Doxycycline Attenuates Isoproterenol-Induced Myocardial Fibrosis and Matrix Metalloproteinase Activity in Rats
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概要
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Our objective was to investigate the effects of doxycycline, a matrix metalloproteinase (MMP) inhibitor (MMPi) on β-agonist-induced myocardial fibrosis and MMP expression. Twenly-four Wistar-Kyoto rats were divided into 3 groups: control (CTL; n=8), isoproterenol (ISO; n=8), and isoproterenol with doxycycline (ISO+DOX; n=8). ISO and ISO+DOX rats received L-isoproterenol (2.0 mg/kg/d) for 14 d, whereas the CTL group received vehicle. In addition, ISO+DOX rats received a subcutaneous injection of doxycycline (25 mg/kg/d) for 14 d, whereas CTL and ISO rats were injected with saline. Cardiac fibrosis was evaluated via histopathological analysis. MMP-2 and -9 were analyzed by Western blotting and zymography. Compared to the control, the myocardial cross-sectional area and areas of fibrosis were increased significantly in the ISO group, but were attenuated in the ISO+DOX group. MMP-2 activity also increased significantly in the ISO group, but decreased in the ISO+DOX group. Similarly, immunoblotting showed significant increase in MMP-2 and -9 levels in the ISO group, and decreased levels in the ISO+DOX group. Our results suggest that the enhanced expression of MMPs plays a prominent role in promoting myocardial fibrosis in β-agonist signaling pathway, and that MMP-inhibiting compounds may attenuate myocardial fibrosis.
- 公益社団法人 日本薬学会の論文
著者
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Hara Yukio
Department Of Veterinary Pharmacology School Of Veterinary Medicine And Animal Sciences Kitasato Uni
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Yoshioka Kazuki
Laboratory of Veterinary Anatomy, School of Veterinary Medicine, Kitasato University
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Kanai Kazutaka
Laboratory of Small Animal Internal Medicine, School of Veterinary Medicine, Kitasato University
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Hoshi Fumio
Laboratory of Small Animal Internal Medicine, School of Veterinary Medicine, Kitasato University
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Itoh Naoyuki
Laboratory of Small Animal Internal Medicine, School of Veterinary Medicine, Kitasato University
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Hori Yasutomo
Laboratory Of Small Animal Internal Medicine School Of Veterinary Medicine Kitasato University
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Kunihiro Shoh-ichi
Laboratory of Small Animal Internal Medicine, School of Veterinary Medicine, Kitasato University
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Sato Shingo
Laboratory of Small Animal Internal Medicine, School of Veterinary Medicine, Kitasato University
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Higuchi Seiichi
Laboratory of Small Animal Internal Medicine, School of Veterinary Medicine, Kitasato University
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Hara Yukio
Department of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University
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