肠道菌群失调促进小鼠肺树突状细胞成熟并增强TLR2和TLR4表达

Alterations in intestinal microflora balance induce maturity and increase the expressions of TLR2 and TLR4 of dendritic cells in mouse lung

目的观察卵清蛋白(OVA)雾化吸入激发对抗生素所致肠道菌群失调小鼠肺组织中树突状细胞(DC)成熟度和Toll样受体2(TLR2)、TLR4表达的影响。方法将64只3周龄雌性BALB/c小鼠随机分为4组,菌群失调组、菌群失调加激发组、激发组、对照组,每组16只。于实验第14天用流式细胞术检测肺组织中DC成熟度(MHC-Ⅱ类分子)及其膜表面TLR2、TLR4的表达水平,采用免疫组织化学法检测肺组织中转化生长因子β1(TGF-β1)、白细胞介素-6(IL-6)蛋白表达,ELISA检测支气管肺泡灌洗液(BALF)中TGF-β1、IL-6的产生水平。结果与对照组和激发组比较,菌群失调组及菌群失调加激发组小鼠肺组织中DC细胞膜表面MHC-Ⅱ类分子及TLR2、TLR4的表达均增加,但这些分子在上述2组中的表达无差异(P>0.05)。与其他3组比较,菌群失调加激发组小鼠肺组织及BALF中TGF-β1、IL-6水平增高。结论肠道菌群失调使肺部DC成熟度增高,TLR2、TLR4表达增强。

Objective To observe the effect of intestinal microflora imbalance caused by antibiotics on the maturity of dendritic cells （DCs） and the expressions of Toll-like receptor 2 （TLR2）, TLR4 on DCs in the lung of ovalbumin （OVA）- induced asthma mice. Methods Sixty-four 3-week-old female BALB/c mice were divided randomly into 4 groups, i.e. micro- biota imbalance group, microbiota imbalamce combined with OVA challenge group, OVA challenge group and control group, with sixteen mice in each group. On day 14, flow cytometry was adopted to measure the DC subtypes and maturity （ MHC- II molecules）, and the expressions of TLR2, TLR4 on DCs. The expressions of transforming growth factor--β1 （TGF-[51） and interleukin-6 （IL-6） in situ in lung were detected by immunohistochemical staining. The levels of TGF--β1 and IL-6 in bronchoalveolar lavage fluid （BALF） were examined by ELISA. Results Compared with control group and OVA challenge group, MHC- l] molecules and TLR2, TLR4 expressions on DCs in the lung increased in both microbiota imbalance combined with OVA challenge group and microbiota imbalance group, but they were not significantly different between the two groups / P 〉 0. 05）. Compared with the other three groups, microbiota imbalance combined with OVA challenge group showed the up-regulated expressions of TGF-β1 and IL-6 proteins in lung and BALF. Conclusion The alterations in intestinal microflora balance promoted the maturity of DCs and raised the expressions of TLR2 and TLR4 on DCs in mouse lung.