中华麻醉学杂志
中華痳醉學雜誌
중화마취학잡지
CHINESE JOURNAL OF ANESTHESIOLOGY
2015年
4期
481-485
,共5页
高雪松%宫丽荣%余剑波%史佳%董树安%吴丽丽%张圆
高雪鬆%宮麗榮%餘劍波%史佳%董樹安%吳麗麗%張圓
고설송%궁려영%여검파%사가%동수안%오려려%장원
p38丝裂原活化蛋白激酶类%电刺激疗法%休克,脓毒性%呼吸窘迫综合征,成人%NF-E2相关因子2
p38絲裂原活化蛋白激酶類%電刺激療法%休剋,膿毒性%呼吸窘迫綜閤徵,成人%NF-E2相關因子2
p38사렬원활화단백격매류%전자격요법%휴극,농독성%호흡군박종합정,성인%NF-E2상관인자2
p38 mitogen-activated protein kinases%Electric stimulation therapy%Shock,septic%Respiratory distress syndrome,adult%NF-E2-related factor 2
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.
目的 評價p38絲裂原活化蛋白激酶(p38MAPK)信號通路在電針減輕內毒素休剋誘髮兔急性肺損傷中的作用及其與覈因子E2相關因子2(Nrf2)的關繫.方法 健康雄性新西蘭大白兔70隻,2月齡,體重1.5 ～ 2.5 kg,採用隨機數字錶法分為7組(n=10):對照組(C組)、內毒素休剋誘髮急性肺損傷模型組(A組)、p38MAPK抑製劑組(SB組)、模型+p38MAPK抑製劑組(A-SB組)、模型+電針組(A-EA組)、模型+電針非穴位組(A-NEA組)和模型+電針穴位+p38MAPK抑製劑組(A-EA-SB組).模型製備前1～4d及模型製備過程中,A-EA組和A-EA-SB組電針刺激穴位,採用疏密波2/100 Hz,彊度以齣現輕微肌顫為宜,30 min/次,1次/d,A-NEA組採用同樣的頻率以及彊度電針刺激穴位徬開0.5 cm處,A組、A-SB組、A-EA組、A-NEA組和A-EA-SB組靜脈註射內毒素5 mg/kg,C組和SB組給予等容量生理鹽水.模型製備成功後SB組、A-SB組和A-EA-SB組靜脈註射p38MAPK抑製劑5μmol/kg,C組給予等容量生理鹽水,其餘各組給予等容量無水乙醇.靜脈註射內毒素或生理鹽水後6h,取頸動脈血樣行血氣分析後放血處死動物,取肺組織行病理學觀察併進行肺損傷評分,計算肺濕重/榦重(W/D)比值,測定肺組織MDA含量及SOD活性,檢測燐痠化p38MAPK(p-p38MAPK)及Nrf2錶達水平.結果 與C組比較,A組、A-SB組、A-EA組、A-NEA組和A-EA-SB組肺損傷評分、W/D比值、肺組織MDA含量、p-p38MAPK及Nrf2錶達水平升高,SOD活性降低(P＜0.05);與A組比較,A-EA組和A-EA-SB組肺損傷評分、W/D比值、肺組織MDA含量降低,SOD活性、p-p38MAPK及Nrf2錶達水平升高(P＜0.05);與A-EA組比較,A-EA-SB組肺損傷評分、W/D比值、肺組織MDA含量升高,SOD活性、p-p38MAPK及Nrf2錶達水平降低(P＜0.05).結論 p38MAPK信號通路介導瞭電針減輕內毒素休剋誘髮兔急性肺損傷,其機製與其上調Nrf2錶達有關.
목적 평개p38사렬원활화단백격매(p38MAPK)신호통로재전침감경내독소휴극유발토급성폐손상중적작용급기여핵인자E2상관인자2(Nrf2)적관계.방법 건강웅성신서란대백토70지,2월령,체중1.5 ～ 2.5 kg,채용수궤수자표법분위7조(n=10):대조조(C조)、내독소휴극유발급성폐손상모형조(A조)、p38MAPK억제제조(SB조)、모형+p38MAPK억제제조(A-SB조)、모형+전침조(A-EA조)、모형+전침비혈위조(A-NEA조)화모형+전침혈위+p38MAPK억제제조(A-EA-SB조).모형제비전1～4d급모형제비과정중,A-EA조화A-EA-SB조전침자격혈위,채용소밀파2/100 Hz,강도이출현경미기전위의,30 min/차,1차/d,A-NEA조채용동양적빈솔이급강도전침자격혈위방개0.5 cm처,A조、A-SB조、A-EA조、A-NEA조화A-EA-SB조정맥주사내독소5 mg/kg,C조화SB조급여등용량생리염수.모형제비성공후SB조、A-SB조화A-EA-SB조정맥주사p38MAPK억제제5μmol/kg,C조급여등용량생리염수,기여각조급여등용량무수을순.정맥주사내독소혹생리염수후6h,취경동맥혈양행혈기분석후방혈처사동물,취폐조직행병이학관찰병진행폐손상평분,계산폐습중/간중(W/D)비치,측정폐조직MDA함량급SOD활성,검측린산화p38MAPK(p-p38MAPK)급Nrf2표체수평.결과 여C조비교,A조、A-SB조、A-EA조、A-NEA조화A-EA-SB조폐손상평분、W/D비치、폐조직MDA함량、p-p38MAPK급Nrf2표체수평승고,SOD활성강저(P＜0.05);여A조비교,A-EA조화A-EA-SB조폐손상평분、W/D비치、폐조직MDA함량강저,SOD활성、p-p38MAPK급Nrf2표체수평승고(P＜0.05);여A-EA조비교,A-EA-SB조폐손상평분、W/D비치、폐조직MDA함량승고,SOD활성、p-p38MAPK급Nrf2표체수평강저(P＜0.05).결론 p38MAPK신호통로개도료전침감경내독소휴극유발토급성폐손상,기궤제여기상조Nrf2표체유관.
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 dismutase (SOD) activity,and expression of phosphor-p38MAPK (p-p38MAPK) and Nrf2 in lung tissues.The pathological changes of lungs were scored.Wet to dry lung weight ratio (W/D ratio) was calculated.Results Compared to group C,the pathological scores,W/D ratio,MDA content,and expression of pp38MAPK and Nrf2 were significantly increased,and SOD activities were decreased in A,A-SB,A-EA,ANEA and A-EA-SB groups.Compared to group A,the pathological scores,W/D ratio and MDA content were significantly decreased,and SOD activities and expression of p-p38MAPK and Nrf2 were increased in A-EA group.Compared to group A-EA,the pathological scores,W/D ratio and MDA content were significantly increased,and SOD activities and expression of p-p38MAPK and Nrf2 were significantly decreased in group A-EA-SB.Conclusion p38MAPK signaling pathway mediates EA-induced reduction of ALI in rabbits with endotoxic shock,and up-regulated expression of Nrf2 is involved in the mechanism.
