Pharmacological Effects of Fasudil on Flap Survival in a Rodent Model
| Autor: | Zheer Pan, Jieke Wang, Encheng Ji, Long Wang, Weiyang Gao |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
Necrosis Nitric Oxide Synthase Type III Neovascularization Physiologic Apoptosis Pharmacology Nitric Oxide Nitric oxide 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Enos 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine Autophagy medicine Animals Humans Protein Kinase Inhibitors Protein kinase B biology business.industry Akt/PKB signaling pathway Graft Survival Fasudil Malondialdehyde biology.organism_classification Rats Vascular endothelial growth factor Disease Models Animal Oxidative Stress chemistry 030220 oncology & carcinogenesis 030211 gastroenterology & hepatology Surgery medicine.symptom business Perforator Flap Proto-Oncogene Proteins c-akt Injections Intraperitoneal Signal Transduction |
| Zdroj: | Journal of Surgical Research. 255:575-582 |
| ISSN: | 0022-4804 |
| DOI: | 10.1016/j.jss.2020.03.044 |
| Popis: | Background Necrosis of the perforator flap is a critical problem. Fasudil, an inhibitor of Rho-associated coiled-coil containing kinase, has antiapoptosis activity and attenuates oxidative stress in many diseases. We characterized the effects of fasudil through intraperitoneal injection on perforator flap survival and identified its possible mechanism. Methods and materials Rats were divided into a control group (without surgery), a flap group (only surgery), and a fasudil group (surgery plus fasudil). Perforator flaps were made on the backs of the rats. The expression of vascular endothelial growth factor, the protein kinase B (PKB/Akt), endothelial nitric oxide synthase, Bax, Bcl-2, Beclin-1, P62, and LC3 II/LC3 I was determined by Western blot at day 3 after surgery. Nitric oxide (NO) components, superoxide dismutase, and malondialdehyde were also measured at day 3. The survival rate and laser Doppler perfusion imaging were performed at day 7 after surgery. Result The group with fasudil treatment exhibited the higher survival rates and angiogenesis levels. Fasudil also induced the activation of Akt/eNOS/NO pathway detected by the Western blot and NO expression kit. Furthermore, Western blot results showed fasudil-attenuated apoptosis through a raised Bcl-2/Bax rate and enhanced autophagy levels through raised beclin-1, decreased p62, and the elevated rate of LC3 II/LC3 I. Finally, fasudil increased superoxide dismutase and decreased malondialdehyde. Conclusions In conclusion, fasudil treatment decreased necrosis of perforator flaps possibly by affecting the Akt/eNOS/NO pathway, attenuating apoptosis and activating autophagy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect