Objective o explore the efficacy of the strong ROCK inhibitor GSK429286A in promoting the survival and sensory recovery of extended flaps in rats. Methods 32 male SD rats were adopted and extended flaps measuring 10 cm×3 cm based on the iliolumbar perforator were harvested. The rats were then equally divided into a control group and a GSK429286A group (administered intraperitoneally at a dose of 10 mg/kg), and into 7 and 30 days after surgery. At day 7, the flaps were photographed for calculation of necrosis rates. Subsequently, laser Doppler contrast imaging was used to assess blood perfusion in the second choke zone. At day 30, the sensory recovery of the flaps in both groups was evaluated using the cutaneous trunci muscle reflex (CTMR). Tissue samples from the second choke zone were collected at day 7 and 30, and immunohistochemical staining with α-SMA and NF-200 antibodies was performed to visualize the vessels and nerves. For in vitro study, dorsal root ganglia (DRG) were obtained from 15-day pregnant rats and divided into the control and GSK429286A groups. After treatment with GSK429286A (10 mmol/L) for 3 days, Tuj1 antibody was used to stain the DRG axons, and the length of DRG axons was measured. The Independent sample t-test was used to compare the data between the two groups. Results The necrosis rates in the control and GSK429286A groups were (19±7) % and (11±5) %, respectively, showing a significant difference (P=0.032). The vascular diameter in the second choke zone of the control and GSK429286A groups were 81±8 um and 106±7 um, respectively, also demonstrating a significant difference (P<0.001). In accordance, blood perfusion in the second choke zone was (67±5) PU in the GSK429286A group, significantly higher than 45±11 PU in the control group (P=0.002). At day 30, abundant NF-200-positive nerve fibers could be observed within the flaps of the GSK429286A group, resulting in positive CTMR. In contrast, no NF-200-positive nerve fibers could be observed in the control group, resulting in negative CTMR. Conclusions The strong ROCK inhibitor GSK429286A can simultaneously promote the survival and sensory recovery of flaps in rats.
Key words
GSK429286A /
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ROCK inhibitor /
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Flap necrosis /
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Nerve regeneration
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