title: Combining use of captopril and losartan attenuates the progress of Streptococcus pneumoniae-induced tympanosclerosis through the suppression of TGF-β1 expression.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  A prospective experimental animal study.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, P.R. China; Shandong Institute of Otolaryngology, Jinan, P.R. China.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, P.R. China; Shandong Institute of Otolaryngology, Jinan, P.R. China; Shandong Provincial Key Laboratory of Otology, Jinan, P.R. China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing, P.R. China.
authors.forename: Renjie
authors.initials: R
authors.lastname: Chai
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, P.R. China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, P.R. China.
authors.forename: Yuechen
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, P.R. China; Shandong Institute of Otolaryngology, Jinan, P.R. China; Shandong Provincial Key Laboratory of Otology, Jinan, P.R. China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, P.R. China; Shandong Institute of Otolaryngology, Jinan, P.R. China; Shandong Provincial Key Laboratory of Otology, Jinan, P.R. China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002114:Calcinosis / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002216:Captopril / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D018450:Disease Progression; D004359:Drug Therapy, Combination; D004432:Ear, Middle / Q000187:drug effects / Q000473:pathology; D006168:Guinea Pigs; D006309:Hearing / Q000187:drug effects; D007150:Immunohistochemistry; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D063371:Myringosclerosis / Q000188:drug therapy* / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology; D017208:Rats, Wistar; D013296:Streptococcus pneumoniae / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D053773:Transforming Growth Factor beta1; D002216:Captopril; D019808:Losartan; D002118:Calcium