YUAN Jishan 1 , LI Tianzeng 2 , QI Shaohai 2
  • 1Department of Orthopedics, the Affiliated People’s Hospital of Jiangsu University, Zhenjiang Jiangsu, 212002, P.R.China;;
  • 2Department of Burns, the First Affiliated Hospital, Sun Yat-sen University.;
Col I A1; Antisense oligodeoxyneucleotide; Hypertrophic scar; Collagen; Nude mouse
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Objective Col I A1 antisense oligodeoxyneucleotide (ASODN) has inhibitory effect on collagen synthesis in cultured human hypertrophic scar fibroblasts. To investigate the effects of intralesional injection of Col I A1 ASODN on collagen synthesis in human hypertrophic scar transplanted nude mouse model. Methods The animal model of human
hypertrophic scar transplantation was established in the 60 BALB/c-nunu nude mice (specific pathogen free grade, weighing about 20 g, and aged 6-8 weeks) by transplanting hypertrophic scar without epidermis donated by the patients into the interscapular subcutaneous region on the back, with 1 piece each mouse. Fifty-eight succeed models mice were randomly divided into 3 groups in accordance with the contents of injection. In group A (n=20): 5 μL Col I A1 ASODN (3 mmol/L), 3 μL l iposome, and 92 μL Opti-MEM I; in group B (n=20): 3 μL l iposome and 97 μL Opti-MEM I; in group C (n=18): only 100 μL Opti-MEM I. The injection was every day in the first 2 weeks and once every other day thereafter. The scar specimens were harvested at 2, 4, and 6 weeks after injection, respectively and the hardness of the scar tissue was measured. The collagens type I and III in the scar were observed under polarized l ight microscope after sirius red staining. The ultrastructures of the scar tissues were also observed under transmission electronic microscope (TEM). Additionally, the Col I A1 mRNAs expression was determined by RT-PCR and the concentrations of Col I A1 protein were measured with ELISA method. Results Seventeen mice died after intralesional injection. Totally 40 specimens out of 41 mice were suitable for nucleic acid and protein study, including 14 in group A, 13 in group B, and 14 in group C. The hardness of scars showed no significant difference (P  gt; 0.05) among 3 groups at 2 weeks after injection, whereas the hardness of scars in group A was significantly lower than those in groups B and C at 4 and 6 weeks (P  lt; 0.05), and there was no significant difference between groups B and C (P  gt; 0.05). The collagen staining showed the increase of collagen
type III in all groups, especially in group A with a regular arrangement of collagen type I fibers. TEM observation indicated that there was degeneration of fibroblasts and better organization of collagen fibers in group A, and the structures of collagen fibers in all groups became orderly with time. The relative expressions of Col I A1 mRNA and the concentrations of Col I A1 protein at 2 and 4 weeks after injection were significant difference among 3 groups (P  lt; 0.05), and they were significantly lower in group A than in groups B and C (P  lt; 0.05) at 6 weeks after injection, but no significant difference was found between groups B and C (P  gt; 0.05). Conclusion Intralesional injection of Col I A1 ASODN in the nude mice model with human hypertrophic scars can inhibit the expression of Col I A1 mRNA and collagen type I, which enhances the mature and softening of the scar tissue. In this process, l iposome shows some assistant effect.

Citation： YUAN Jishan,LI Tianzeng,QI Shaohai. EFFECT OF Col I A1 ANTISENSE OLIGODEOXYNEUCLEOTIDE ON COLLAGEN SYNTHESIS IN HUMAN HYPERTROPHIC SCAR TRANSPLANTED NUDE MOUSE MODEL. Chinese Journal of Reparative and Reconstructive Surgery, 2011, 25(6): 718-723. doi: Copy