乙酰辅酶A羧化酶调控Th17细胞分化参与哮喘气道炎症

发布时间：2018-10-19 20:05

【摘要】：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P0.001),DMSO对照组与哮喘组差异无统计学意义(P0.05),ACC抑制剂组较哮喘组显著下降(P0.001)。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P0.008],且DMSO对照组与哮喘组差异无统计学意义(P0.05),ACC抑制剂组显著低于哮喘组(P0.008)。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P0.008],DMSO对照组与哮喘组差异无统计学意义(P0.05),ACC抑制剂组较哮喘组显著降低(P0.008)。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。
[Abstract]:Objective to investigate the effect of acetyl coA carboxylase (ACC) on the differentiation of Th17 cells in acute asthmatic mice. Methods 24 female C57BL/6 mice were randomly divided into normal control group, asthma group, DMSO control group and ACC inhibitor group. Asthma group, DMSO control group and ACC inhibitor group were sensitized with ovalbumin (OVA) to induce acute asthma model. The normal control group should be treated with the same volume of phosphate buffer (PBS). The ACC inhibitor group was treated by intraperitoneal injection of ACC specific inhibitor TOFA solution (dissolved in DMSO, and diluted with PBS) twice a week, and the DMSO control group was treated with DMSO solution of the same concentration. The mice were killed 24 days later, lung tissue and serum samples were collected. The infiltration of inflammatory cells in lung tissue was observed by HE staining, the total IgE concentration was detected by ELISA method, and the percentage of Th17 cells in CD4~ T cells was detected by flow cytometry. Results the infiltration of inflammatory cells in lung tissue in asthmatic group, DMSO control group and ACC inhibitor group was significantly higher than that in normal control group (3.50 卤0.14 卤3.47 卤0.08 卤2.07 卤0.20 vs 0.50 卤0.17). There was no significant difference between P0.001), DMSO control group and asthma group (P0.05). The serum total IgE levels in asthma group, DMSO control group and ACC inhibitor group were significantly higher than those in normal control group [(5 680.40 卤831.40) ng/ml, (5 624.79 卤365.50) ng/ml vs (400.52 卤57.13) ng/ml, P 0.008], and there was no significant difference between DMSO control group and asthma group (P0.05).), ACC inhibitor group was significantly lower than asthma group (P0.008). The percentage of Th17 cells in lung tissue of asthma group, DMSO control group and ACC inhibitor group was significantly higher than that of normal control group [(2.01 卤0.12)%, (1.95 卤0.16)%, (0.82 卤0.04)% vs (0.59 卤0.03)%, P 0.008]. There was no significant difference between DMSO control group and asthma group (P0.05). Conclusion after inhibiting ACC, the airway inflammation induced by OVA in asthmatic mice was significantly alleviated, while the Th17 cells in lung tissue decreased, and the serum total IgE concentration decreased, suggesting that ACC may play a role in the pathogenesis of asthma by promoting the differentiation of Th17 cells.
【作者单位】： 武汉大学中南医院呼吸内科;
【基金】：国家自然科学基金(81072684)
【分类号】：R562.25

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