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16 August 2019 : Animal Research  

Gastric Acid and Pepsin Work Together in Simulated Gastric Acid Inhalation Leading to Pulmonary Fibrosis in Rats

Shi Chen1ABCDEFG, HongYu Chen2ACDEF, Yue Cheng3BCD, Yu Wei1DEF, XianMei Zhou1CDEF, Tian Li4ACF, JiPing Zhu1ABDEFG*, Qian Wang1ABCF

DOI: 10.12659/MSM.915628

Med Sci Monit 2019; 25:6153-6164

Abstract

BACKGROUND: The clinical association between gastroesophageal reflux disease (GERD) and idiopathic pulmonary fibrosis (IPF) has been known for many years, but it is still unclear. The present study investigated the association between experimentally simulated aspiration and pulmonary fibrosis.

MATERIAL AND METHODS: A total of 120 male Sprague-Dawley rats were randomly divided into a negative control group, a bleomycin group, and 3 simulated aspiration groups. The bleomycin group was administered a one-time intratracheal injection of bleomycin, whereas the 3 simulated aspiration groups were treated either with an intratracheal instillation of gastric fluid combined with pepsin, with pepsin alone, or with hydrochloric acid, all twice a week, and the negative control group was administered normal saline twice a week. Lung tissues were collected to evaluate pathological changes and the mRNA expression levels of connective tissue growth factor (CTGF), type I collagen, and transforming growth factor.

RESULTS: The results demonstrated that the degree of fibrosis in the early stage was low in each of the 3 simulated aspiration groups, but gradually increased over time. The expression levels of the downstream factor of fibrosis, CTGF, and type I collagen also reflected this trend.

CONCLUSIONS: The study demonstrates that aspiration of gastric contents can cause pulmonary fibrosis, and mixed aspiration of pepsin and gastric fluid can accelerate this process. This study provides strong evidence in support of a potential association between human GERD and IPF.

Keywords: Fibrosis, Gastric Acid, Gastric Juice, Inhalation, Administration, Inhalation, Bleomycin, Cysteine-Rich Protein 61, Gastroesophageal Reflux, idiopathic pulmonary fibrosis, Lung, Pepsin A, Pulmonary Fibrosis, Transforming Growth Factors

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750