Treatment Evaluation with a serinoprotease inhibitor in a smoke-induced emphysema model

• Grant number: 13/04488-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2013
• End date: August 31, 2015
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Fernanda Degobbi Tenorio Quirino dos Santos Lopes
• Grantee: Juliana Dias Lourenço
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Previous study in our laboratory showed that the treatment with BmTIA, a serinoprotease inhibitor, attenuated the alveolar destruction in mice submitted to a protocol of emphysema by porcine pancreatic elastase (PPE) instillation. Considering that the tabagism is the main factor for the DPOC development and that the cigarette smoke exposition is considered the best experimental model to mimetize the human emphysema disease, we will verify the effects of BmTIA inhibitor in a smoke-induced model. For that, mice C57BL/6 will be exposed to cigarette smoke (two times / day/ 30 minutes/ 5 days per week/during 12 weeks) (Smoke Group). Animals will receive two doses of BmTIA inhibitor. We will give the first dose 24h after the last exposition to cigarette smoke and the second dose at the 7th day after the first treatment instillation (Smoke-BMTIA Group). The Control Group will receive treatment with Saline Solution, the BmTIA vehicle (Smoke-VE Group). Two animal groups will be remained exposed to ambient air, and one of these will receive treatment with BmTIA (Control Group, Control-BMTIA). Respiratory Mechanics assessment and the analysis of the inflammatory profile in BAL will be performed in anesthetized animals. We will evaluate by lung morphological analysis: Lm, the volume proportion of elastic and collagen fibers in parenchyma and by immunohistochemistry: positive cells for MAC-2, MMP-12, MMP-9 and neutrophils. We will also evaluate the gene expression of MMP-12 and 9 by PCR.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

LOURENCO, JULIANA D.; ITO, JULIANA T.; CERVILHA, DANIELA A. B.; SALES, DAVI S.; RIANI, ALYNE; SUEHIRO, CAMILA L.; GENARO, ISABELLA S.; DURAN, ADRIANA; PUZER, LUCIANO; MARTINS, MILTON A.; et al. The tick-derived rBmTI-A protease inhibitor attenuates the histological and functional changes induced by cigarette smoke exposure. HISTOLOGY AND HISTOPATHOLOGY, v. 33, n. 3, p. 289-298, MAR 2018. (13/04488-8)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

LOURENÇO, Juliana Dias. Evaluation of a serine protease inhibitor treatment in an experimental model of cigarette smoke-induced emphysema. 2016. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.