目的 基于小分子RNA-155（miR-155）/细胞因子信号抑制因子1（SOCS1）轴研究积雪草苷对高氧致新生大鼠支气管肺发育不良的保护作用。方法 将新生大鼠随机分为对照组、模型组、积雪草苷低剂量（10 mg/kg）组、积雪草苷中剂量（25 mg/kg）组、积雪草苷高剂量（50 mg/kg）组、布地奈德（1.5 mg/kg）组，每组12只。除对照组外的其他各组在高浓度氧中暴露14 d建立新生大鼠支气管肺发育不良模型，同时以相应浓度积雪草苷对不同剂量积雪草苷组进行灌胃，布地奈德组行布地奈德雾化治疗。采用苏木精-伊红染色检测各组大鼠肺组织发育情况，测定放射状肺泡计数（RAC）、肺泡平均截距（MLI）；采用超氧化物歧化酶（SOD）及丙二醛（MDA）检测试剂盒分别检测肺组织SOD、MDA水平；采用酶联免疫吸附法检测血清中肿瘤坏死因子α（TNF-α）、白介素6（IL-6）水平；采用实时荧光定量PCR法检测各组大鼠肺组织中miR-155、SOCS1的mRNA水平；采用蛋白免疫印迹法检测各组大鼠肺组织中SOCS1蛋白的相对表达。结果 与对照组相比，模型组大鼠出现肺组织结构紊乱，肺泡融合增大，肺泡间隔不均，平均间隙增大，肺泡数量明显减少等肺发育不良症状，同时MLI、肺组织MDA水平、血清IL-6及TNF-α水平、肺组织miR-155水平均明显升高（P < 0.05），肺组织RAC、SOD水平、SOCS1 mRNA及蛋白水平均明显降低（P < 0.05）。与模型组相比，积雪草苷低、中、高剂量组、布地奈德组大鼠上述肺发育不良症状改善，MLI、肺组织MDA水平、血清IL-6及TNF-α水平、肺组织miR-155水平均降低（P < 0.05），肺组织RAC、SOD水平、SOCS1 mRNA及蛋白水平均升高（P < 0.05），且积雪草苷对肺发育不良症状及上述指标的改善程度有剂量依赖性（P < 0.05）。积雪草苷高剂量组与布地奈德组相比，上述指标差异均无统计学意义，且均达到对照组水平（P > 0.05）。结论 积雪草苷可减轻高氧导致的新生大鼠肺部炎症损伤，改善支气管肺发育不良症状，且存在剂量依赖性。其作用机制可能与下调miR-155表达、上调SOCS1表达有关。

Objective To study the protective effect of asiaticoside against hyperoxia-induced bronchopulmonary dysplasia in neonatal rats based on the microRNA-155 (miR-155)/suppressor of cytokine signaling-1 (SOCS1) axis. Methods Neonatal rats were randomly divided into a control group, a model group, a low-dose asiaticoside group (10 mg/kg), a middle-dose asiaticoside group (25 mg/kg), a high-dose asiaticoside group (50 mg/kg), and a budesonide group (1.5 mg/kg), with 12 rats in each group. All rats except those in the control group were exposed to a high concentration of oxygen for 14 days to establish a neonatal rat model of bronchopulmonary dysplasia. The low-, middle-, and high-dose asiaticoside groups were given asiaticoside at different doses by gavage, and those in the budesonide group were given budesonide aerosol treatment. Hematoxylin and eosin staining was used to observe lung tissue development and measure radial alveolar count (RAC) and mean linear intercept (MLI). Superoxide dismutase (SOD) and malondialdehyde (MDA) detection kits were used to measure the levels of SOD and MDA in lung tissue. ELISA was used to measure the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Quantitative real-time PCR was used to measure the mRNA expression of miR-155 and SOCS1 in lung tissue. Western blotting was used to measure the protein expression of SOCS1 in lung tissue. Results Compared with the control group, the model group had the symptoms of bronchopulmonary dysplasia such as a disordered structure of lung tissue, enlargement of alveolar fusion, uneven alveolar septa, enlargement of average alveolar space, and a reduction in alveolar number. The model group also had significant increases in MLI, MDA level in lung tissue, serum levels of IL-6 and TNF-α, and miR-155 level in lung tissue (P < 0.05) and significant reductions in RAC, SOD level, and mRNA and protein expression of SOCS1 in lung tissue (P < 0.05). Compared with the model group, the low-, middle-, and high-dose asiaticoside groups and the budesonide group had significant improvement in the above symptoms of bronchopulmonary dysplasia, significant reductions in MLI, MDA level in lung tissue, serum levels of IL-6 and TNF-α, and miR-155 level in lung tissue (P < 0.05), and significant increases in RAC, SOD level, and mRNA and protein expression of SOCS1 in lung tissue (P < 0.05). Asiaticoside improved the above symptoms and indices in a dose-dependent manner. There were no significant differences in the above indices between the high-dose asiaticoside and budesonide groups (P > 0.05). Conclusions Asiaticoside can alleviate inflammation injury induced by hyperoxia in neonatal rats and improve the symptoms of bronchopulmonary dysplasia in a dose-dependent manner, possibly by down-regulating the expression of miR-155 and up-regulating the expression of SOCS1.