CAJ | 학술논문

目的评价姜黄素预先给药对兔呼吸机相关性肺损伤核因子E2相关因子2(Nrf2)蛋白表达的影响.方法健康成年雄性新西兰大白兔24只,3～6月龄,体重2.5 ～ 3.0 kg,采用随机数字表法分为3组(n=8):双肺通气组(TLV组)、单肺通气组(OLV组)和姜黄素预先给药组(Cur组).于通气前7d开始灌胃给药,Cur组给予姜黄素40 mg/kg(溶于2ml 1％羟甲基纤维素钠),TLV组和OLV组给予等量羟甲基纤维素钠,每天早晚各1次.行气管切开术,TLV组采用单腔气管导管置入气管行双肺通气,OLV组和Cur组采用单腔气管导管置入右主支气管行单肺通气.3组均采用容量通气模式,调整通气参数,维持SpO2＞90％.于通气开始即刻(T0)、通气1、2和3 h(T1-3)时采集右股动脉血样行血气分析,测定PaO2,计算氧合指数.通气3h时处死兔,取右肺称湿重,然后取下叶肺组织,采用化学比色法测定肺组织丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性;光镜下观察肺组织病理学结果并行肺组织病理学损伤评分,Western blot法检测Nrf2和HO-1蛋白表达,将右肺烘烤后称干重,计算右肺湿/干重比值(W/D比值).结果与TLV组比较,OLV组和Cur组W/D比值、肺损伤评分、MDA含量、Nrf2和HO-1蛋白表达水平升高,SOD活性和T23时氧合指数降低(P＜0.05);与OLV组比较,Cur组W/D比值、肺损伤评分、MDA含量下降,SOD活性、T3时氧合指数、Nrf2和HO-1蛋白表达水平升高(P＜ 0.05).结论姜黄素预先给药通过促进肺组织Nrf2蛋白表达减轻兔呼吸机相关性肺损伤.
목적 평개강황소예선급약대토호흡궤상관성폐손상핵인자E2상관인자2(Nrf2)단백표체적영향.방법 건강성년웅성신서란대백토24지,3～6월령,체중2.5 ～ 3.0 kg,채용수궤수자표법분위3조(n=8):쌍폐통기조(TLV조)、단폐통기조(OLV조)화강황소예선급약조(Cur조).우통기전7d개시관위급약,Cur조급여강황소40 mg/kg(용우2ml 1％간갑기섬유소납),TLV조화OLV조급여등량간갑기섬유소납,매천조만각1차.행기관절개술,TLV조채용단강기관도관치입기관행쌍폐통기,OLV조화Cur조채용단강기관도관치입우주지기관행단폐통기.3조균채용용량통기모식,조정통기삼수,유지SpO2＞90％.우통기개시즉각(T0)、통기1、2화3 h(T1-3)시채집우고동맥혈양행혈기분석,측정PaO2,계산양합지수.통기3h시처사토,취우폐칭습중,연후취하협폐조직,채용화학비색법측정폐조직병이철(MDA)함량、초양화물기화매(SOD)활성;광경하관찰폐조직병이학결과병행폐조직병이학손상평분,Western blot법검측Nrf2화HO-1단백표체,장우폐홍고후칭간중,계산우폐습/간중비치(W/D비치).결과 여TLV조비교,OLV조화Cur조W/D비치、폐손상평분、MDA함량、Nrf2화HO-1단백표체수평승고,SOD활성화T23시양합지수강저(P＜0.05);여OLV조비교,Cur조W/D비치、폐손상평분、MDA함량하강,SOD활성、T3시양합지수、Nrf2화HO-1단백표체수평승고(P＜ 0.05).결론 강황소예선급약통과촉진폐조직Nrf2단백표체감경토호흡궤상관성폐손상.
Objective To evaluate the effects of curcumin pretreatment on the expression of Nrf2 protein during ventilator-induced lung injury in rabbits.Methods Twenty-four healthy male New Zealand white rabbits,aged 3-6 months,weighing 2.5-3.0 kg,were randomized into 3 groups (n =8 each) using a random number table:two-lung ventilation (TLV) group; one-lung ventilation (OLV) group; and curcumin pretreatment group (group Cur).In group Cur,curcumin 40 mg/kg (dissolved in 2 ml of 1％ sodium carboxymethylcellulose) was given via a gastric tube into the stomach twice a day for 7 consecutive days starting from 7 days before ventilation,while the equal volume of sodium carboxymethylcellulose was given via a gastric tube instead of curcumin in TLV and OLV groups.All the rabbits were tracheostomized,and a tracheal tube was inserted to perform TLV in TLV group,and a tracheal tube was inserted into the right bronchus to establish OLV in OLV and Cur groups.Volumecontrolled ventilation was used in the three groups and the ventilatory parameters were regulated to maintain SpO2 ＞ 90 ％.Immediately before beginning of ventilation (T0) and at 1,2 and 3 h of ventilation (T1-3),arterial blood samples were obtained for blood gas analysis and determination of PaO2.The oxygenation index was calculated.At the end of ventilation,the rabbits were sacrificed and right lungs were removed for determination of wet/dry lung weight ratio (W/D ratio).The right lower lobe was isolated and puhmonary specimens were obtained for determination of malondialdehyde (MDA) content and superoxide dismutase (SOD) activity (using colorimetric method) and the expression of Nrf2 and HO-1 protein (by Western blot) in lung tissues and for microscopic examination of pathological changes of the lung which were scored.Results Compared with group TLV,the W/D ratio,pathological scores,MDA content,and expression of Nrf2 and HO-1 were significantly increased,and the SOD activity and oxygenation index at T2,3 were decreased in OLV and Cur groups (P ＜ 0.05).Compared with group OLV,the W/D ratio,pathological scores,and MDA content were significantly decreased,and the SOD activity,oxygenation index at T3,and expression of Nrf2 and HO-1 were increased in group Cur (P ＜ 0.05).Conclusion Curcumin pretreatment reduces ventilator-induced lung injury through promoting the expression of Nrf2 protein in lung tissues in rabbits.