Combining use of captopril and losartan attenuates the progress of Streptococcus pneumoniae-induced tympanosclerosis through the suppression of TGF-β1 expression

• Published in: PloS one 2014-10, Vol.9 (10), p.e111620-e111620
• Main Authors: Yan, Wenqing, Li, Jianfeng, Chai, Renjie, Guo, Wentao, Xu, Lei, Han, Yuechen, Bai, Xiaohui, Wang, Haibo
• Format: Article
• Language: English
• Subjects: Albinism; Animal models; Animals; Attenuation; Blotting, Western; Brain stem; Calcification; Calcinosis - pathology; Calcium; Calcium - metabolism; Captopril; Captopril - pharmacology; Captopril - therapeutic use; Cytokines; Disease Models, Animal; Disease Progression; Drug therapy; Drug Therapy, Combination; Ear diseases; Ear, Middle - drug effects; Ear, Middle - pathology; Experiments; Gene expression; Growth factors; Guinea Pigs; Hearing - drug effects; Hospitals; Immunohistochemistry; Inoculation; Laboratories; Losartan - pharmacology; Losartan - therapeutic use; Male; Medicine and Health Sciences; Microorganisms; Middle ear; Mucosa; Mucous Membrane - drug effects; Mucous Membrane - metabolism; Mucous Membrane - pathology; Myringosclerosis - drug therapy; Myringosclerosis - microbiology; Myringosclerosis - pathology; Myringosclerosis - physiopathology; Otolaryngology; Otology; Pathogenesis; Polymerase chain reaction; Rats, Wistar; Reverse transcription; Rodents; Staining; Streptococcus infections; Streptococcus pneumoniae; Streptococcus pneumoniae - physiology; Surgery; Transforming growth factor; Transforming Growth Factor beta1 - metabolism; Transforming growth factor-b1; Transplants & implants; Wound healing
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0111620

In this study, using an Streptococcus pneumoniae-induced tympanosclerosis (TS) model, we explored the effects of captopril and losartan in the treatment of TS and the possible mechanisms. A prospective experimental animal study. We set up the TS models in both guinea pig and wistar rat by inoculation of type-3 Streptococcus pneumoniae microorganisms and then treated the animals with the combining use of captopril and losartan. Otomicroscopy was employed to observe the development of TS. Auditory brainstem response was used to test the hearing function of animals. Hematoxylin-eosin and von Kossa staining were performed to determine the morphological changes and calcium depositions. The protein expressions of transforming growth factor β1 (TGF-β1) were assessed by western blot and immunohistochemistry staining, and the mRNA level of TGF-β1 was measured by quantitative reverse transcription- polymerase chain reaction. The combining use of captopril and losartan attenuated TS responses in terms of a decrease in the TS incidence and the ABR threshold, a reduction of hyalinization and calcification in the middle ear mucosa and the thickness of the mucosa. In addition, the TGF-β1 expression was decreased at both protein and mRNA levels. Our data indicate, for the first time, that the combining use of captopril and losartan obviously attenuates TS progress through inhibiting the overexpressing of TGF-β1.