Lei Yuan, Kuang Shou-Jin, Liao Cai-Shi
Department of Pediatrics, Third Xiangya Hospital, Central South University, Changsha 410013, China.
Zhongguo Dang Dai Er Ke Za Zhi. 2018 Jun;20(6):514-518. doi: 10.7499/j.issn.1008-8830.2018.06.016.
To observe the effects of bacterial lysates (OM-85BV) and all trans-retinoic acid (ATRA) on airway inflammation in asthmatic mice, and to investigate the immunoregulatory mechanism of OM-85BV and ATRA for airway inflammation in asthmatic mice.
Forty female BALB/c mice were randomly divided into five groups: normal control, model, OM-85BV, ATRA, and OM-85BV+ATRA. A bronchial asthma model was established by intraperitoneal injection of ovalbumin (OVA) for sensitization and aerosol challenge in all mice except those in the normal control group. On days 25-34, before aerosol challenge, the model, OM-85BV, ATRA, and OM-85BV+ATRA groups were given normal saline, OM-85BV, ATRA, and OM-85BV+ATRA respectively by gavage. Normal saline was used instead for sensitization, challenge, and pretreatment before challenge in the normal control group. These mice were anesthetized and dissected at 24-48 hours after the final challenge. Bronchoalveolar lavage fluid (BALF) was collected from the right lung to measure the levels of interleukin-10 (IL-10) and interleukin-17 (IL-17) by ELISA. The left lung was collected to observe histopathological changes by hematoxylin-eosin staining. The relative expression of ROR-γT mRNA was measured by quantitative real-time PCR.
Compared with the normal control group, the model group showed contraction of the bronchial cavity, increased bronchial secretions, and a large number of infiltrating inflammatory cells around the bronchi and alveolar walls, as well as a significantly reduced level of IL-10 (P<0.05) and significantly increased levels of IL-17 and ROR-γT mRNA (P<0.05). Compared with the model group, the OM-85BV, ATRA, and OM-85BV+ATRA groups showed a significant reduction in infiltrating inflammatory cells around the bronchi and alveolar walls; the OM-85BV group showed a significant increase in the level of IL-10 in BALF (P<0.05) and significant reductions in the levels of IL-17 and ROR-γT mRNA (P<0.05); the ATRA group showed significant reductions in the levels of IL-17 and ROR-γT mRNA (P<0.05). Compared with the OM-85BV group, the OM-85BV+ATRA group had significantly increased relative expression of ROR-γT mRNA (P<0.05). Compared with the ATRA group, the OM-85BV+ATRA group had significantly increased levels of IL-10 and IL-17 in BALF (P<0.05).
Both OM-85BV and ATRA can reduce respiratory inflammation in asthmatic mice. However, a combination of the two drugs does not have a better effect than them used alone.
观察细菌溶解产物（OM - 85BV）和全反式维甲酸（ATRA）对哮喘小鼠气道炎症的影响，并探讨OM - 85BV和ATRA对哮喘小鼠气道炎症的免疫调节机制。
40只雌性BALB/c小鼠随机分为五组：正常对照组、模型组、OM - 85BV组、ATRA组和OM - 85BV + ATRA组。除正常对照组外，其余小鼠均通过腹腔注射卵清蛋白（OVA）致敏，雾化激发建立支气管哮喘模型。在第25 - 34天，雾化激发前，模型组、OM - 85BV组、ATRA组和OM - 85BV + ATRA组分别通过灌胃给予生理盐水、OM - 85BV、ATRA和OM - 85BV + ATRA。正常对照组在致敏、激发及激发前预处理时均用生理盐水代替。末次激发后24 - 48小时将小鼠麻醉并处死。收集右肺支气管肺泡灌洗液（BALF），采用酶联免疫吸附测定（ELISA）法检测白细胞介素 - 10（IL - 10）和白细胞介素 - 17（IL - 17）水平。取左肺，采用苏木精 - 伊红染色观察组织病理学变化。采用实时定量聚合酶链反应（PCR）检测ROR - γT mRNA的相对表达量。
与正常对照组相比，模型组支气管腔收缩，支气管分泌物增多，支气管和肺泡壁周围有大量炎性细胞浸润，IL - 10水平显著降低（P < 0.05），IL - 17和ROR - γT mRNA水平显著升高（P < 0.05）。与模型组相比，OM - 85BV组、ATRA组和OM - 85BV + ATRA组支气管和肺泡壁周围浸润的炎性细胞显著减少；OM - 85BV组BALF中IL - 10水平显著升高（P < 0.05），IL - 17和ROR - γT mRNA水平显著降低（P < 0.05）；ATRA组IL - 17和ROR - γT mRNA水平显著降低（P < 0.05）。与OM - 85BV组相比，OM - 85BV + ATRA组ROR - γT mRNA相对表达量显著升高（P < 0.05）。与ATRA组相比，OM - 85BV + ATRA组BALF中IL - 10和IL - 17水平显著升高（P < 0.05）。
OM - 85BV和ATRA均可减轻哮喘小鼠的呼吸道炎症。然而，两种药物联合使用并不比单独使用效果更好。
