Kang Ji Young, Kim In Kyoung, Hur Jung, Kim Seok Chan, Lee Sook Young, Kwon Soon Seog, Kim Young Kyoon
Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Tuberc Respir Dis (Seoul). 2019 Jan;82(1):71-80. doi: 10.4046/trd.2018.0049.
Efficacy and safety of tiotropium bromide, a muscarinic receptor antagonist, in treatment of asthma have been reported. However, its effect on airway remodeling in chronic asthma of the elderly has not been clearly verified. The objective of this study was to investigate the effect of tiotropium and expression of muscarinic receptors as its related mechanism in an aged mouse model of chronic asthma with airway remodeling.
BALB/c female mice age 6 weeks, 9 and 15 months were sensitized and challenged with ovalbumin (OVA) for three months. Tiotropium bromide was administered during the challenge period. Airway hyperresponsiveness (AHR) and pulmonary inflammation were measured. Parameters of airway remodeling, and expression levels of M₂ and M₃ receptors were examined.
Total cell with eosinophils, increased in the OVA groups by age, was decreased significantly after treatment with tiotropium bromide, particularly in the age group of 15 months. AHR and levels of interleukin (IL)-4, IL-5, and IL-13 were decreased, after tiotropium administration. In old aged group of 9- and 15-months-treated groups, hydroxyproline contents and levels of α-smooth muscle actin were attenuated. Tiotropium enhanced the expression of M₂ but decreased expression of M₃ in all aged groups of OVA.
Tiotropium bromide had anti-inflammatory and anti-remodeling effects in an aged mouse model of chronic asthma. Its effects seemed to be partly mediated by modulating expression M₃ and M₂ muscarinic receptors. Tiotropium may be a beneficial treatment option for the elderly with airway remodeling of chronic asthma.
已报道毒蕈碱受体拮抗剂噻托溴铵治疗哮喘的有效性和安全性。然而，其对老年慢性哮喘气道重塑的影响尚未得到明确证实。本研究的目的是在伴有气道重塑的老年慢性哮喘小鼠模型中，研究噻托溴铵的作用及其相关机制——毒蕈碱受体的表达。
对6周龄、9月龄和15月龄的雌性BALB/c小鼠进行致敏，并给予卵清蛋白（OVA）激发3个月。在激发期给予噻托溴铵。检测气道高反应性（AHR）和肺部炎症。检查气道重塑参数以及M₂和M₃受体的表达水平。
OVA组中嗜酸性粒细胞总数随年龄增加，经噻托溴铵治疗后显著降低，尤其是在15月龄年龄组。给予噻托溴铵后，AHR以及白细胞介素（IL）-4、IL-5和IL-13水平降低。在9月龄和15月龄的老年治疗组中，羟脯氨酸含量和α-平滑肌肌动蛋白水平降低。噻托溴铵增强了所有OVA老年组中M₂的表达，但降低了M₃的表达。
噻托溴铵在老年慢性哮喘小鼠模型中具有抗炎和抗重塑作用。其作用似乎部分是通过调节M₃和M₂毒蕈碱受体的表达介导的。噻托溴铵可能是老年慢性哮喘气道重塑患者的一种有益治疗选择。
