中国呼吸与危重监护杂志

中国呼吸与危重监护杂志

乙酰辅酶 A 羧化酶调控 Th17 细胞分化参与哮喘气道炎症

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目的观察乙酰辅酶 A 羧化酶(ACC)对 Th17 细胞分化的调控在急性哮喘小鼠模型发病机制中的作用。方法将 24 只雌性 C57BL/6 小鼠随机分为正常对照组、哮喘组、DMSO 对照组和 ACC 抑制剂组,每组 6 只。哮喘组、DMSO 对照组和 ACC 抑制剂组予以卵清蛋白(OVA)致敏、激发建立急性哮喘模型,正常对照组对应给予等体积的磷酸盐缓冲液(PBS)处理。其中 ACC 抑制剂组每周 2 次给予腹腔注射 ACC 特异性抑制剂 TOFA 溶液(先溶于 DMSO,后以 PBS 稀释)处理,DMSO 对照组对应给予等浓度 DMSO 溶液处理。24 d 后处死小鼠,收集肺组织和血清样本。肺组织 HE 染色观察小鼠肺组织炎性细胞浸润情况,ELISA 法检测血清总 IgE 浓度,流式细胞术检测肺组织 Th17 细胞在 CD4+ T 细胞中所占的百分率。结果哮喘组、DMSO 对照组、ACC 抑制剂组小鼠肺组织炎性细胞浸润均较正常对照组显著增加(3.50±0.14、3.47±0.08、2.07±0.20 比 0.50±0.17,均P<0.001),DMSO 对照组与哮喘组差异无统计学意义(P>0.05),ACC 抑制剂组较哮喘组显著下降(P<0.001)。哮喘组、DMSO 对照组、ACC 抑制剂组小鼠血清总 IgE 浓度均较正常对照组显著升高 [(5 680.40±831.40)ng/ml、(5 624.79±365.50)ng/ml、(2 028.95±134.60)ng/ml 比(400.52±57.13)ng/ml,均P<0.008],且 DMSO 对照组与哮喘组差异无统计学意义(P>0.05),ACC 抑制剂组显著低于哮喘组(P<0.008)。哮喘组、DMSO 对照组、ACC 抑制剂组小鼠肺组织 Th17 细胞在 CD4+ T 细胞中所占百分率均较正常对照组明显增高 [(2.01±0.12)%、(1.95±0.16)%、(0.82±0.04)% 比(0.59±0.03)%,均P<0.008],DMSO 对照组与哮喘组差异无统计学意义(P>0.05),ACC 抑制剂组较哮喘组显著降低(P<0.008)。结论抑制 ACC 后,OVA 诱导的哮喘小鼠气道炎症显著减轻,同时肺组织中 Th17 细胞减少,血清总 IgE 浓度下降,提示 ACC 可通过促进 Th17 细胞分化参与哮喘的发病。

ObjectiveTo investigate the role of acetyl CoA carboxylase (ACC)-induced Th17 development in the pathogenesis of asthma.MethodsA total of 24 C57BL/6 mice were randomly assigned to 4 groups (6 in each group), namely a normal group, an asthma group, a DMSO control group and an ACC inhibitor group. The mice in the asthma group, the DMSO control group and the ACC inhibitor group were sensitized and challenged with ovalbumin (OVA) to establish a model of acute asthma, the mice in the normal group were administrated with equal volume of phosphate buffered saline (PBS). The mice in the ACC inhibitor group were intraperitoneally administrated with TOFA, an ACC inhibitor (dissolved in DMSO firstly, then diluted with PBS solution) twice a week, while the DMSO control group were intraperitoneally administrated with equal concentration of DMSO. All mice were sacrificed 24 days later, then lung tissue and serum were collected. The inflammatory cells infiltrated in lung tissue were assessed by the means of HE staining under light microscope. The total level of IgE in serum was detected by ELISA. The percentage of Th17 cells in CD4+ T cells in lung tissue was evaluated by flow cytometry.ResultsThe inflammatory cells infiltration in the asthma group, the DMSO control group and the ACC inhibitor group increased significantly compared with that of the normal group (3.50±0.14, 3.47±0.08, 2.07±0.20vs. 0.50±0.17, allP<0.001), but there were no significant differences between the DMSO control group group and the asthma group (P>0.05), while administration of TOFA could significantly decrease the inflammatory cells infiltration (P<0.001). The total level of serum IgE in the asthma group, the DMSO control group and the ACC inhibitor group was significantly higher than that in the normal group [(5 680.40±831.40) ng/ml, (5 624.79±365.50) ng/ml, (2 028.95±134.60) g/mlvs. (400.52±57.13) ng/ml, allP<0.008], but there were no significant differences between the DMSO control group and the asthma group (P>0.05), while the total level of serum IgE in the ACC inhibitor group was significantly lower than that in the asthma group (P<0.008). The percentage of Th17 cells in CD4+ T cells in lung tissue increased markedly in the asthma group, the DMSO control group and the ACC inhibitor group compared with the normal group [(2.01±0.12)%, (1.95±0.16)%, (0.82±0.04)%vs. (0.59±0.03)%, bothP<0.008], and also there were no significant differences between the DMSO control group and the asthma group (P>0.05), while administration of TOFA could notably reduce the percentage of Th17 cells (P<0.008).ConclusionInhibition of ACC significantly alleviates the airway inflammation of OVA-induced asthma, and reduces the percentage of Th17 cells in lung tissue and the total level of serum IgE. ACC may participate in the pathogenesis of asthma by inducing Th17 development.

关键词: 哮喘; 乙酰辅酶 A 羧化酶; Th17 细胞; TOFA

Key words: Asthma; Acetyl CoA carboxylase; Th17 cells; TOFA

引用本文: 朱芳芳, 曹欢, 何光珍, 王译民, 陈毅斐, 杨炯, 高亚东. 乙酰辅酶 A 羧化酶调控 Th17 细胞分化参与哮喘气道炎症. 中国呼吸与危重监护杂志, 2017, 16(5): 500-504. doi: 10.7507/1671-6205.201703001 复制

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