Induction of airway remodeling and persistent cough by repeated citric acid exposure in a guinea pig cough model
在豚鼠咳嗽模型中反復檸檬酸暴露可引起氣道重塑和持續咳嗽
Shilei Cuia,b, Isao Itoa,?, Hitoshi Nakajia, Toshiyuki Iwataa, Hisako Matsumotoa, Tsuyoshi Ogumaa,
Tomoko Tajiria, Tadao Nagasakia, Yoshihiro Kanemitsua,c, Hiromi Izuharaa, Michiaki Mishimaa,Akio Niimia,c
a Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Japan
b Department of Respiratory Medicine, Huadong Hospital, Fudan University, Shanghai, China
c Department of Medical Oncology and Immunology, Nagoya City University, Graduate School of Medical Science, Japan
A B S T R A C T
Background:A previous study involving guinea pigs showed that repeated cough could increase peripheral airway smooth muscle area, which can also aggravate cough. The airway pathologic changes produced by prolonged cough are still unknown.
背景：先前一項涉及豚鼠的研究表明，反復咳嗽可增加外周氣道平滑肌面積，也可加重咳嗽。長期咳嗽引起的氣道病理改變尚不清楚。
Objective:To study the airway pathologic changes in prolonged cough models of guinea pigs.
目的：研究豚鼠長期咳嗽模型氣道病理變化。
Methods:Guinea pigs were assigned to three treatment groups: citric acid inhalation (CA) alone, citric acid inhalation with codeine pretreatment (COD), or saline solution inhalation (SA). Animals were challenged with citric acid or saline solution three times weekly. The intervention period was 22 or 43 days. Animals were challenged with citric acid on the first and last days of exposure. Lung specimens were obtained for pathologic analysis 72 h after the last exposure.
方法：將豚鼠分為3個治療組：單獨吸入檸檬酸(CA)、可待因預處理檸檬酸(COD)和鹽水吸入(SA)。每周用檸檬酸或鹽水對動物進行三次激發。干預期為22、43天。在暴露的天和后一天，用檸檬酸對動物進行挑戰。后一次暴露72h后取肺標本進行病理分析。
Results: Compared with the other two groups, the CA group had increased frequency of cough on both 22 and 43 days of exposure. Tracheal basement membrane (BM) thickness was increased after 43 days of exposure, correlating with the frequency of cough. The area of airway smooth muscles (ASM index) in small airways increased in the CA group after both 22 and 43 days of exposure, compared with the SA group. Compared with the COD group, the ASM index in small airways increased in the CA group after 22 days of exposure instead of 43 days of exposure.
結果：與其他兩組相比，CA組在暴露22天和43天時咳嗽頻率均增加。暴露43天后，氣管基膜(BM)厚度增加，與咳嗽頻率相關。暴露22和43天后，CA組氣道平滑肌面積(ASM指數)均較SA組增加。與COD組相比，CA組暴露22天后小氣道ASM指數升高，而非43天。
Conclusions:An increase in peripheral smooth muscle area by repeated cough was confirmed. Moreover, this is the first study to show that tracheal BM thickness increased after prolonged exposure (43 days). Repeated cough may lead to airway remodeling, which was also associated with an increased frequency of cough.
結論：反復咳嗽可增加外周平滑肌面積。此外，這是*研究表明，氣管骨厚度增加后，長期暴露(43天)。反復咳嗽可能導致氣道重塑，這也與咳嗽頻率增加有關。
Keywords:Cough、Cough reflex sensitivity、Airway remodeling、Mechanical stress
關鍵詞：咳嗽、咳嗽反射敏感性、氣道重塑、機械應激
