桔梗总皂苷对支气管肺发育不良新生大鼠肺损伤的作用及机制研究

Effect and mechanism of Platycodon grandiflorum saponins on lung injury in neonatal rats with bronchopulmonary dysplasia

摘要:

目的 探讨桔梗总皂苷（PGS）对高氧致支气管肺发育不良（BPD）新生大鼠肺损伤及HGF/c-Met信号通路的影响。方法 将66只SD新生大鼠分为对照组、BPD组、地塞米松（TD）组及桔梗总皂苷低、中、高剂量组，每组11只。除对照组外，通过持续吸入高浓度氧（氧体积分数为90%）复制BPD模型。桔梗总皂苷低、中、高剂量组分别腹腔注射50 mg/kg、100 mg/kg、200 mg/kg 桔梗总皂苷，地塞米松组腹腔注射地塞米松 5 mg/kg，BPD组和对照组给予等量生理盐水。连续给药14 d后，检测各组大鼠肺组织湿重/干重（W/D）值，HE染色法观察各组大鼠肺组织病理变化，并进行肺组织辐射状肺泡计数（RAC），酶联免疫吸附试验（ELISA）检测各组大鼠肺组织中炎症因子白细胞介素-6（IL-6）、肿瘤坏死因子α（TNF-α）水平，Western blotting检测蛋白HGF、c-Met、p-c-Met在肺组织的表达。结果 与对照组相比，BPD组大鼠肺泡结构不完整，肺泡腔增大，肺泡间隔增厚，且出现炎症细胞浸润，新生大鼠肺组织W/D值，炎症因子IL-6、TNF-α水平，HGF、p-c-Met/c-Met蛋白表达升高（P <0.05），肺组织RAC降低（P <0.05）；与BPD组相比，地塞米松组、桔梗总皂苷低、中、高剂量组新生大鼠肺泡病理改变明显减轻，大鼠肺组织W/D值、炎症因子IL-6、TNF-α水平、HGF、p-c-Met/c-Met蛋白表达降低（P <0.05），肺组织RAC升高（P <0.05）。结论 桔梗总皂苷可减轻BPD新生大鼠肺损伤及肺组织炎症反应，可能与HGF/c-Met信号通路有关。

Abstract:

Objective To investigate the effects of total saponins of Platycodon grandiflorum (PGS) on lung injury and HGF/c-Met signaling pathway in neonatal rats with bronchopulmonary dysplasia (BPD) induced by hyperoxia.Methods The 66 SD rats were divided into: control (control) group, BPD group, dexamethasone (TD) group, PGS low, medium, and high dose groups, 11 in each group. Except for the Control group, the BPD model was constructed by continuous inhalation of hyperoxia. PGS low, medium and high dose groups were injected intraperitoneally with 50, 100, and 200 mg/kg PGS, the TD group was intraperitoneally injected with TD 5 mg/kg, and the BPD group and control group were given the same amount of saline. After 14 days of intervention, the wet/dry weight (W/D) value of the lung tissue of each group of rats was detected, the pathological changes in the lung tissues of rats were observe by HE staining method in each group, the radial alveolar count (RAC) in lung tissue was carried out, ELISA was used to detect the levels of inflammatory factors interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in the lung tissues of rats in each group, and the expressions of HGF, c-Met, and p-c-Met proteins expression were detected by Western blotting.Results Compared with the Control group, the BPD group had larger alveolar cavity with incomplete alveolar structure, the alveoli space was thickened, and inflammatory cell infiltration appeared. The W/D value, the expression levels of IL-6, TNF-α, the protein levels of HGF, and p-c-Met/c-Met in lung tissue of neonatal rats were significantly higher (P < 0.05), and the RAC in lung tissue was significantly lower (P < 0.05); Compared with the BPD group, the pathological changes of the neonatal rats in the TD group, PGS low, medium and high dose groups were significantly reduced, the W/D value, the expression levels of IL-6, TNF-α, the protein levels of HGF and p-c-Met/c-Met in lung tissue of neonatal rats were significantly lower (P < 0.05), and the RAC in lung tissue was significantly higher (P < 0.05).Conclusions Platycodon grandiflorum saponins can alleviate lung injury in neonatal rats with BPD, slow down the inflammatory response of lung tissue, which may be related to the HGF/c-Met signaling pathway.