CAJ | 학술논문

目的探讨褪黑素(MT)对光气致大鼠肺损伤的抗氧化保护作用及其可能机制.方法 50只SD雄性大鼠随机分为光气染毒组、空气对照组、MT处理组、地塞米松处理组(DX处理组)和阴性对照组,每组10只,除空气对照组外吸入8.33 mg/L光气,染毒5 min,于染毒后1h分别从尾静脉注入MT(10 mg/kg)、地塞米松(2.5 mg/kg)、1％乙醇生理盐水(1 ml/kg),于6h后处死动物,测定肺组织湿干比,支气管肺泡灌洗液中总蛋白含量及中性粒细胞计数以及肺匀浆中丙二醛(MDA)含量,超氧化物歧化酶(SOD)及髓过氧化物酶(MPO)活力；光学显微镜下观察肺组织病理；蛋白质印迹(Western blot)法测定肺组织中诱导型一氧化氮合酶(iNOS)和核转录因子(NF-kB)的蛋白含量.结果与空对照气组比较,光气染毒组肺湿干比、BALF中中性粒细胞计数及蛋白含量均升高,差异有统计学意义(P＜0.01).光气染毒组大鼠肺组织中的MDA含量、MPO活力较空气对照组明显升高,差异有统计学意义(P＜0.05).与光气染毒组比较,MT处理组MDA含量和MPO活力均降低,SOD活力升高,差异有统计学意义(P＜0.01).与光气染毒组比较,MT处理组和DX处理组iNOS及NF-kB蛋白质表达均降低,差异有统计学意义(P＜0.01).结论 MT对光气致肺损伤有保护作用,其机制可能与清除自由基抗氧化及抑制iNOS、NF-kB的表达有关.
목적 탐토퇴흑소(MT)대광기치대서폐손상적항양화보호작용급기가능궤제.방법 50지SD웅성대서수궤분위광기염독조、공기대조조、MT처리조、지새미송처리조(DX처리조)화음성대조조,매조10지,제공기대조조외흡입8.33 mg/L광기,염독5 min,우염독후1h분별종미정맥주입MT(10 mg/kg)、지새미송(2.5 mg/kg)、1％을순생리염수(1 ml/kg),우6h후처사동물,측정폐조직습간비,지기관폐포관세액중총단백함량급중성립세포계수이급폐균장중병이철(MDA)함량,초양화물기화매(SOD)급수과양화물매(MPO)활력；광학현미경하관찰폐조직병리；단백질인적(Western blot)법측정폐조직중유도형일양화담합매(iNOS)화핵전록인자(NF-kB)적단백함량.결과 여공대조기조비교,광기염독조폐습간비、BALF중중성립세포계수급단백함량균승고,차이유통계학의의(P＜0.01).광기염독조대서폐조직중적MDA함량、MPO활력교공기대조조명현승고,차이유통계학의의(P＜0.05).여광기염독조비교,MT처리조MDA함량화MPO활력균강저,SOD활력승고,차이유통계학의의(P＜0.01).여광기염독조비교,MT처리조화DX처리조iNOS급NF-kB단백질표체균강저,차이유통계학의의(P＜0.01).결론 MT대광기치폐손상유보호작용,기궤제가능여청제자유기항양화급억제iNOS、NF-kB적표체유관.
Objective To investigate the antioxidant effect of melatonin (MT) in the rats with phosgene-induced lung injury and its possible mechanism.Methods Fifty male SD rats were equally randomized into phosgene exposure group,air control group,MT treatment group,dexamethasone (DX)treatment group,and negative control group.All groups except the air control group were exposed to 8.33 mg/L phosgene for 5 min,and the MT treatment group,DX treatment group,and negative control group were injected with MT (10 mg/kg),DX (2.5 mg/kg),and 1％ ethanol saline (1 ml/kg),respectively,via the caudal vein 1 hour after exposure.The rats were sacrificed 6 h later.Then,the wet/dry ratio of the lung,the total protein content and neutrophil count in bronchoalveolar lavage fluid (BALF),and the malonaldehyde (MDA) content and superoxide dismutase (SOD) and myeloperoxidase (MPO) activities in lung homogenate were measured;pathological observation was made on the lung tissue under an optical microscope; the protein expression of inducible nitric oxide synthase (iNOS) and NF-kB in the lung tissue was measured by Western blot.Results Compared with the air control group,the phosgene exposure group showed significantly increased wet/dry ratio of the lung and total protein content and neutrophil count in BALF (P＜0.01) as well as significantly increased MDA content and MPO activity in the lung tissue (P＜0.05).Compared with the phosgene exposure group,the MT treatment group showed significantly decreased MDA content and MPO activity and significantly increased SOD activity (P＜0.01),and the MT treatment group and DX treatment group showed significantly decreased protein expression of iNOS and NF-kB (P＜0.01).Conclusion MT has protective effect in phosgene-induced lung injury,and its protective mechanism may be associated with scavenging free radicals and inhibiting expression of iNOS and NF-kB.