桔梗总皂苷通过抑制IRG-1对呼吸道合胞病毒肺炎小鼠治疗作用的研究

目的:探讨桔梗总皂苷通过抑制免疫反应基因1 (IRG-1)对呼吸道合胞病毒(RSV)肺炎小鼠的治疗作用。方法:将60只小鼠分为对照组、模型组、利巴韦林组和桔梗总皂苷低、中、高剂量组,每组10只。除对照组外,其余各组制备RSV肺炎小鼠模型。模型制备后第2天利巴韦林组按0.150 g/(kg·d)的剂量给予利巴韦林灌胃,桔梗总皂苷低、中、高剂量组依次按照0.014 g/(kg·d)、0.028 g/(kg·d)、0.056 g/(kg·d)的剂量给予桔梗总皂苷灌胃,对照组、模型组给予等体积生理盐水。连续给药5天,计算小鼠肺指数,进行病理学检查,检测支气管肺泡灌洗液中白细胞介素-6 (IL-6)、白细胞介素-1β(IL-1β)、活性氧(ROS)、肿瘤坏死因子-α(TNF-α)及血清中IRG-1 mRNA的含量。结果:对照组小鼠肺组织未见明显异常;模型组小鼠肺组织见肺泡壁增厚,支气管和细支气管周围有大量淋巴细胞浸润,腔内有大量脱落炎细胞及渗出物,存在肺实变表现;利巴韦林组小鼠肺组织病理改变与对照组接近;桔梗总皂苷各剂量组小鼠肺泡壁部分增厚,肺泡内炎症细胞渗出较模型组轻,呈剂量依赖性。与对照组比较,模型组小鼠肺指数、IL-6、IL-1β、TNF-α、ROS含量及血清中IRG-1 mRNA相对表达量均显著增高(P<0.05)。与模型组比较,利巴韦林组和桔梗总皂苷低、中、高剂量组小鼠肺指数、IL-6、IL-1β、TNF-α、ROS含量及血清中IRG-1 mRNA相对表达量均显著降低(P<0.05)。与利巴韦林组比较,桔梗总皂苷各剂量组小鼠肺指数、IL-6、IL-1β、TNF-α、ROS含量及血清中IRG-1 mRNA相对表达量均增高,除桔梗总皂苷高剂量组肺指数及TNF-α外,差异均有统讨学意义(P<0.05)。结论:桔梗总皂苷能改善RSV感染所致的小鼠肺炎炎症反应,其机制可能与抑制IRG-1的表达有关。

Effect Study on Total Saponins in Platycodi Radix for Mice with Respiratory Syncytial Virus Pneumonia via Inhibition of IRG-1

Objective: To discuss the therapeutic effect of total saponins in platycodi radix for mice with respiratory syncytial virus(RSV) pneumonia via inhibition of immune-response gene 1(IRG-1). Methods:Divided 60 mice into the control group,the model group,the ribavirin group and the groups of total saponins in platycodi radix of low,middle and high dose,10 mice in each group. Except the control group,other groups prepared the model of mice with RSV pneumonia. On the 2 nd day after model establishment,the ribavirin group was administered with ribavirin by gavage in 0.150 g/(kg·d),the groups of total saponins in platycodi radix of low,middle and high dose were administered with total saponins in platycodi radix by gavage in 0.014 g/(kg·d),0.028 g/(kg·d) and 0.056 g/(kg·d) respectively,and the control group and the model group were given the equivalent volume of saline. The medication lasted for five days continuously. Calculated the lung index of mice,performed the pathological examination,and detected the contents of interleukin-6(IL-6),interleukin-1β(IL-1β),reactive oxygen species(ROS) as well as tumor necrosis factor-α(TNF-α) in bronchoalveolar lavage fluid and IRG-1 mRNA in serum.Results: There was no obvious abnormality being found in lung tissues of mice in the control group. In the model group,there appeared alveolar wall thickening in lung tissue of mice,a large amount of lymphocytes infiltration around bronchi and bronchioles, a large number of exfoliated inflammatory cells and exudates in cavity and the manifestations of pulmonary consolidation. Pathological changes in lung tissue of mice in the ribavirin group were similar to those in the control group.There appeared partial alveolar wall thickening in the groups of total saponins in platycodi radix of each dose, and the exudation of inflammatory cells within alveoli was slighter than that in the model group in a dose-dependent manner.Comparing with the control group,the lung index,contents of IL-6,IL-1β,TNF-α and ROS and relative expression levels of IRG-1 and mRNA in serum of mice in the model group were all significantly increased(P<0.05). Comparing with the model group,the lung index,contents of IL-6,IL-1β,TNF-α and ROS and relative expression levels of IRG-1 and mRNA in serum of mice in the groups of total saponins in platycodi radix of each dose were all significantly decreased(P<0.05).Comparing with the ribavirin group,the lung index,contents of IL-6,IL-1β,TNF-α and ROS and relative expression levels of IRG-1 and mRNA in serum of mice in the groups of total saponins in platycodi radix of each dose were all significantly increased(P<0.05),except the lung index and contents of TNF-α.Conclusion:Total saponins in platycodi radix can improve inflammatory reactions induced by RSV infection in mice with pneumonia,and its mechanism may be related to inhibiting the expression of IRG-1.