CAJ | 학술논문

目的观察脂氧素A4类似物(LXA4-ME)对急性胰腺炎肺损伤(APALI)大鼠的保护作用.方法将90只SD大鼠随机分为假手术组、急性胰腺炎组(AP组)及LXA4-ME治疗组(LXA4-ME组),每组各30只.逆胰胆管注射5％牛磺胆酸钠(1 ml/kg)建立AP模型.LXA4-ME组在造模后尾静脉注射含LXA4-ME(87.5 μg/kg)的生理盐水1 ml.假手术组及AP组造模后经尾静脉注射等量生理盐水.于12、24 h观察胰腺、肺脏病理学变化、测定肺的干湿重比及血淀粉酶(AMY)水平.检测各组肺脏髓过氧化物酶(MPO)活性及丙二醛(MDA)含量.逆转录-聚合酶链反应( RT-PCR)法检测各组肺组织肿瘤坏死因子(TNF)-α、白细胞介素(IL) -1β、IL-6、细胞间黏附分子(ICAM)-1、E-选择素mRNA表达水平.结果 LXA4-ME组大鼠胰腺病理学评分(12 h:8.8±1.2、24 h:7.9±1.3)及肺脏病理学评分(12 h:3.35 ±0.78、24 h:3.29 ±0.64)均显著低于AP组胰腺(12h:11.6±1.4、24 h:11.5 ±0.7)、肺脏(12h:5.15 ±0.99、24 h:5.05 ±0.75)病理学评分(P＜0.01)；其12、24 h肺脏MPO活性[(18.06±0.69)、(19.52±0.76)U/g)]、MDA水平[(1.725 ±0.201)、(1.626±0.224) nmol/mg]均显著低于AP组MPO活性[(28.40±1.30)、(29.28±1.65) U/g)]及MDA水平[(2.412 ±0.279)、(2.518±0.216) nmol/mg)](P＜0.01)；其肺脏TNF-α、IL-1β、IL-6、ICAM-1、E-选择素的mRNA表达水平均显著低于AP组(P＜0.01).结论 LXA4-ME对APALI的保护作用可能与其减少肺组织中性粒细胞浸润、降低氧化应激水平、减少促炎性因子和黏附分子表达有关.
목적 관찰지양소A4유사물(LXA4-ME)대급성이선염폐손상(APALI)대서적보호작용.방법 장90지SD대서수궤분위가수술조、급성이선염조(AP조)급LXA4-ME치료조(LXA4-ME조),매조각30지.역이담관주사5％우광담산납(1 ml/kg)건립AP모형.LXA4-ME조재조모후미정맥주사함LXA4-ME(87.5 μg/kg)적생리염수1 ml.가수술조급AP조조모후경미정맥주사등량생리염수.우12、24 h관찰이선、폐장병이학변화、측정폐적간습중비급혈정분매(AMY)수평.검측각조폐장수과양화물매(MPO)활성급병이철(MDA)함량.역전록-취합매련반응( RT-PCR)법검측각조폐조직종류배사인자(TNF)-α、백세포개소(IL) -1β、IL-6、세포간점부분자(ICAM)-1、E-선택소mRNA표체수평.결과 LXA4-ME조대서이선병이학평분(12 h:8.8±1.2、24 h:7.9±1.3)급폐장병이학평분(12 h:3.35 ±0.78、24 h:3.29 ±0.64)균현저저우AP조이선(12h:11.6±1.4、24 h:11.5 ±0.7)、폐장(12h:5.15 ±0.99、24 h:5.05 ±0.75)병이학평분(P＜0.01)；기12、24 h폐장MPO활성[(18.06±0.69)、(19.52±0.76)U/g)]、MDA수평[(1.725 ±0.201)、(1.626±0.224) nmol/mg]균현저저우AP조MPO활성[(28.40±1.30)、(29.28±1.65) U/g)]급MDA수평[(2.412 ±0.279)、(2.518±0.216) nmol/mg)](P＜0.01)；기폐장TNF-α、IL-1β、IL-6、ICAM-1、E-선택소적mRNA표체수평균현저저우AP조(P＜0.01).결론 LXA4-ME대APALI적보호작용가능여기감소폐조직중성립세포침윤、강저양화응격수평、감소촉염성인자화점부분자표체유관.
Objective To investigate the protective effects of lipoxin A4 analogue (LXA4)-ME on acute pancreatitis associated with lung injury (APALI).Methods Ninety male SD rats were randomly divided into sham operation group (n =30),AP group (n =30) and LXA4-ME group (n =30).AP was induced by retrograde injection of 5％ sodium taurocholate ( 1 ml/kg) into the pancreatic duct.In LXA4-ME group,LXA4-ME was administered (87.5 μg/kg) intraveneously after the onset of AP. Sham operation group was given normal saline after the sham operation.The rats were sacrificed at 12 and 24 h after induction of pancreatitis.The serum level of amylase was measured.The histological changes of the pancreas and lung were observed.The activities of myeloperoxidase (MPO) and levels of malondialdehyde (MDA) in the lung tissue were determined.The mRNA levels of tumor necrotizing factor (TNF)-α,interleukin (IL) -1β,IL-6,intercelluar adhesion molecules (ICAM)-1,E-selectin in the lung tissue were measured by using reverse transcription-polymerase chain reaction (RT-PCR).Results The pathological scores of the pancreas [ 12 h:(8.8 ± 1.2),24 h:(7.9 ± 1.3) ] and lung [ (12 h:(3.35 ±0.78),24 h:(3.29 ±0.64) were lower in LXA4-ME group than in AP group [t2h:(11.6±1.4),24h:(11.5±0.7) for the pancreas,and 12 h:(5.15 ±0.99),24 h:(5.05 ±0.75) for the lung] (allP＜0.01).The activity of MPO [(18.06±0.69),(19.52 ±0.76) U/g] and the levelofMDA [(1.725±0.201),(1.626 ±0.224)nmol/mg] at 12 and 24 h in the lung tissue in LXA4-ME group was significantly lower than MPO [ (28.40 ±1.30),(29.28 ± 1.65) U/g] and MDA [ (2.412 ±0.279),(2.518 ±0.216) nmol/mg] in AP group.The expression of the cytokine TNF-α,IL-1β,IL-6,ICAM-1,and E-selectin in the lung tissue in LXA4-ME group was lower than that in AP group (all P ＜ 0.01 ).Conclusion The protective effect of LXA4-ME on APALI is associated with the reduction of neutrophil infiltration and oxidative stress levels.The mechanism may be due to the suppression of expression of pro-inflammatory cytokines and cell adhesion molecules.