国际麻醉学与复苏杂志
國際痳醉學與複囌雜誌
국제마취학여복소잡지
INTERNATIONAL JOURNAL OF ANESTHESIOLOGY AND RESUSCITATION
2014年
3期
203-206
,共4页
杨颖%王鹏%封光%刘功俭
楊穎%王鵬%封光%劉功儉
양영%왕붕%봉광%류공검
右美托咪定%抗炎%p38丝裂原激活的蛋白激酶%内毒素%急性肺损伤
右美託咪定%抗炎%p38絲裂原激活的蛋白激酶%內毒素%急性肺損傷
우미탁미정%항염%p38사렬원격활적단백격매%내독소%급성폐손상
Dexmedetomidine%Anti-inflammatory effect%p38 mitogen-activated protein kinase%Lipopolysaccharides%Acute lung injury
目的 探讨右美托咪定(dexmedetomidine,Dex)对内毒素(lipopolysaccharides,LPS)诱导的急性肺损伤(acutelung injury,ALI)大鼠肺部P38丝裂原活化蛋白激酶(p38 mitogen-activated protein kinase,p38MAPK)和炎症反应的影响. 方法 健康成年雄性SD大鼠采用完全随机分组法分为5组,每组10只:生理盐水组(C组),LPS组,0.2 μg·kg-1·h-1 Dex处理组(Dex0.2组),1μg·kg-1·h-1 Dex处理组(Dex1组),5 μg·kg-1·h-1 Dex处理组(Dex5组).各Dex处理组在给予LPS(腹腔注射LPS8 mg/kg)诱导ALI之前输注Dex负荷剂量1μg· kg-1·h-1 10 min,然后持续按各处理组相应剂量输注Dex至各时间点.C组与LPS组输注等体积的生理盐水(1ml·kg-1·h-1)至各时间点.收集肺泡灌洗液(bronchoalveolar lavage fluid,BALF),动脉血和肺组织标本,进行动脉血气分析,测量肺组织湿/干重比,观察肺病理学改变,检测支气管BALF中肿瘤坏死因子-α(tumour necrosis factor-α,TNF-α)和白介素(interleukin,IL)-10的浓度,利用Western blot检测各组大鼠肺组织中p38MAPK和磷酸化水平.结果 在注射了LPS后,各组大鼠的动脉氧分压均明显降低(61.3±1.2) vs (131.7±4.7)(P＜0.05);C组大鼠肺部未见明显的病理改变,LPS组、Dex0.2组和Dex1组大鼠肺部有明显的病理改变,而Dex5组大鼠肺部病理改变较LPS组明显减轻;肺组织湿/干重比LPS组明显的高于C组(5.4±0.3)vs(3.6±0.3)(P＜0.05),Dex5组明显低于LPS组(4.4±0.4)vs(5.4±0.3) (P＜0.05);磷酸化的p38MAPK、支气管BALF中TNF-α和IL-10水平,LPS组、Dex0.2组和Dex1组明显高于C组(P＜0.05),Dex5组明显低于LPS组(P＜0.05). 结论 Dex能够减轻LPS造成的大鼠ALI,其机制可能部分与阻断P38MAPK的活化及肺部炎症有关.
目的 探討右美託咪定(dexmedetomidine,Dex)對內毒素(lipopolysaccharides,LPS)誘導的急性肺損傷(acutelung injury,ALI)大鼠肺部P38絲裂原活化蛋白激酶(p38 mitogen-activated protein kinase,p38MAPK)和炎癥反應的影響. 方法 健康成年雄性SD大鼠採用完全隨機分組法分為5組,每組10隻:生理鹽水組(C組),LPS組,0.2 μg·kg-1·h-1 Dex處理組(Dex0.2組),1μg·kg-1·h-1 Dex處理組(Dex1組),5 μg·kg-1·h-1 Dex處理組(Dex5組).各Dex處理組在給予LPS(腹腔註射LPS8 mg/kg)誘導ALI之前輸註Dex負荷劑量1μg· kg-1·h-1 10 min,然後持續按各處理組相應劑量輸註Dex至各時間點.C組與LPS組輸註等體積的生理鹽水(1ml·kg-1·h-1)至各時間點.收集肺泡灌洗液(bronchoalveolar lavage fluid,BALF),動脈血和肺組織標本,進行動脈血氣分析,測量肺組織濕/榦重比,觀察肺病理學改變,檢測支氣管BALF中腫瘤壞死因子-α(tumour necrosis factor-α,TNF-α)和白介素(interleukin,IL)-10的濃度,利用Western blot檢測各組大鼠肺組織中p38MAPK和燐痠化水平.結果 在註射瞭LPS後,各組大鼠的動脈氧分壓均明顯降低(61.3±1.2) vs (131.7±4.7)(P＜0.05);C組大鼠肺部未見明顯的病理改變,LPS組、Dex0.2組和Dex1組大鼠肺部有明顯的病理改變,而Dex5組大鼠肺部病理改變較LPS組明顯減輕;肺組織濕/榦重比LPS組明顯的高于C組(5.4±0.3)vs(3.6±0.3)(P＜0.05),Dex5組明顯低于LPS組(4.4±0.4)vs(5.4±0.3) (P＜0.05);燐痠化的p38MAPK、支氣管BALF中TNF-α和IL-10水平,LPS組、Dex0.2組和Dex1組明顯高于C組(P＜0.05),Dex5組明顯低于LPS組(P＜0.05). 結論 Dex能夠減輕LPS造成的大鼠ALI,其機製可能部分與阻斷P38MAPK的活化及肺部炎癥有關.
