Pharmacological Effects of Fasudil on Flap Survival in a Rodent Model

Ji, Encheng; Wang, Jieke; Wang, Long; Pan, Zheer; Gao, Weiyang

doi:10.1016/j.jss.2020.03.044

Cited by 3 publications

(1 citation statement)

References 45 publications

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“…Though there is already a report indicating the beneficial efficacy of Fasudil on flap survival, 19 the exact underlying mechanism remains elusive. Existent researches pointed out that in the immediate post‐elevation period, the hyperadrenergic state is thought to be a significant contributor to ischaemia 20 .…”

Section: Discussionmentioning

confidence: 99%

Dual efficacy of Fasudil at improvement of survival and reinnervation of flap through RhoA/ROCK/PI3K/Akt pathway

Wang

Fang

Chen

et al. 2022

International Wound Journal

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Fasudil is reported to be effective at protecting against ischaemic diseases, and at augmenting axon growth. In this study, we aim to evaluate its efficacy in promoting flap survival and reinnervation. Ninety‐two Institute of Cancer Research (ICR) mice were used and divided into the control, Fasudil, LY294002, Fasudil+LY294002 groups, receiving a daily intraperitoneal injection of normal saline, Fasudil (10 mg/kg), LY294002 (5 mg/kg), and Fasudil (10 mg/kg) + LY294002 (5 mg/kg), respectively. On days 0 and 5, the blood perfusion and diameter of the iliolumbar artery in the pedicle of the flaps in the four groups were evaluated using laser speckling contrast imaging (LSCI). On day 5, the flaps were photographed and the necrosis rate of the flaps was calculated using Photoshop CS6. In addition, tissues were harvested from the flaps and divided into two parts. One part underwent routine cryosection and immunofluorescent staining using the antibody against CD31 for evaluation of the microvascular density in the four groups. In the other part, the expression of RhoA, ROCK1+2, p‐CPI‐17, p‐MYPT, p‐PTEN, p‐PI3K, p‐Akt, and vascular endothelial growth factor (VEGF) within the flaps were determined using western blotting. Moreover, at days 0, 7, 15, and 30 after flap surgery, the axons within the flaps were evaluated using immunofluorescent staining with the antibody against Neurofilament‐200. It turned out that the necrosis rate was (24.4 ± 7.7)%, (5.2 ± 1.6)%, (29.8 ± 4.2)%, and (30.9 ± 7.1)%, respectively, in the control, Fasudil, LY294002, LY294002+Fasudil groups. There was a significant reduction in the necrosis rate of the flaps in the Fasudil group (P < .001). The LSCI and immunofluorescent staining demonstrated that Fasudil could significantly expand the diameter of the iliolumbar artery in the pedicle, boost the overall blood perfusion, and increase the microvascular density of the flaps in the Fasudil group (P < .05), which could all be abolished by PI3K inhibitor LY294002. On day 5, the expression of p‐CPI‐17, p‐MYPT, and p‐PTEN were downregulated, whereas pPI3K, p‐Akt, and VEGF were upregulated in the Fasudil group (P < .001). As for reinnervation, Neurofilament‐200 fluorescent staining revealed that at days 15 and 30 after flap harvest, only in the Fasudil group could new axons be observed. It can be concluded that Fasudil could simultaneously improve the survival and axon growth after flap harvest, a dual efficacy achieved by inhibition of the RhoA/ROCK pathway, which in turn activates /PI3K/AKT pathway.

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Section: Discussionmentioning

confidence: 99%

Dual efficacy of Fasudil at improvement of survival and reinnervation of flap through RhoA/ROCK/PI3K/Akt pathway

Wang

Fang

Chen

et al. 2022

International Wound Journal

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Fasudil attenuates lipopolysaccharide-induced cognitive impairment in C57BL/6 mice through anti-oxidative and anti-inflammatory effects: Possible role of aquaporin-4

Jalalkamali,

Ghahremani,

Jashn

et al. 2024

IBRO Neuroscience Reports

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Protective Effect of Fasudil on Testicular Ischemia-Reperfusion Injury in Rats

Kaya,

Kapisiz,

Eryilmaz

et al. 2024

DDDT

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Background Ischemia-reperfusion (I/R) injury to the testis can lead to organ damage, infertility, and subfertility. The goal of this study was to investigate the effects of fasudil on this devastating condition. Methods Thirty male Long-Evans rats were divided into five groups: a control group (no torsion), rats administered fasudil (30 mg/kg, no torsion), rats subject to ischemia with no treatment (I) (I/R injury), injured rats that received treatment 1 (T1) (I/R with 30 mg/kg fasudil before detorsion), and injured rats that received treatment 2 (T2) (I/R with 30 mg/kg fasudil after detorsion). Serum levels of TNF-ɑ and IL-6, along with tissue levels of glutathione (GSH), malondialdehyde (MDA), caspase-3, and Johnsen Tubular Biopsy Score (JTBS), were measured. Results Group I exhibited significantly higher levels of MDA and caspase-3 than all other groups except T2 (p ˂ 0.05). Although the difference was not statistically significant, Group T2 exhibited lower MDA and caspase-3 levels than Group I (p ˃ 0.05). Additionally, Group I displayed significantly higher TNF-ɑ and IL-6 levels, and lower GSH and JTBS values, than the other groups (p ˂ 0.05). Conclusion Our findings indicate that fasudil protects the testis from I/R injury, particularly when administered early.

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Pharmacological Effects of Fasudil on Flap Survival in a Rodent Model

Cited by 3 publications

References 45 publications

Dual efficacy of Fasudil at improvement of survival and reinnervation of flap through RhoA/ROCK/PI3K/Akt pathway

Dual efficacy of Fasudil at improvement of survival and reinnervation of flap through RhoA/ROCK/PI3K/Akt pathway

Fasudil attenuates lipopolysaccharide-induced cognitive impairment in C57BL/6 mice through anti-oxidative and anti-inflammatory effects: Possible role of aquaporin-4

Protective Effect of Fasudil on Testicular Ischemia-Reperfusion Injury in Rats

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