匹多莫德对支原体感染小鼠肺功能损伤的影响及其机制研究

Effect of pidotimod on lung function impairment and the mechanism thereof in mice infected with Mycoplasma pneumoniae

目的观察匹多莫德对支原体感染(MPI)小鼠肺功能损伤的保护作用,并探讨其可能机制。方法MPI小鼠随机分为MPI组和实验A、B、C组,每组10只;另取10只健康小鼠设为正常组。实验A、B、C组分别灌胃匹多莫德颗粒100、200和400 mg/kg,正常组、MPI组灌胃等量生理盐水,1次/d,持续3 d。采用小动物呼吸机检测肺功能,紫外分光光度法和细胞色素C还原法检测血清氧化应激指标,酶联免疫吸附试验检测血清免疫指标,苏木精-伊红染色观察肺组织病理变化,Western blotting检测肺组织核因子E2相关因子2(Nrf2)、血红素加氧酶-1(HO-1)蛋白表达。结果与正常组比较,MPI组每分钟通气量(MV)、潮气量(TV)、最大呼气量(MEV)均减少(P<0.05),血清谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)活性、γ干扰素(IFN-γ)水平均降低(P<0.05),血清白细胞介素-4(IL-4)水平升高(P<0.05);与MPI组比较,实验A、B、C组MV、TV、MEV均增加(P<0.05),GSH-Px、SOD活性均增强(P<0.05),IFN-γ水平升高(P<0.05),IL-4水平降低(P<0.05);与实验A组比较,实验B、C组MV、TV、MEV均增加(P<0.05),GSH-Px、SOD活性均增强(P<0.05),IFN-γ水平升高(P<0.05),IL-4水平降低(P<0.05);与实验B组比较,实验C组MV、TV、MEV均增加(P<0.05),GSH-Px、SOD活性均增强(P<0.05),IFN-γ水平升高(P<0.05),IL-4水平降低(P<0.05)。与正常组比较,MPI组肺组织Nrf2、HO-1蛋白相对表达量均降低(P<0.05);与MPI组比较,实验A、B、C组肺组织Nrf2、HO-1蛋白相对表达量均升高(P<0.05);与实验A组比较,实验B、C组肺组织Nrf2、HO-1蛋白相对表达量均升高(P<0.05);与实验B组比较,实验C组肺组织Nrf2、HO-1蛋白相对表达量均升高(P<0.05)。结论匹多莫德可能通过调节Nrf2/HO-1信号通路,改善MPI小鼠肺功能和免疫功能,减轻氧化应激损伤。

Objective To observe the protective effect of pidotimod on lung function impairment in mice with Mycoplasma pneumoniae infection(MPI)and to explore the possible mechanism.Methods MPI mice were randomly divided into MPI group,experiment A group,experiment B group,and experiment C group,with 10 mice in each group.Besides,another 10 healthy mice were set as the normal group.The mice in experiment A,B,and C groups were given pidotimod granules(100,200,and 400 mg/kg,respectively)by gavage,and those in the normal group and the MPI group were given equal volumes of normal saline by gavage,once a day for 3 days.Lung function parameters were measured by a small animal ventilator.Serum oxidative stress indicators were detected via ultraviolet spectrophotometry and the cytochrome C assay,while serum immune indicators were detected via the enzyme-linked immunosorbent assay.The pathological changes were observed with the hematoxylin and eosin staining,and the protein expressions of nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)in lung tissues were measured via Western blotting.Results Compared with the normal group,the minute ventilation(MV),tidal volume(TV),and maximum expiratory volume(MEV)were lower(P<0.05),the activities of serum glutathione peroxidase(GSH-Px)and superoxide dismutase(SOD)as well as the serum level of interferon-γ(IFN-γ)were lower(P<0.05),and the serum level of IL-4 was higher in the MPI group(P<0.05).Compared with the MPI group,the MV,TV,and MEV were higher(P<0.05),the activities of GSH-Px and SOD were higher(P<0.05),the IFN-γlevel was higher(P<0.05),and the IL-4 level was lower in the experiment A,B and C groups(P<0.05).Compared with the experimental A group,the MV,TV,and MEV were higher(P<0.05),the activities of GSH-Px and SOD were higher(P<0.05),the IFN-γlevel was higher(P<0.05),and the IL-4 level was lower in the experimental B and C groups(P<0.05).Compared with the experimental B group,the MV,TV,and MEV were higher(P<0.05),the activities of GSH-Px and SOD were higher(P<0.05),the IFN-γlevel was higher(P<0.05),and the IL-4 level was lower in the experimental C group(P<0.05).Compared with the normal group,the protein expressions of Nrf2 and HO-1 in pulmonary tissues of the MPI group were lower(P<0.05).Compared with the MPI group,the protein expressions of Nrf2 and HO-1 in pulmonary tissues of the experimental A,B,and C groups were higher(P<0.05).Compared with the experimental A group,the protein expressions of Nrf2 and HO-1 in pulmonary tissues of the experimental B and C groups were higher(P<0.05).Compared with the experimental B group,the protein expressions of Nrf2 and HO-1 in pulmonary tissues of the experimental C group were higher(P<0.05).Conclusions Pidotimod may improve lung function and immune function,and reduce oxidative stress in mice with MPI by regulating the Nrf2/HO-1 signaling pathway.