Pharmacological Effects of Fasudil on Flap Survival in a Rodent Model

• Published in: The Journal of surgical research 2020-11, Vol.255, p.575-582
• Main Authors: Ji, Encheng, Wang, Jieke, Wang, Long, Pan, Zheer, Gao, Weiyang
• Format: Article
• Language: English
• Subjects: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - administration & dosage; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives; Akt signaling pathway; Animals; Apoptosis; Apoptosis - drug effects; Autophagy; Autophagy - drug effects; Disease Models, Animal; Graft Survival - drug effects; Humans; Injections, Intraperitoneal; Male; Necrosis - drug therapy; Necrosis - etiology; Neovascularization, Physiologic - drug effects; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase Type III - metabolism; Oxidative Stress - drug effects; Perforator Flap - adverse effects; Perforator Flap - transplantation; Protein Kinase Inhibitors - administration & dosage; Proto-Oncogene Proteins c-akt - metabolism; Rats; ROCK; Signal Transduction - drug effects
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2020.03.044

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. 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. 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. In conclusion, fasudil treatment decreased necrosis of perforator flaps possibly by affecting the Akt/eNOS/NO pathway, attenuating apoptosis and activating autophagy.