中文摘要：

目的 通过动物实验观察重组融合蛋白白细胞介素（IL）-17F/His对肺炎链球菌（SP）感染小鼠β-防御素-2（Defb2）、巨噬细胞炎性蛋白（MIP）及IL-4、IFN-γ等免疫相关炎性因子表达的影响,探讨重组融合蛋白IL-17F/His在体内防御SP感染的机制.方法 SPF级BALB/c小鼠随机分为SP感染组、重组融合蛋白干预组和正常对照组,以鼻腔黏膜接种方式建立SP感染模型,以鼻腔黏膜免疫方式进行重组蛋白免疫干预.采用实时荧光定量PCR法检测小鼠肺组织Defb2、MIP-1α和MIP-2β mRNA表达,酶联免疫吸附法测定小鼠肺泡灌洗液（BALF）、脾细胞和纵隔淋巴结细胞培养上清中MIP-1 α、MIP-2β、IL-4及IFN-γ水平,计数BALF中白细胞总数及分类,涂板培养行菌落计数,并对小鼠肺组织行免疫组织化学分析.结果 1.SP感染组小鼠BALF中白细胞总数158.50 ±22.27,中性粒细胞[（5.25±0.42）×106/L]、巨噬细胞[（149.00 ±21.09）×106/L]、淋巴细胞[（3.33±1.77）×106/L]计数均明显高于正常对照组[113.33±15.93、（2.33±0.82） ×106/L、（109.00 ±16.10）×106/L、（2.00 ±0.89）×106/L]（U/F=38.097、28.854、32.942、27.810,P均＜0.05）.与SP感染组比较,重组融合蛋白干预组小鼠BALF中SP的定植密度[2.75（1.15～3.09）×103/L]明显降低（P=0.002）,白细胞总数（209.00±18.23）及中性粒细胞[（8.67 ±2.16）×106/L]、巨噬细胞[（193.50±16.50）×106/L]、淋巴细胞[（6.83±1.17） ×106/L]计数均明显升高（U/F=38.097、28.854、32.942、27.810,P均＜0.05）.2.与SP感染组比较,重组融合蛋白干预组小鼠肺组织中Defb2 mRNA表达水平（31.64±4.97）和MIP-1α mRNA表达水平（5.81±1.09）均明显升高,MIP-2β mRNA表达水平（6.69 ±2.05）明显降低（t=4.889、2.306、3.536,P均＜0.05）.3.SP感染后小鼠BALF中MIP-1α、MIP-2β、IL-4、IFN-γ水平[（109.99±22.71）ng/L、（228.23 ±29.08）ng/L、（80.55±5.67） ng/L、（93.36 ±8.88） ng/L]均升?

英文摘要：

Objective To evaluate the effects of recombinant fusion protein interleukin-17F/His （IL-17F/His） on expression of immune-related inflammatory factors in murine models with Streptococcus pneumoniae （SP） infection.Methods BALB/c mice were randomly divided into SP infection group,fusion protein intervention group and the normal control group.Before intranasal infection with SP,the mice were treated with PBS or IL-17F/His respectively.The number of bacteria and leukocytes in bronchoalveolar lavage fluid （BALF） was counted,and the mRNA levels of β-defensin-2 （Defb2）,macrophage inflammatory protein （MIP）-lα and MIP-2β in lung tissue were detected by real-time fluorescent quantitative PCR,the concentrations of MIP-1 α,MIP-2β,IFN-γ and IL-4 in BALF,supematants of spleen cell and mediastinal lymph node cell were assayed by enzyme linked immunosorbent assay.The expressions of IL-17F and Defb2 in lung tissues were observed with immunocytochemistry.Results 1.Compared with the SP infection group,in the fusion protein intervention group,the total number of WBC （209.00 ± 18.23） was higher,the number of neutrophil,macrophage and lymphocyte[（8.67 ±2.16） × 106/L,（193.50 ± 16.50） × 106/L,（6.83 ± 1.17） × 106/L] were higher in BALF（U/F =38.097,28.854,32.942,27.810,all P ＜ 0.05）,while the number of bacteria [2.75 （1.15-3.09） × 103/L] was significantly lower（P =0.02）.2.Compared with SP infection group,the expression levels of Defb2 mRNA and MIP-1α mRNA（31.64 ±4.97,5.81 ± 1.09） in lung tissues were higher in the fusion protein intervention group,while the expression level of MIP-2β mRNA （6.69 ± 2.05） was lower （t =4.889,2.306,3.536,all P ＜ 0.05）.3.Compared with the SP infection group,the concentration of MIP-2β [（64.15 ± 13.41） ng/L] was significantly decreased and concentration of IL-4 [（92.28 ± 4.52） ng/L] was significantly increased in BALF in the fusion protein intervention group（H/F =159,289,40.767,all P ＜0.01）.4.Compared with the SP