虎杖调控脂质代谢治疗呼吸道合胞病毒感染肺纤维化小鼠模型的研究

Study on Lipid Metabolism Regulated by Polygonum Cuspidatum in the Treatment of Pulmonary Fibrosis Model of Respiratory Syncytial Virus Infection in Mice

  • 摘要:
      目的  研究虎杖对呼吸道合胞病毒(Respiratory syncytial virus, RSV)感染的肺纤维化小鼠肺组织脂质代谢及炎症过程的影响。
      方法  采用50 μL RSV病毒液(4×106 PFU · mL-1)联合博来霉素(Bleomycin, 2 mg · mL-1)气管滴注C57BL/6雄性小鼠, 建立RSV感染肺纤维化小鼠模型, 小鼠随机分为空白组、博来霉素诱导肺纤维化组、RSV感染肺纤维化组、虎杖(4.55 g · kg-1 · d-1)治疗组。造模第21天后采集各组小鼠的肺组织, 观察其病理改变及检测白细胞介素(IL)-6、肿瘤坏死因子(TNF)-α等炎症因子水平, 同时采用超高效液相色谱-四极杆-静电场轨道阱高分辨质谱联用(UPLC-Q Exactive Orbitrap/MS)技术进行脂质组学分析。
      结果  与空白组相比, 博来霉素诱导肺纤维化组和RSV感染肺纤维化组肺组织病理可见明显胶原纤维沉积及炎症浸润, 伴肺部炎症因子如IL-6、TNF-α水平显著升高(P < 0.05)。与博来霉素诱导肺纤维化组相比, RSV感染肺纤维化组呈现显著脂质代谢异常(P < 0.05), 具体表现为神经酰胺(Cer)、磷脂酰胆碱(PC)、磷脂酰乙醇胺(PE)、磷脂酰肌醇(PI)、酰基乙醇胺(NAE)、鞘磷脂(SM)、甘油二酯(DG)、甘油三酯(TG)、心磷脂(CL)、脂肪酸(FA)等脂质代谢紊乱。经虎杖(4.55 g · kg-1 · d-1)干预后, 上述指标均呈现显著回调趋势。
      结论  RSV可加重肺纤维化进程, 虎杖通过调控脂质代谢, 减轻RSV感染肺纤维化小鼠的肺组织炎症反应和胶原沉积, 改善小鼠肺组织纤维化进程。

     

    Abstract:
      OBJECTIVE  To investigate the effects of Polygonum Cuspidatum in the treatment of lung fibrosis mice infected with the respiratory syncytial virus (RSV) in terms of altered lipids and the inflammatory process in the lung.
      METHODS  C57BL/6 mice were given a tracheal drip of 50 μL RSV venom (4×106 PFU·mL-1) combined with bleomycin (2 mg·mL-1). The mice were randomly divided into blank group, bleomycin induced pulmonary fibrosis group, RSV infected pulmonary fibrosis group and Polygonum Cuspidatum (4.55 g·kg-1·d-1) treatment group. To assess changes in pathological and pro-inflammatory cytokine levels (IL-6, and TNF-α), lung tissues from each group were removed 21 days after modeling. Lipidomics analysis was then completed using UPLC-Q Exactive Orbitrap/MS.
      RESULTS  In comparison to the blank group, the lungs of the bleomycin induced pulmonary fibrosis group and RSV infected pulmonary fibrosis group showed prominent collagen fiber deposition and inflammatory infiltration, and the levels of lung inflammatory factors like IL-6 and TNF-α were noticeably higher (P < 0.05). The lipid metabolism of the RSV infected pulmonary fibrosis group differed significantly from that of the bleomycin induced pulmonary fibrosis group, with abnormal levels of ceramide (Cer), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), acylethanolamine (NAE), sphingomyelin (SM), diglyceride (DG), triglyceride (TG) and fatty acid (FA). The above indexes showed a significant trend of correction after the intervention of Polygonum Cuspidatum (4.55 g·kg-1·d-1).
      CONCLUSION  RSV has the potential to accelerate the progression of pulmonary fibrosis. Polygonum Cuspidatum reduces inflammation and collagen deposition in the lung tissue of RSV-infected mice with pulmonary fibrosis by regulating lipid metabolism, and it slows the progression of pulmonary fibrosis in mice.

     

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