ABSTRACT
BACKGROUND: Nowadays, it is thought that transforming growth factorβ (TGFβ) is closely related with cicatrization. TGFβ that is a key active molecule can affect each phase of cicatrization. Theoretically, to inhibit the biological effect of TGF β can reduce cicatrization.OBJECTIVE: To explore the inhibitive effect of antisense TGF β1 deoxy-oligonucleotide on generation of cicatricle in intention of animal models with hyperplastic scars and observe the effective route of administration of using antisense TGF β1.DESIGN: Own control and animal study.SETTING: Department of Plastic Surgery, Anning Hospital of General Hospital, Lanzhou Military Area Command of Chinese PLAMATERIALS: The experiment was performed at the laboratory of anatomy,Lanzhou Medical College from September 2002 to July 2003. Totally 20flap-eared Japanese rabbits were selected.METHODS: Blood vessels could be seen in ventral surface of each rabbits' ear getting out of the way along long axis to establish two 1.0 cm×2.5 cm oblong full-thickness cutaneous deficiency raw surfaces that interval for 1.5 cm, to the surface of cartilage, totally 80, so asto establish ventral surface of rabbits' ear models with hyperplastic scars. After epithelizatio of raw surfaces of rabbits' ear (20 days, averagely), 5μL(1 g/L) antisense TGF β1 deoxy-oligonucleotide was closely injected into local endepidermis of each raw surface of left ear of each rabbit with microinjector, which was regarded as TGF β1 group. 5 μL saline was injected into each raw surface of right ears, which was regarded as saline control group. After injection for3, 7, 11, 20, 30 days, cicatricial tissues were cut, 4 rabbits in each time phase. Hematoxylin-esoin (HE) staining, Masson staining and TGFβ1 mRNA, type Ⅰ and Ⅲ collagen mRNA in situ hybridization histochemistry staining were applied.MAIN OUTCOME MEASURES: Results of HE staining, Masson staining and in situ hybridization histochemistry staining.RESUTLS: A total of 20 animals were included in the result analysis. ①HE staining showed that inflammatory cell infiltration and significant infiltrative zone of leukocytes occurred in hyperplastic scars of right ears in each group. There was inflammatory cell infiltration, but no infiltrative zone of leukocytes in hyperplastic scars of left ears after intervention with antisense TGF β1. ②Masson staining suggested that collagen fibers with deep blue-stain occurred in hyperplastic scars of right ears from the 3rd week after injury, till the 7th week there still was blue-stain collagen fibers,which was bulky (width of about 8-10 μm) and arranged in a great mess.The blue-stain collagenous fibers also appeared in hyperplastic scars of left ears at the 3rd week after injury by the intervention of antisense TGF β1,but till the 6th and 7th weeks the blue-stain became light and thin (width of about 3-5 μm), arranged in order. ③In situ hybridization revealed that expressive rates of TGF β1 mRNA, type Ⅰ collagen mRNA, type Ⅲ collagen mRNA positive cells decreased obviously.CONCLUSION: Antisense TGF β1 can inhibit the proliferation of hyperplastic scars of rabbits' ears and lighten markedly the fibrosis of cicatricial tissue. The local injection with naked DNA is feasible in the treatment of cicatricle.