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、(2028.95±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。 Objective To investigate the role of acetyl CoA carboxylase (ACC) in the regulation of Th17 cell differentiation in the pathogenesis of acute asthma in a mouse model. Methods Twenty-four female C57BL / 6 mice were randomly divided into normal control group, asthma group, DMSO control group and ACC inhibitor group, with 6 rats in each group. The asthmatic group, the DMSO control group and the ACC inhibitor group were sensitized with ovalbumin (OVA) to establish the acute asthmatic model. The normal control group was treated with equal volume of phosphate buffered saline (PBS). The ACC inhibitor group was intraperitoneally injected with ACC-specific inhibitor TOFA solution (first dissolved in DMSO and then diluted with PBS) twice a week, and the DMSO control group was treated with the same concentration of DMSO solution. Mice were sacrificed 24 days later and lung tissue and serum samples were collected. The inflammatory cell infiltration in the lung tissue of mice was observed by HE staining. The total serum IgE concentration was measured by ELISA. The percentage of Th17 cells in CD4 ~ + T cells in lung tissue was detected by flow cytometry. Results Compared with the normal control group, inflammatory cell infiltration in the asthmatic group, DMSO control group and ACC inhibitor group was significantly increased (3.50 ± 0.14, 3.47 ± 0.08, 2.07 ± 0.20, 0.50 ± 0.17, P <0.001, respectively) DMSO control group and asthma group was no significant difference (P> 0.05), ACC inhibitor group significantly decreased compared with asthma group (P <0.001). Serum total IgE levels in asthmatic group, DMSO control group and ACC inhibitor group were significantly higher than those in normal control group [(5 680.4 ± 831.40) ng / ml, (5624.79 ± 365.50) ng / ml, (2028.95 ± 134.60 ) (P <0.05), and there was no significant difference between the DMSO control group and the asthma group (P> 0.05). The levels of ACC inhibitor in the ACC inhibitor group were significantly lower than those in the asthma group (P < 0.008). The percentages of Th17 cells in CD4 ~ + T cells in asthmatic group, DMSO control group and ACC inhibitor group were significantly higher than those in normal control group [(2.01 ± 0.12)%, (1.95 ± 0.16)%, ( 0.82 ± 0.04)% (0.59 ± 0.03)%, respectively, P <0.008]. There was no significant difference between DMSO control group and asthma group (P> 0.05) . Conclusions After ACC inhibition, the airway inflammation of OVA-induced asthmatic mice was significantly reduced. Meanwhile, the decrease of Th17 cells and the decrease of total serum IgE in lung tissue suggested that ACC may participate in the pathogenesis of asthma by promoting the differentiation of Th17 cells.