2022 年第 11 期 第 17 卷

益气固表丸对烟熏联合脂多糖诱导的慢性阻塞性肺疾病模型大鼠树突状细胞免疫功能的调节作用

Regulatory effect of Yiqi Gubiao pill on immune function of dendritic cell in model rats with chronic obstructive pulmonary disease induced by smoke combined with lipopolysaccharide

作者：荆晶李风森徐丹李争王晶姜敏罗建江

英文作者：Jing Jing Li Fengsen Xu Dan Li Zheng Wang Jing Jiang Min Luo Jianjiang

单位：新疆医科大学第四临床医学院新疆呼吸病研究实验室新疆医科大学附属中医医院呼吸科，乌鲁木齐830000

英文单位：Fourth Clinical Medical College of Xinjiang Medical University Xinjiang Laboratory Respiratory Disease Research Department of Respiratory Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University Urumqi 830000 China

关键词：慢性阻塞性肺疾病；益气固表丸；免疫功能；树突状细胞；模型大鼠

英文关键词：Chronicobstructivepulmonarydisease;YiqiGubiaopill;Immunefunction;Dendriticcell;Modelrats

• 摘要：

• 目的 研究益气固表丸对烟熏联合脂多糖诱导的慢性阻塞性肺疾病（COPD）模型大鼠树突状细胞(DC)免疫功能的调节作用。方法 将无特定病原体级雄性实验大鼠完全随机分为空白组、COPD组、COPD+地塞米松组和COPD+益气固表丸高、中、低剂量组，每组12只。除空白组外其余各组采用烟熏+脂多糖气管滴注方法建立COPD大鼠模型，造模成功后，空白组和COPD组给予0.9%氯化钠注射液灌胃，其余各组给予相应剂量的药物灌胃，2次/d，连续4周。比较各组大鼠灌胃后肺功能指标，比较各组大鼠外周血与肺泡灌洗液中趋化因子受体6（CCR6）、CCR7含量及肺组织中蛋白水平，观察各组大鼠肺组织形态学改变，免疫组织化学方法观察各组大鼠DC表达的变化。结果 与COPD组比较，益气固表丸干预组肺功能参数有所改善，且肺部病理学改变显示肺部结构损伤有所减轻。COPD+益气固表丸高剂量组外周血、肺泡灌洗液中CCR7含量明显高于COPD组［（1.07±0.32）μg/L比（0.65±0.09）μg/L、（1.07±0.33）μg/L比（0.71±0.10）μg/L］（均P<0.05）。COPD组CD80、CD86、OX62蛋白表达明显高于空白组，COPD+益气固表丸高剂量组CD86蛋白表达明显低于COPD+益气固表丸低剂量组，OX62表达明显低于COPD组（均P<0.05）；益气固表丸干预组随着剂量的递增，CD80、CD86、OX62表达有下降趋势。空白组大鼠OX62和主要组织相容性复合体Ⅱ阳性细胞广泛分布于肺泡、淋巴结周围，而COPD组大鼠OX62阳性细胞向肺实质中迁移聚集，益气固表丸不同剂量干预后该趋势逆转，逆转程度随剂量增加而明显。结论 益气固表丸可以明显降低COPD模型大鼠肺组织中趋化因子及共刺激分子的含量和表达，抑制未成熟DC的成熟，调节DC免疫功能，减轻COPD大鼠肺组织损伤，从而延缓疾病进展。

• Objective To study the regulatory effect of Yiqi Gubiao pill on immune function of dendritic cell(DC) in model rats with chronic obstructive pulmonary disease(COPD) induced by smoke combined with lipopolysaccharide. Methods Male experimental rats withont specific pathogens were randomly divided into blank group, COPD group, COPD+dexamethasone group, and COPD+Yiqi Gubiao pill high-dose, medium-dose and low-dose groups, with 12 rats in each group. COPD model rats were established by fumigation and lippolysaccharose intratracheal instillation except blank group. After modeling, blank group and COPD group were given 0.9% sodium chloride injection intragastric administration, and other groups were given corresponding dose of drug intragastric administration, twice a day, for consecutive 4 weeks. The lung function indexes of rats after intragastric administration were compared among the groups. Levels of C-C chemokine receptor 6 (CCR6) and CCR7 in peripheral blood and alveolar lavage fluid and the protein level in lung tissue were compared among the groups. The morphological changes of lung tissue of rats were observed, and the changes of DC expression were observed by immunohistochemistry. Results Compared with COPD group, the lung function parameters of Yiqi Gubiao pill intervention groups were improved, and the lung pathological changes showed that the structure injury was alleviated. The levels of CCR7 in peripheral blood and alveolar lavage fluid of COPD+Yiqi Gubiao pill high-dose group were significantly higher than that of COPD group［（1.07±0.32）μg/L vs （0.65±0.09）μg/L, （1.07±0.33）μg/L vs （0.71±0.10）μg/L］(all P<0.05). The expressiones of CD80, CD86 and OX62 protein of COPD group was significantly higher than those of blank group; the expression of CD86 protein of COPD+Yiqi Gubiao pill high-dose group was significantly lower than that of COPD+Yiqi Gubiao pill low-dose group, and the expression of OX62 was significantly lower than that of COPD group(all P<0.05); expressiones of CD80, CD86 and OX62 of Yiqi Gubiao pill intervention groups decreased with the increase of dosage. The OX62 and major histocompatibility complex Ⅱ positive cells of blank group were widely distributed around the alveoli and lymph nodes, while the OX62 positive cells of COPD group migrated to the lung parenchyma. After the intervention of different dosage of Yiqi Gubiao pill, the trend was reversed, and the degree of reversal was obvious with the increase of dosage. Conclusion Yiqi Gubiao pill can significantly reduce levels and expressiones of chemokines and costimulatory molecules in lung tissue of COPD model rats, inhibit the maturation of immature DC, regulate immune function of DC, reduce lung tissue injury of COPD rats, and delay the progression of the disease.