新生期肺炎链球菌肺炎对VA的影响及其与肺部免疫及气道反应性的关系研究

发布时间：2018-12-19 08:32

【摘要】：目的研究新生期肺炎链球菌肺炎(Streptococcus pneumoniaepneumonia,S.pp)对维生素A(VA)水平的影响及其与肺部免疫及气道反应性的关系。方法 Balb/c小鼠出生后第7天鼻腔滴注2×10~7CFU肺炎链球菌5μl建立新生期S.pp模型,对照组滴注等量PBS,新生期肺炎链球菌肺炎补充VA组(S.pp+VA)感染后口饲补充VA,每天1次,连续4天,对照组给予等量VA溶解溶质菜籽油。收集感染后第7、14、21、28天肺组织、血清、肝脏组织标本,高效液相色谱仪(HPLC)监测组织中VA水平。小鼠成年后肺组织病理切片HE染色观察肺组织病理改变,体积描记法检测小鼠肺功能,ELISA检测支气管肺泡灌洗液(BALF)上清IL-4、IL-5、IL-13、IL-17A、INF-γ水平,流式细胞术检测肺组织中的CD4+T细胞亚群Th1、Th2及Foxp3~+Treg。结果 S.pp组小鼠肺组织VA持续降低至感染后4周,血清VA降低直至感染后2周恢复正常,而肝脏中VA水平无统计学差异。S.pp+VA组肺组织炎性细胞浸润较S.pp组显著减轻,S.pp+VA组BALF中IL-4、IL-5、IL-13及IL-17A水平显著低于S.pp组(P0.05),IFN-γ则显著增高(P0.01),肺组织Th1、Foxp3~+Treg显著高于S.pp组(P0.01),Th2水平明显降低(P0.01),且Th1/Th2比值显著增高(5.7 vs 1.7,P0.001))。S.pp+VA组小鼠气道反应性显著低于S.pp组(P0.001)。结论新生期肺炎链球菌肺炎致肺部VA水平持续降低至成年期,肺炎后补充VA能减轻新生期肺炎链球菌肺炎后肺组织炎性细胞浸润,促进Foxp3~+Treg表达、纠正Th1/Th2失衡,抑制成年期气道高反应性形成。
[Abstract]:Objective to study the effect of streptococcus pneumoniae pneumonia (Streptococcus pneumoniaepneumonia,S.pp) on vitamin A (VA) and its relationship with lung immunity and airway responsiveness. Methods Balb/c mice were given 2 脳 10~7CFU Streptococcus pneumoniae 5 渭 l intranasal drip on the 7th day after birth to establish the neonatal S.pp model, while the control group was given the same amount of PBS, to supplement VA group (S.pp VA) with VA, orally after infection. Once a day for 4 days, the control group was given the same amount of VA dissolved rapeseed oil. Lung tissue, serum and liver tissue samples were collected on the 28th day after infection, and VA levels in tissues were monitored by high performance liquid chromatography (HPLC). The pathological changes of lung tissue were observed by HE staining in adult mouse lung tissue, lung function was detected by plethysmography, and IL-4,IL-5,IL-13,IL-17A,INF- 纬 level in (BALF) supernatant of bronchoalveolar lavage fluid was detected by ELISA. Detection of CD4 T cell subsets Th1,Th2 and Foxp3~ Treg. in lung tissue by flow cytometry Results in S.pp group, the VA in lung tissue decreased to 4 weeks after infection, and serum VA decreased until 2 weeks after infection. However, there was no significant difference in the level of VA in liver. The infiltration of inflammatory cells in lung tissue in S.pp VA group was significantly less than that in S.pp group, and the levels of IL-4,IL-5,IL-13 and IL-17A in BALF in S.pp VA group were significantly lower than those in S.pp group (P0.05). IFN- 纬 was significantly increased (P0.01), Th1,Foxp3~ Treg in lung tissue was significantly higher than that in S.pp group (P0.01), Th2 level was significantly decreased (P0.01), and Th1/Th2 ratio was significantly increased (5.7 vs 1.7). The airway reactivity of P0.001). S.pp VA group was significantly lower than that of S.pp group (P0. 001). Conclusion the level of VA in the lung of neonatal streptococcus pneumoniae decreased to adult stage. VA supplementation after pneumonia can alleviate the infiltration of inflammatory cells in lung tissue, promote the expression of Foxp3~ Treg and correct the imbalance of Th1/Th2 after neonatal streptococcus pneumoniae pneumonia. Inhibition of airway hyperresponsiveness in adults.
【作者单位】：儿童发育疾病研究省部共建教育部重点实验室儿科学重庆市重点实验室儿童发育重大疾病国际科技合作基地;重庆医科大学附属儿童医院呼吸科;
【基金】：国家自然科学基金面上项目(81270086) 重庆市科委重点项目(cstc2017jcyj B0160)
【分类号】：R725.6

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