，通过减轻全身和脑组织的炎症反应，改善脑功能，抑制脓毒症相关性脑病的发展。
目的：觀察電刺激迷走神經對膿毒癥相關性腦病的影響，併探討其可能的作用機製。方法將40隻成年雄性SD大鼠按隨機數字錶法分為假手術組、模型組、迷走神經切斷組（VGX組）、迷走神經刺激組（VNS組），每組10隻。經股靜脈註射脂多糖（LPS）10 mg/kg製備膿毒癥大鼠模型，假手術組給予等量生理鹽水；VGX組製模前30 min行左頸部迷走神經切除術，VNS組製模後30 min開始刺激左頸部迷走神經。假手術組行腦電圖檢查後處死大鼠併留取標本，其他3組于製模後2、4和6h鑑測腦電圖改變，計算δ波百分比；製模後6 h經腹主動脈取血後處死大鼠取腦組織，採用酶聯免疫吸附試驗（ELISA）檢測血漿和腦組織中TNF-α含量；光鏡和透射電鏡下觀察大鼠前額葉皮質組織病理學和超微結構改變。結果與假手術組比較，模型組製模後2、4和6 h腦電圖δ波百分比明顯增加〔（14.52±0.50）%、（16.70±0.85）%、（17.35±0.36）%比（12.60±0.46）%，均P＜0.01〕，可判斷膿毒癥大鼠髮生瞭早期腦功能障礙。與模型組比較，VNS組製模後2、4、6 h腦電圖δ波百分比均明顯減少〔（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組無此作用。與假手術組比較，模型組血漿和腦組織TNF-α含量均明顯增高〔血漿TNF-α（ng/L）：120.11±5.10比24.37±1.85，腦組織TNF-α（ng/L）：165.20±6.31比14.89±0.83，均P＜0.01〕；與模型組比較，VNS組血漿和腦組織TNF-α含量均明顯下降〔血漿TNF-α（ng/L）：46.72±4.90比120.11±5.10，腦組織TNF-α（ng/L）：107.95±1.83比165.20±6.31，均P＜0.01〕；而VGX組無此作用。光鏡和透射電鏡下觀察顯示，模型組、VGX組大鼠腦組織和神經元組織病理學改變較嚴重，而VNS組上述組織病理學改變明顯減輕，但未完全消失。結論 LPS可以導緻大鼠髮生膿毒癥相關性腦病；電刺激迷走神經可激活膽堿能抗炎通路，通過減輕全身和腦組織的炎癥反應，改善腦功能，抑製膿毒癥相關性腦病的髮展。
목적：관찰전자격미주신경대농독증상관성뇌병적영향，병탐토기가능적작용궤제。방법장40지성년웅성SD대서안수궤수자표법분위가수술조、모형조、미주신경절단조（VGX조）、미주신경자격조（VNS조），매조10지。경고정맥주사지다당（LPS）10 mg/kg제비농독증대서모형，가수술조급여등량생리염수；VGX조제모전30 min행좌경부미주신경절제술，VNS조제모후30 min개시자격좌경부미주신경。가수술조행뇌전도검사후처사대서병류취표본，기타3조우제모후2、4화6h감측뇌전도개변，계산δ파백분비；제모후6 h경복주동맥취혈후처사대서취뇌조직，채용매련면역흡부시험（ELISA）검측혈장화뇌조직중TNF-α함량；광경화투사전경하관찰대서전액협피질조직병이학화초미결구개변。결과여가수술조비교，모형조제모후2、4화6 h뇌전도δ파백분비명현증가〔（14.52±0.50）%、（16.70±0.85）%、（17.35±0.36）%비（12.60±0.46）%，균P＜0.01〕，가판단농독증대서발생료조기뇌공능장애。여모형조비교，VNS조제모후2、4、6 h뇌전도δ파백분비균명현감소〔（13.10±0.24）%비（14.52±0.50）%，（12.81±0.53）%비（16.70±0.85）%，（12.62±0.37）%비（17.35±0.36）%，균P＜0.01〕；이VGX조무차작용。여가수술조비교，모형조혈장화뇌조직TNF-α함량균명현증고〔혈장TNF-α（ng/L）：120.11±5.10비24.37±1.85，뇌조직TNF-α（ng/L）：165.20±6.31비14.89±0.83，균P＜0.01〕；여모형조비교，VNS조혈장화뇌조직TNF-α함량균명현하강〔혈장TNF-α（ng/L）：46.72±4.90비120.11±5.10，뇌조직TNF-α（ng/L）：107.95±1.83비165.20±6.31，균P＜0.01〕；이VGX조무차작용。광경화투사전경하관찰현시，모형조、VGX조대서뇌조직화신경원조직병이학개변교엄중，이VNS조상술조직병이학개변명현감경，단미완전소실。결론 LPS가이도치대서발생농독증상관성뇌병；전자격미주신경가격활담감능항염통로，통과감경전신화뇌조직적염증반응，개선뇌공능，억제농독증상관성뇌병적발전。
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 )%vs. ( 17.35±0.36 )%, all P < 0.01 ], while there was no such effect in the VGX group. Compared with sham group, the concentrations of TNF-α in plasma and brain were all increased in model group [ plasma TNF-α( ng/L ): 120.11±5.10 vs. 24.37±1.85, brain TNF-α( ng/L ):165.20±6.31 vs. 14.89±0.83, both P<0.01 ]. Compared with model group, the concentrations of TNF-αin plasma and brain were all significantly decreased in VNS group [ plasma TNF-α( ng/L ):46.72±4.90 vs. 120.11±5.10, brain TNF-α( ng/L ):107.95±1.83 vs. 165.20±6.31, both P<0.01 ], while there was no such effect in the VGX group. Light microscope and transmission electron microscope showed that the damage of brain tissue and neurons in model group and VGX group was more obvious, while that in the VNS group was less severe, though not completely disappeared. Conclusions LPS can lead to sepsis-associated encephalopathy in rats. It was shown that electrical stimulation of the vagus nerve can activate anti-inflammatory effect through cholinergic pathway, and improve the cerebral function, and inhibit the development of sepsis-associated encephalopathy by reducing systemic and cerebral inflammatory reaction.
