Objective To compare effects of two commonly used Rho kinase inhibitors, Fasudil and Y27632, on promoting cutaneous nerve regeneration. Methods Firstly, 15 Sprague Dawley rats were used to establish a clamp-induced injury model on the saphenous nerve. They were then divided into the control, Fasudil and Y27632 groups, and intraperitoneal given DMSO, Fasudil （40 mg/kg） or Y27632 （40 mg/kg）, respectively, once a day for 7 days after surgery. Then, the regenerated axons within the saphenous nerve were evaluated. Secondly, perforator flaps were harvested on the back of 15 ICR mice, which were equally divided into the above-mentioned three groups with drugs administered accordingly. 30 days later, axons within the flaps were quantitatively analyzed. Finally, the rat embryonic dorsal root ganglias （DRG） were collected and cultured in PDMS molds to establish an in vitro axotomy model, which were then divided into the above-mentioned three groups and treated accordingly. The length of regenerated DRG axons was measured after 3 days. One-way analysis of variance was used to process the data. Results One week after saphenous nerve injury, the density of new axons in the control, Fasudil and Y27632 groups was （43.2±6.5）%, （55.8±5.2）% and （68.0±2.3） %, respectively. The axon density of the Y27632 group was significantly higher than those of the other 2 groups （P<0.01）. One month after flap surgery, the nerve density of the distal cross-section of the flap in the control, Fasudil and Y27632 was （1.1±1.1）‰, （2.8±0.5）‰ and （6.0±0.9）‰, respectively. The nerve density of the flap in the Y27632 group was significantly higher than the other 2 groups （P<0.001）. 3 days after DRG axotomy, the expression of SPRR1a, ATF3, c-JUN, GAP43, RhoA and ROCK2 significantly increased. The length of the regenerated axons and the area of growth cones of DRG in the control, Fasudil and Y27632 groups were （1916±132） μm and （40±7） μm2, （2302±134） μm and （55±7） μm2, and （2662±112） μm and （79±5） μm2, respectively. The length of the regenerated axons and the area of growth cones of DRG in the Y27632 group were significantly larger than that of the other 2 groups （P<0.05）. Conclusions Y27632 is more capable than Fasudil to promote DRG growth cone expansion and repair after cutaneous nerve injury, and is very suitable for promoting sensory recovery after skin flap surgery.
Key words
Flap; /
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Nerve regeneration; /
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RhoA/ROCK; /
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Fasudil; /
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Y27632
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