Abstract:

Objective To study the possible mechanisms of influence of different doses of UVA1 on the development of hypertrophic scar in rabbit ears induced by excision of full-thickness skin. Methods A hypertrophic scar model was established by excision of full-thickness skin on the ventral surface of rabbit ears. A total of 24 New Zealand white rabbits were randomly and equally divided into 4 groups to receive UVA1 radiation on the left ear immediately （U0 group）, 1 month （U1 group）, 2 months （U2 group） and 3 months （U3 group） after the excision, respectively, and each group were classified into two subgroups to be irradiated with UVA1 of 60 （middle） and 110 （high） J/cm2, respectively, for 30 sessions. The right ears served as the control without irradiation. Skin samples were obtained from the ears of rabbits before the first and after the last irradiation, transmission electron microscopy （TEM） was used to observe the ultra-structure and morphology of collagen fiber and fibroblasts, and immunohistochemical staining was performed to measure the expressions of matrix metalloproteinases （MMP）-1, tissue inhibitor of metalloproteinase （TIMP）-1, transforming growth factor （TGF）-β1, proliferating cell nuclear antigen （PCNA） and α-smooth muscle actin （α-SMA） in skin samples. Results Compared with the unirradiated skin, irradiated skin showed higher expression levels of MMP-1 （P < 0.05）, which were 10.43 ± 1.61 and 11.16 ± 1.57 in middle- and high-U1 group, 8.63 ± 2.61 and 7.33 ± 1.58 in middle- and high-U2 gorup, 5.74 ± 1.43 and 3.11 ± 0.27 in middle- and high-U3 group respectively. The expression level of TGF-β1 in irradiated skin was 12.51 ± 4.13 and 12.02 ± 5.02 in middle- and high-U1 group, respectively, 18.74 ± 6.42 and 19.69 ± 4.52 in middle- and high-U2 group, respectively, 20.51 ± 1.78 and 29.45 ± 6.55 in middle- and high-U3 group, respectively. A significant decrease was observed in the expression of PCNA in irradiated skin in middle- and high-U1 group （2.67 ± 0.44 and 2.04 ± 0.65）, middle- and high-U2 group （4.50 ± 0.97 and 5.82 ± 0.68）, middle- and high-U3 group （7.45 ± 1.47 and 8.16 ± 1.07） in comparison with unirradiated skin （all P < 0.05）. There was a lower expression of TIMP-1 in irradiated skin of high-U1, -U2, and -U3 group （12.74 ± 4.58, 15.17 ± 3.26, 20.72 ± 3.31, all P < 0.05） as well as α-SMA in that of high-U1, middle-U1 and high-U2 group （1.33 ± 0.34, 2.04 ± 0.20, 3.60 ± 1.75, all P < 0.05） compared with the unirradiated skin. Further more, a significant increment was observed in the expressions of TGF-β1 （23.90 ± 2.92, P < 0.05） in irradiated skin of high-U0 group, PCNA（7.42 ± 0.65 and 7.59 ± 0.31）, TIMP-1 （29.82 ± 1.94 and 33.51 ± 1.19） and α-SMA （6.31 ± 0.61 and 2.97 ± 0.56） in irradiated skin of middle- and high-U0 group, but a decline in the expression of MMP-1 （2.25 ± 0.38, P < 0.05） in irradiated skin of high-U0 group in comparison with the unirradiated skin. TEM showed that the collagen fiber diameter turned small, and fibroblasts, most of which were quiescent, showed a reduction in cytoplasm volume with the presence of immature organelles, after high-dose UVA1 irradiation. Conclusions The therapeutical effect of UVA1 on scar may be realized by accelerating the degradation of matrix proteins and decelerating the proliferation of fibroblasts and myofibroblasts via downregulating the expressions of TGF-β1, TIMP-1 and α-SMA and upregulating the expression of MMP-1. However, the results would be opposite if the interference with UVA1 irradiation is given at the early stage of wound healing.

Key words: Animal