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[细菌裂解物和全反式维甲酸对哮喘小鼠气道炎症的影响]

[Effects of bacterial lysates and all trans-retinoic acid on airway inflammation in asthmatic mice].

作者信息

Lei Yuan, Kuang Shou-Jin, Liao Cai-Shi

机构信息

Department of Pediatrics, Third Xiangya Hospital, Central South University, Changsha 410013, China.

出版信息

Zhongguo Dang Dai Er Ke Za Zhi. 2018 Jun;20(6):514-518. doi: 10.7499/j.issn.1008-8830.2018.06.016.

Abstract

OBJECTIVE

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.

METHODS

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.

RESULTS

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).

CONCLUSIONS

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.

摘要

目的

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。

方法

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。

结果

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)。

结论

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。

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