Chinese Journal of Tissue Engineering Research ›› 2023, Vol. 27 ›› Issue (6): 827-834.doi: 10.12307/2023.265
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Wang Min1, Yin Xiushan2, Wang Yingxi1, Zhang Yan1, Zhao Long1, Xia Shuyue1
Received:
2022-03-04
Accepted:
2022-04-29
Online:
2023-02-28
Published:
2022-08-11
Contact:
Xia Shuyue, MD, Chief physician, Department of Respiratory Medicine, Center Hospital Affiliated to Shenyang Medical College, Shenyang 110024, Liaoning Province, China
Zhao Long, Master, Chief physician, Department of Respiratory Medicine, Center Hospital Affiliated to Shenyang Medical College, Shenyang 110024, Liaoning Province, China
About author:
Wang Min, Master candidate, Department of Respiratory Medicine, Center Hospital Affiliated to Shenyang Medical College, Shenyang 110024, Liaoning Province, China
Supported by:
CLC Number:
Wang Min, Yin Xiushan, Wang Yingxi, Zhang Yan, Zhao Long, Xia Shuyue. Inhalation of bone marrow mesenchymal stem cells-derived exosomes alleviates inflammatory injury in chronic obstructive pulmonary disease[J]. Chinese Journal of Tissue Engineering Research, 2023, 27(6): 827-834.
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2.3 各组肺功能指标的变化 为验证大鼠慢阻肺模型是否建立成功,以及确定雾化形式的外泌体对肺功能的影响。使用小动物肺功能仪测试肺功能指标,与对照组比较,模型组FEV0.2、FEV0.3、FEV0.2/FVC、FEV0.3/FVC、FEF25%、FEF50%、FEF25_75%、PEF均显著性降低(P < 0.05),表明模型组肺功能出现严重损伤;与模型组比较,外泌体雾化低、中、高剂量组FEV0.2、FEV0.3、FEV0.2/FVC、FEV0.3/FVC、FEF25%、FEF50%、FEF25_75%均显著性升高(P < 0.05)及尾静脉注射组FEV0.3、FEV0.3/FVC、FEF25%、FEF50%、FEF25_75%均显著性升高(P < 0.05),表明外泌体治疗可以改善慢阻肺的肺功能;与外泌体尾静脉注射组相比,外泌体雾化低、中、高剂量组FEV0.2、FEV0.3、FEV0.2/FVC、FEV0.3/FVC均显著性升高(P < 0.05),表明雾化吸入外泌体对肺功能的改善程度强于尾静脉注射外泌体治疗,见表1。"
2.4 各组大鼠血清及支气管肺泡灌洗液中炎症因子水平 为明确雾化外泌体是否影响慢阻肺的炎症水平,通过ELISA实验对各组大鼠血清及肺泡灌洗液中的白细胞介素1β和肿瘤坏死因子α进行定量分析。结果显示,模型组大鼠血清和支气管肺泡灌洗液中白细胞介素1β及肿瘤坏死因子α水平明显高于对照组(P < 0.05)。与模型组相比,外泌体雾化低、中、高剂量组及外泌体尾静脉注射组大鼠血清和肺泡灌洗液中两种炎症因子水平均降低(P < 0.05)。低剂量外泌体雾化组大鼠血清和肺泡灌洗液中两种炎症因子水平显著低于外泌体雾化中、高剂量组和外泌体尾静脉注射组(P < 0.05),可见雾化形式的外泌体可减轻慢阻肺炎症反应,其中以低剂量外泌体雾化作用最为显著,见图4。"
2.5 各组肺组织病理学变化 为明确雾化外泌体对慢阻肺模型大鼠肺组织病理学的影响,进行了苏木精-伊红染色和Masson染色。苏木精-伊红染色结果显示,与对照组相比,经过反复的脂多糖和香烟烟雾刺激后的慢阻肺模型组大鼠存在明显的炎症细胞浸润,且炎症细胞多聚集在血管及支气管周围,支气管管腔内可见黏液性血栓,此外,还可观察到肺泡壁变薄过度扩张,部分可见肺泡融合。然而,与模型组相比,经低、中和高剂量外泌体雾化治疗后显著降低了气道炎症和肺泡结构的破坏,其中在低剂量外泌体雾化组中,大鼠肺组织的血管及支气管周围有少量的炎症细胞浸润,未见明显的支气管黏液栓,肺泡壁轻度扩张,且有少量的肺泡融合。尾静脉注射外泌体的治疗效果并不显著,见图5A。根据各组苏木精-伊红染色结果进行了大鼠肺组织炎症评分,见图5B。与对照组相比,模型组大鼠炎症评分明显升高(P < 0.05)。与模型组相比,外泌体雾化组炎症评分显著降低(P < 0.05),其中低剂量外泌体雾化组炎症评分明显低于外泌体尾静脉注射组(P < 0.05)。"
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