糖皮质激素对高氧诱导的新生小鼠肺功能损伤、炎症反应和JAK2/STAT5通路的影响

Effects of Glucocorticoid on Pulmonary Function Damage,Inflammatory Response and JAK2/STAT5 Pathway in Neonatal Mice Induced by Hyperoxia

目的探究糖皮质激素(Glucocorticoid,Gluc)对高氧诱导的新生小鼠肺功能损伤、炎症反应和JAK2/STAT5通路的影响,为治疗肺功能损伤提供理论依据。方法构建肺损伤小鼠模型,将小鼠随机分为:对照组、Hyperoxia组、低剂量Gluc组、中剂量Gluc组、高剂量Gluc组。通过动物肺功能分析系统检测静息通气量、气道阻力、气道压力、肺容积、最大吸气流量。HE染色和TUNEL染色观察小鼠肺脏组织形态和细胞凋亡情况;RT-PCR、Western Blot检测α-SMA、TGF-β表达量;Elisa检测IL-6、MCP-1、iNOS含量;Western Blot检测JAK2、STAT5的磷酸化情况。结果与对照组相比,Hyperoxia组小鼠静息通气量、气道阻力、气道压力、肺容积、最大吸气流量显著降低(P<0.05),细胞凋亡数、α-SMA与TGF-β表达量、EOS比值、IL-6、MCP-1、iNOS含量均显著增加(P<0.05),且JAK2、STAT5磷酸化水平显著升高(P<0.05)。而中、高剂量Gluc可显著逆转高氧对小鼠以上指标的影响。此外,Hyperoxia组小鼠出现肺实质结构紊乱、肺泡间隔增宽等组织形态的改变,在低、中、高剂量Gluc组中组织形态改变程度逐渐降低。结论糖皮质激素可缓解肺组织损伤并下调模型小鼠肺脏组织中炎症因子含量,同时抑制JAK2/STAT5通路活性,对高氧诱导的肺组织损伤具有较好的治疗作用。

Objective To explore the effects of glucocorticoid(Gluc)on pulmonary function injury,inflammatory response and JAK2/STAT5 pathway in neonatal mice induced by hyperoxia,and to provide theoretical basis for the treatment of pulmonary function injury.Method The mice were randomly divided into control group,hyperoxia group,low dose Gluc group,medium dose Gluc group and high dose Gluc group.The ventilation volume,airway resistance,airway pressure,lung volume and maximal inspiratory flow were measured by animal pulmonary function analysis system.HE staining and TUNEL staining were used to observe the lung tissue morphology and cell apoptosis in mice;RT-PCR,Western Blot were used to detect the expression ofα-SMA and TGF-β;Elisa was used to detect the contents of IL-6,MCP-1 and i NOS;Western Blot was used to detect the phosphorylation of JAK2 and STAT5.Result Compared with the control group,the resting ventilation volume,airway resistance,airway pressure,lung volume and maximal inspiratory flow of hyperoxia group mice were significantly decreased(P<0.05).Apoptotic number,expression ofα-SMA and TGF-β,EOS ratio,IL-6,MCP-1 and i NOS contents were significantly increased(P<0.05),and JAK2,STAT5 phosphorylation levels were significantly increased(P<0.05).However,medium and high doses of Gluc could significantly reverse the effects of hyperoxia on the above indexes in mice.In addition,hyperoxia group mice showed structural disorders of pulmonary parenchyma,enlarged alveolar septum and other morphological changes.In low,medium and high dose Glucuc group,the degree of tissue morphological changes gradually decreased.Conclusion Glucocorticoids can also alleviate lung tissue injury and down-regulate the content of inflammatory factors in lung tissue of model mice,and inhibit JAK2/STAT5 pathway activity,which has a good therapeutic effect on hyperoxia-induced lung tissue injury.