摘要
目的 评价p38丝裂原活化蛋白激酶（p38MAPK）信号通路在电针减轻内毒素休克诱发兔急性肺损伤中的作用及其与核因子E2相关因子2（Nrf2）的关系.方法 健康雄性新西兰大白兔70只,2月龄,体重1.5 ～ 2.5 kg,采用随机数字表法分为7组（n=10）：对照组（C组）、内毒素休克诱发急性肺损伤模型组（A组）、p38MAPK抑制剂组（SB组）、模型＋p38MAPK抑制剂组（A-SB组）、模型＋电针组（A-EA组）、模型＋电针非穴位组（A-NEA组）和模型＋电针穴位＋p38MAPK抑制剂组（A-EA-SB组）.模型制备前1～4d及模型制备过程中,A-EA组和A-EA-SB组电针刺激穴位,采用疏密波2/100 Hz,强度以出现轻微肌颤为宜,30 min/次,1次/d,A-NEA组采用同样的频率以及强度电针刺激穴位旁开0.5 cm处,A组、A-SB组、A-EA组、A-NEA组和A-EA-SB组静脉注射内毒素5 mg/kg,C组和SB组给予等容量生理盐水.模型制备成功后SB组、A-SB组和A-EA-SB组静脉注射p38MAPK抑制剂5μmol/kg,C组给予等容量生理盐水,其余各组给予等容量无水乙醇.静脉注射内毒素或生理盐水后6h,取颈动脉血样行血气分析后放血处死动物,取肺组织行病理学观察并进行肺损伤评分,计算肺湿重/干重（W/D）比值,测定肺组织MDA含量及SOD活性,检测磷酸化p38MAPK（p-p38MAPK）及Nrf2表达水平.结果 与C组比较,A组、A-SB组、A-EA组、A-NEA组和A-EA-SB组肺损伤评分、W/D比值、肺组织MDA含量、p-p38MAPK及Nrf2表达水平升高,SOD活性降低（P＜0.05）;与A组比较,A-EA组和A-EA-SB组肺损伤评分、W/D比值、肺组织MDA含量降低,SOD活性、p-p38MAPK及Nrf2表达水平升高（P＜0.05）;与A-EA组比较,A-EA-SB组肺损伤评分、W/D比值、肺组织MDA含量升高,SOD活性、p-p38MAPK及Nrf2表达水平降低（P＜0.05）.结论 p38MAPK信号通路介导了电针减轻内毒素休克诱发兔急性肺损伤,其机制与其上调Nrf2表达有关.
Objective To evaluate the role of p38MAPK signaling pathway in electroacupuncture （EA）-induced reduction of acute lung injury （ALI） in rabbits with endotoxic shock and the relationship with nuclear factor E2-related factor 2 （Nrf2）.Methods Seventy healthy male New Zealand white rabbits,aged 2 months,weighing 1.5-2.5 kg,were randomly divided into 7 groups （n=10 each） using a random number table：control group （group C）,endotoxin-induced ALI group （group A）,p38MAPK inhibitor SB203580 group （group SB）,ALI ＋ SB203580 group （group A-SB）,ALI ＋ EA group （A-EA group）,ALI ＋ EA at non-acupoint group （A-NEA group） and ALI ＋ EA at acupoints＋ SB203580 group （A-EA-SB group）.The rabbits were anesthetized with urethane and tracheostomized and kept spontaneous breathing.Right common carotid artery was cannulated for mean arterial pressure monitoring.The auricular vein was cannulated for drug administration.Bilateral 30 min EA （wave length 0.2-0.6 ms,frequency 2/100 Hz,intensity ≤ 1-2 mA） stimulation of Zusanli and Feishu was performed once a day for 4 days before establishment of the model and during establishment of the model in A-EA and A-EA-SB groups.In group A-NEA,EA was performed at the points 0.5 cm lateral to the acupoints of Zusanli and Feishu according to the method previously described in group EA.In A,A-SB,A-EA,A-NEA and A-EA-SB groups,ALI was induced by endotoxin （5 mg/kg） injection,while the equal volume of normal saline was given in C and SB groups.After establishment of the model,SB203580 5 μmol/kg was injected intravenously in SB,A-SB and A-EA-SB groups,the equal volume of normal saline was given in group C,and the equal volume of dehydrated alcohol was given in the other groups.At 6 h after endotoxin or normal saline administration,arterial blood samples were collected for blood gas analysis.The rabbits were then sacrificed,and lungs were removed for microscopic examination and for determination of malondialdehyde （MDA） content,superoxide dismu
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2015年第4期481-485,共5页
Chinese Journal of Anesthesiology
基金
国家自然科学基金（81372096）
天津市科技支撑计划重点项目（12ZCZDSY03300）
