發(fā)布時(shí)間：2018-12-19 08:32

【摘要】：目的研究新生期肺炎鏈球菌肺炎(Streptococcus pneumoniaepneumonia,S.pp)對(duì)維生素A(VA)水平的影響及其與肺部免疫及氣道反應(yīng)性的關(guān)系。方法 Balb/c小鼠出生后第7天鼻腔滴注2×10~7CFU肺炎鏈球菌5μl建立新生期S.pp模型,對(duì)照組滴注等量PBS,新生期肺炎鏈球菌肺炎補(bǔ)充VA組(S.pp+VA)感染后口飼補(bǔ)充VA,每天1次,連續(xù)4天,對(duì)照組給予等量VA溶解溶質(zhì)菜籽油。收集感染后第7、14、21、28天肺組織、血清、肝臟組織標(biāo)本,高效液相色譜儀(HPLC)監(jiān)測(cè)組織中VA水平。小鼠成年后肺組織病理切片HE染色觀察肺組織病理改變,體積描記法檢測(cè)小鼠肺功能,ELISA檢測(cè)支氣管肺泡灌洗液(BALF)上清IL-4、IL-5、IL-13、IL-17A、INF-γ水平,流式細(xì)胞術(shù)檢測(cè)肺組織中的CD4+T細(xì)胞亞群Th1、Th2及Foxp3~+Treg。結(jié)果 S.pp組小鼠肺組織VA持續(xù)降低至感染后4周,血清VA降低直至感染后2周恢復(fù)正常,而肝臟中VA水平無(wú)統(tǒng)計(jì)學(xué)差異。S.pp+VA組肺組織炎性細(xì)胞浸潤(rùn)較S.pp組顯著減輕,S.pp+VA組BALF中IL-4、IL-5、IL-13及IL-17A水平顯著低于S.pp組(P0.05),IFN-γ則顯著增高(P0.01),肺組織Th1、Foxp3~+Treg顯著高于S.pp組(P0.01),Th2水平明顯降低(P0.01),且Th1/Th2比值顯著增高(5.7 vs 1.7,P0.001))。S.pp+VA組小鼠氣道反應(yīng)性顯著低于S.pp組(P0.001)。結(jié)論新生期肺炎鏈球菌肺炎致肺部VA水平持續(xù)降低至成年期,肺炎后補(bǔ)充VA能減輕新生期肺炎鏈球菌肺炎后肺組織炎性細(xì)胞浸潤(rùn),促進(jìn)Foxp3~+Treg表達(dá)、糾正Th1/Th2失衡,抑制成年期氣道高反應(yīng)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- 緯 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- 緯 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.
【作者單位】： 兒童發(fā)育疾病研究省部共建教育部重點(diǎn)實(shí)驗(yàn)室 兒科學(xué)重慶市重點(diǎn)實(shí)驗(yàn)室 兒童發(fā)育重大疾病國(guó)際科技合作基地;重慶醫(yī)科大學(xué)附屬兒童醫(yī)院呼吸科;
【基金】：國(guó)家自然科學(xué)基金面上項(xiàng)目(81270086) 重慶市科委重點(diǎn)項(xiàng)目(cstc2017jcyj B0160)
【分類號(hào)】：R725.6

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