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| Author(s): |
Letícia Prado Oliveira
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia |
| Defense date: | 2017-07-10 |
| Examining board members: |
Edson Rosa Pimentel;
Aline Mara dos Santos;
Evanisi Teresa Palomari;
Glaucia Maria Tech dos Santos;
Tatiana Carla Tomiosso
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| Advisor: | Edson Rosa Pimentel |
| Abstract | |
Treatment with statins has a positive effect on the healing of injuries of many different types of tissue. In this context, the present study investigated the relative benefits of the oral administration and local application of simvastatin to the Achilles tendon following partial tenotomy. Wistar rats were treated for 7 and 21 days after partial tenotomy, and were assigned to the following groups: N (intact tendon), L7 and L21 injured tendon (no treatment); SL7 and SL21 injured tendon treated with local application of a collagen sponge soaked in simvastatin (2.2 mg/50 ?l); VL7 and VL21 injured tendon treated with local application of a collagen sponge soaked in an aqueous solution of 0.5% carboxymethylcellulose (CMC) as vehicle; SO7 and SO21 injured tendon treated by oral administration of simvastatin; VO7 and VO21 injured tendon treated by oral administration of 0.5% CMC. The interleukin 1 Beta (IL-1Beta) and transforming growth factor beta (TGF-Beta) were analysed by ELISA. Functional analyses were run in the Catwalk system. The biochemical analyses were zymography for metalloproteases 2 and 9 (MMP-2 and MMP-9), western blotting for decorin, collagen I and III, and the dosage of glycosaminoglycans (GAGs). In the morphological analyses, sections of the tendon were stained with tolouidine blue (TB), and the organization of the collagen bundles was analyzed by birefringence. For observing the ultrastructure, the tendons were analyzed by transmission electron microscopy. The group treated orally with simvastatin presented a lower concentration of IL-1Beta one day after the lesion. The SO7 group presented a significant reduction of TGF-Beta in comparison with VO7. The gait of the animals was significantly better in the SO7 and SO21 groups. All the groups analyzed at 7 and 21 days presented a significant reduction of collagen (types I and III). There was a significant increase in the active MMP-2 isoform in the L7, VL7, VO7, SO7 groups, and in the L21 and SO21 groups. In the SO7 and SO21 groups, the values recorded for both MMP-9 isoforms were similar to those of the normal group. In addition, the collagen fibrils and fibers in the SO21 group were better organized in comparison with the other injured groups after the same period of time. Our results indicate that oral treatment with simvastatin was beneficial for the recovery of the gait of the animals and the organization of the collagen fibers. Oral treatment with statins also appears to have a modulating effect on IL-1Beta, TGF-Beta and the activity of the MMPs during tendon healing. While further research is necessary, the oral administration of simvastatin appears to be a potentially useful treatment for tendon injuries (AU) | |
| FAPESP's process: | 13/04071-0 - Effect of topical and oral treatment with simvastatin in healing of partial transection of the Achilles tendon |
| Grantee: | Letícia Prado de Oliveira |
| Support Opportunities: | Scholarships in Brazil - Doctorate |