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A Novel Rat Model to Determine Interaction between Reflux Esophagitis and Bronchial Asthma
  1. Takashi Sugawa (sugawa{at}med.osaka-cu.ac.jp)
  1. Department of Gastroenterology, Osaka City University, Graduate School of Medicine, Japan
    1. Yasuhiro Fujiwara (yasu{at}med.osaka-cu.ac.jp)
    1. Department of Gastroenterology, Osaka City University, Graduate School of Medicine, Japan
      1. Hirokazu Yamagami (yamagami{at}msic.med.osaka-cu.ac.jp)
      1. Department of Gastroenterology, Osaka City University, Graduate School of Medicine, Japan
        1. Kenji Watanabe (kenjiw{at}med.osaka-cu.ac.jp)
        1. Department of Gastroenterology, Osaka City University, Graduate School of Medicine, Japan
          1. Tetsuya Tanigawa (ttanigawa{at}med.osaka-cu.ac.jp)
          1. Department of Gastroenterology, Osaka City University, Graduate School of Medicine, Japan
            1. Masatsugu Shiba (shiba{at}med.osaka-cu.ac.jp)
            1. Department of Gastroenterology, Osaka City University, Graduate School of Medicine, Japan
              1. Toshio Watanabe (watanabet{at}med.osaka-cu.ac.jp)
              1. Department of Gastroenterology, Osaka City University, Graduate School of Medicine, Japan
                1. Kazunari Tominaga (m1235730{at}med.osaka-cu.ac.jp)
                1. Department of Gastroenterology, Osaka City University, Graduate School of Medicine, Japan
                  1. Nobuhide Oshitani (nobu{at}med.osaka-cu.ac.jp)
                  1. Department of Gastroenterology, Osaka City University, Graduate School of Medicine, Japan
                    1. Kazuhide Higuchi (khiguchi{at}med.osaka-cu.ac.jp)
                    1. Department of Internal Medicine II, Osaka Medical College, Japan
                      1. Tetsuo Arakawa (arakawat{at}med.osaka-cu.ac.jp)
                      1. Department of Gastroenterology, Osaka City University, Graduate School of Medicine, Japan

                        Abstract

                        Background: Several studies have shown a strong association between reflux esophagitis (RE) and bronchial asthma (BA). The precise mechanisms of interaction between RE and BA are uncertain, possibly due to lack of animal models.

                        Aims: We established a novel rat model and examined pathogenic interaction of RE and BA.

                        Methods: RE and BA were induced in Brown-Norway rats by ligating the transitional region between the forestomach and the glandular portion and wrapping the duodenum near the pylorus, and by ovalbumin (OVA) sensitization and challenge with OVA aerosol. Rats were divided into four groups: control, RE, BA, and RE+BA. OVA-induced airway inflammation was assessed by number of infiltrating cells and cytokine levels in bronchoalveolar lavage fluid (BALF). Esophageal lesion index, histology, and cytokine mRNA expression as determined by real-time RT-PCR were also examined.

                        Results: Significant increases in number of cells, especially eosinophils, and IL-13 but not IFN-γ concentration in BALF were observed in the RE+BA group compared with the BA group. These enhancements of OVA-induced airway inflammation were prevented by treatment with rabeprazole. Although the esophagitis lesion index in the RE+BA group did not differ from that in the RE group, eosinophilic infiltration in the esophageal submucosa and levels of mRNA expression of cytokines such as IL-5, IL-10, IL-13, and RANTES were significantly increased.

                        Conclusion: We established a novel rat model of RE and BA, and found significant interactions of the two diseases. This model thus appears to be useful for examining the association between gastroesophageal reflux disease and bronchial asthma.

                        • GERD
                        • animal model
                        • asthma
                        • cytokine
                        • eosinophil

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