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目的:探讨布地奈德(Budesonide)联合特布他林(Terbutaline)雾化吸入及前列腺素E1(Prostaglandin E1,PGE1)雾化吸入对高氧诱发新生鼠肺损伤的影响。方法:选用新生Wistar乳鼠120只,随机分为空气对照组、高氧模型组、布地奈德联合特布他林(B+T)治疗组和PGE1治疗组4组,每组分为第3、7、14天3组,每组各10只。实验开始第3、7及14天处死每组动物,收取支气管肺泡灌洗液(BALF),采用硫代巴比妥酸法及考马斯亮蓝方法测定丙二醛(MDA)及总蛋白(TP)水平。采用HE染色法观察肺组织病理改变,免疫组织化学法测定肺组织中结缔组织生长因子(CTGF)、IFN-γ、TNF-α的表达强度。结果:①高氧模型组第3、7、14天BALF中MDA、TP的水平明显高于空气对照组,差异有统计学意义(P<0.05),B+T和PGE1组第3、7、14天BALF中MDA、TP的水平明显低于高氧模型组,差异有统计学意义(P<0.05),B+T治疗组与PGE1治疗组第3、7、14天BALF中MDA、TP的水平比较差异无统计学意义(P>0.05);②高氧模型组第3、7、14天肺组织中CTGF、IFN-γ、TNF-α的表达强度较空气对照组明显增高,差异有统计学意义(P<0.05),B+T治疗组、PGE1治疗组第3、7、14天肺组织中CTGF、IFN-γ、TNF-α的表达强度均明显低于高氧模型组,差异有统计学意义(P<0.05);③高氧模型组病理切片可见肺内小血管扩张充血、血管壁及小支气管壁水肿、间质内炎性细胞增多,纤维组织增生,肺泡间隔增宽,出现肺泡相融合、肺结构紊乱,而B+T治疗组和PGE1治疗组肺组织病理改变较高氧模型组明显减轻。结论:布地奈德联合特布他林和前列腺素E1对新生鼠高氧肺损伤具有保护作用,其作用机制可能与抑制氧自由基和细胞因子的释放有关。
Objective: To investigate the effect of inhalation of Budesonide combined with Terbutaline and inhalation of prostaglandin E1 (PGE1) on lung injury induced by hyperoxia in neonatal rats. Methods: One hundred and twenty newborn Wistar rats were randomly divided into 4 groups: air control group, hyperoxia model group, budesonide combined with terbutaline (B + T) group and PGE1 treatment group, each group was divided into 3 groups , 7 and 14 days in 3 groups, each group of 10. Each group of animals was sacrificed on the 3rd, 7th and 14th days after the start of the experiment, bronchoalveolar lavage fluid (BALF) was collected, and malondialdehyde (MDA) and total protein (TP) were measured by thiobarbituric acid method and Coomassie brilliant blue method Level. The pathological changes of lung tissue were observed by HE staining. The expression of connective tissue growth factor (CTGF), IFN-γ and TNF-α in lung tissue were detected by immunohistochemistry. Results: ① The levels of MDA and TP in BALF of the 3rd, 7th and 14th day in hyperoxia model group were significantly higher than those in the air control group (P <0.05) The levels of MDA and TP in BALF in 14 days were significantly lower than those in hyperoxia group (P <0.05). The contents of MDA and TP in BALF of B + T group and PGE1 group on days 3, 7 and 14 (P> 0.05). ②The expression of CTGF, IFN-γ and TNF-α in the lung tissue of the hyperoxia model group was significantly higher than that of the air control group on days 3, 7 and 14 (P <0.05). The expression of CTGF, IFN-γ and TNF-α in B + T group and PGE1 group on the 3rd, 7th and 14th day were significantly lower than those in the hyperoxia model group (P <0.05). (3) Pathological examination of hyperoxia model revealed small pulmonary dilation and congestion in the lung, edema of the vessel wall and small bronchial wall, increased inflammatory cells in the interstitium, proliferation of fibrous tissue and broadening of the alveolar septa Alveolar fusion, pulmonary structure disorders, and B + T treatment group and PGE1 treatment group lung tissue pathological changes than the hyperoxia model group was significantly reduced. CONCLUSION: Budesonide combined with terbutaline and prostaglandin E1 have a protective effect on hyperoxia-induced lung injury in neonatal rats, which may be related to the inhibition of the release of oxygen free radicals and cytokines.