化湿败毒颗粒治疗呼吸道合胞病毒肺炎模型小鼠的脂质组学研究

Lipidomics Study of Huashi Baidu Granules in the Treatment of Respiratory Syncytial Virus Pneumonia Model Mice

目的探究化湿败毒颗粒对呼吸道合胞病毒(Respiratory syncytial virus,RSV)肺炎模型小鼠的治疗作用以及对肺组织脂质代谢的影响。方法将BALB/c小鼠随机分为空白组、模型组、利巴韦林组、地塞米松组、化湿败毒颗粒低剂量组和化湿败毒颗粒高剂量组。分别采集各组小鼠肺组织样本,观察其病理改变,检测肺组织中RSV-F、RSV-G、IL-1β、IL-6、TNF-αmRNA表达水平。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)技术对肺组织进行脂质组学分析,寻找脂质代谢变化。结果与空白组相比,模型组小鼠肺组织出现肺间质增厚,可见明显炎症浸润。肺组织病毒载量及肺部炎症因子如IL-1β、TNF-αmRNA水平显著升高(P<0.001)。同时,与空白组相比,模型组呈现脂质代谢的明显异常,具体表现为磷脂酰丝氨酸(PS)、磷脂酰甘油(PG)、鞘磷脂(SM)、神经酰胺(Cer)、甘油三酯(TG)、甘油二酯(DG)、脂肪酸(FA)、醚磷脂酰胆碱(PC O)、醚溶血磷脂酰胆碱(LPC O)等脂质代谢紊乱。经化湿败毒颗粒(25.12 g·kg^(-1)·d^(-1))干预可以调节上述脂质紊乱。结论化湿败毒颗粒可以通过调控脂质代谢,降低RSV感染小鼠肺组织中的病毒载量,减轻炎症反应等途径治疗RSV肺炎。

OBJECTIVE To investigate the therapeutic effect of Huashi Baidu Granules on respiratory syncytial virus(RSV)pneumonia model mice and its effect on lung lipid metabolism.METHODS BALB/c mice were randomly divided into control group,model group,Ribavirin group,Dexamethasone group,low dose group of Huashi Baidu Granules and high dose group of Huashi Baidu Granules.Lung tissue samples of mice in each group were collected to observe pathological changes and detect mRNA expression levels of RSV-F,RSV-G,IL-1β,IL-6 and TNF-αgenes.The lipid components of lung tissue were extracted and analyzed by ultra-high performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry(UPLC-Q Exactive Orbitrap MS)to find the changes in lipid metabolism.RESULTS The model group exhibited pulmonary interstitial thickening and inflammatory infiltration compared to the control group,the mRNA levels of viral load and inflammatory factors in lung tissue such as IL-1βand TNF-αwere significantly increased(P<0.001).Moreover,the model group exhibited significant abnormalities in lipid metabolism,including disorders in phosphatidylserine(PS),phosphatidylglycerol(PG),sphingomyelin(SM),ceramide(Cer),triglyceride(TG),diglyceride(DG),fatty acid(FA),ether phosphatidylcholine(PC O),ether lysophosphatidylcholine(LPC O).However,after the treatment of Huashi Baidu Granules(25.12 g·kg^(-1)·d^(-1)),the above indexes showed a significant improvement.CONCLUSION Huashi Baidu Granules can treat RSV pneumonia by regulating lipid metabolism,reducing viral load and alleviating inflammatory response in lung tissue.