목적 탐토우미탁미정(dexmedetomidine,Dex)대내독소(lipopolysaccharides,LPS)유도적급성폐손상(acutelung injury,ALI)대서폐부P38사렬원활화단백격매(p38 mitogen-activated protein kinase,p38MAPK)화염증반응적영향. 방법 건강성년웅성SD대서채용완전수궤분조법분위5조,매조10지:생리염수조(C조),LPS조,0.2 μg·kg-1·h-1 Dex처리조(Dex0.2조),1μg·kg-1·h-1 Dex처리조(Dex1조),5 μg·kg-1·h-1 Dex처리조(Dex5조).각Dex처리조재급여LPS(복강주사LPS8 mg/kg)유도ALI지전수주Dex부하제량1μg· kg-1·h-1 10 min,연후지속안각처리조상응제량수주Dex지각시간점.C조여LPS조수주등체적적생리염수(1ml·kg-1·h-1)지각시간점.수집폐포관세액(bronchoalveolar lavage fluid,BALF),동맥혈화폐조직표본,진행동맥혈기분석,측량폐조직습/간중비,관찰폐병이학개변,검측지기관BALF중종류배사인자-α(tumour necrosis factor-α,TNF-α)화백개소(interleukin,IL)-10적농도,이용Western blot검측각조대서폐조직중p38MAPK화린산화수평.결과 재주사료LPS후,각조대서적동맥양분압균명현강저(61.3±1.2) vs (131.7±4.7)(P＜0.05);C조대서폐부미견명현적병리개변,LPS조、Dex0.2조화Dex1조대서폐부유명현적병리개변,이Dex5조대서폐부병리개변교LPS조명현감경;폐조직습/간중비LPS조명현적고우C조(5.4±0.3)vs(3.6±0.3)(P＜0.05),Dex5조명현저우LPS조(4.4±0.4)vs(5.4±0.3) (P＜0.05);린산화적p38MAPK、지기관BALF중TNF-α화IL-10수평,LPS조、Dex0.2조화Dex1조명현고우C조(P＜0.05),Dex5조명현저우LPS조(P＜0.05). 결론 Dex능구감경LPS조성적대서ALI,기궤제가능부분여조단P38MAPK적활화급폐부염증유관.
Objective The aim of this study was to determine whether dexmedetomidine (Dex) could diminish lipopolysaccharide(LPS)-induced pulmonary injury by blocking lung p38 mitogen-activated protein kinase(p38MAPK) activation and inflammation in rats.Methods A total of 50 adult male SD rats were assigned to one of five groups:0.9％ sodium chloride group (C group),LPS group (LPS group) and LPS plus Dex groups (0.2,1,5 μg/kg per hour) (Dex0.2 group,Dex1 group and Dex5 group).The rats in the LPS plus Dex groups were injected a loading dose of Dex (1 μg/kg per hour,intravenous infusion over 10 minutes) followed by LPS administration and Dex infusion at different doses (0.2,1,5 μg/kg per hour,respectively) until the end of experiment.Simultaneously,the LPS and control groups received an equal volume of 0.9％ sodium chloride(1 ml/kg per hour) till the end of experiment.Western blot was used to detect the expression of phosphorylation of p38MAPK in lung tissues.Additionally,we examined the concentration of tumour necrosis factor-α(TNF-α) and interleukin(IL)-10 in bronchoalveolar lavage fluid(BALF),the histopathologic changes of lung,arterial blood gases and lung water content.Results With the administration of LPS,arterial oxygen partial pressure was significantly decreased (61.3±1.2) vs (131.7±4.7) (P＜0.05),Pathological examination showed that the normal structure of lung was destroyed badly after LPS injection,including intra-alveolar hemorrhage,interstitial edema,alveolar collapse and massive inflammatory cells infiltration,The lung water content was significantly increased (5.4±0.3) vs (3.6±0.2)(P＜ 0.05).Compared with the LPS group,lung water content of Dex5 group was significantly decreased(4.4±0.4) vs (5.4±0.3)(P＜0.05).With the administration of LPS,the phospho-p38 MAPK substantially increased immediately,and the concentrations of cytokines were also increased.However,Dex at the dose of 5.0 μg/kg per hour,but not at 0.2 or 1.0 μg/kg per hour,significantly attenuated these effects of LPS (P＜0.05).Conclusions Dex may attenuate LPS-induced acute lung injury via inhibiting p38MAPK activation and lung inflammation.
