The Study Of Dynamic Expression Of TNF-α And TNF-α R₁ Genes In Hypertrophic Scars And Its Significance

【Objective】 To study the distribution and expression of Tumor necrosis factor alpha(TNF-α) and its receptor TNF-αR₁ in the different period of hypertrophic scars; To understand the role of Tumor necrosis factor alpha(TNF-α) and its receptor TNF-αR₁ when the hypertrophic scar came into being and proceeded ; To further find out the mechanism of action of TNF-αand TNF-αR₁ and then a valid way of gene therapy could be discoverded in order to cure the hypertrophic scar .【Method】The levels of protein of TNF-αin hypertrophic scar and normal scar samples were investigated by utilizing molecular biological , immuno-histochemical and pathological techniques : (1) The percentage of TNF-αcells was analyzed in hypertrophic scar (N=33) and normal scar (N=5) biopsies Using monoclonal antibodies and immunoperoxidase staining of paraffin tissue sections ; (2) TNF-αmRNA expression in the different period of hypertrophic scars (N=33) ,normal scar (N=5)biopsies were tested by a semiquantitative reverse polymerase chain reaction (RT-PCR)method ; (3) TNF-αR1 mRNA expression in the hypertrophic scars over one year were tested by a semiquantitative reverse polymerase chain reaction (RT-PCR)method .【Result】 (1) As the hypertrophic scars getting mature ,there was a significant increase in activated infiltrating cells capable of producing TNF-α(P<0.01) . In contrast , The percentage of TNF-α-positive cells was significantly lower than that detected in normal scars . In fact , compared to29.84% of the TNF-α-positive cells in normal scars , the positive staining with anti-TNF-αmAb were restricted to 4.93% , 7.57% , 10.96% and 13.24% of tissue -infiltrating cells respectively in hypertrophic samples of less than 3 months , 3～6 months , 7～12 months and more than 12 months ; (2) In different period of hypertrophic scars , the expression of TNF-αmRNA was the same as that of TNF-αprotein ; (3) Compared with normal scars , TNF-αR₁ mRNA expression in the hypertrophic scars over one year was the same(P>0.05) .【Conclusion】These results suggest that TNF-αmay play an important role in normal wound healing and that the formation of hypertrophic scar could rather be due to the lack of TNF-α than be the down-regulating of the number of TNF-αreceptor 1; The maturation of hypertrophic scar might be partially a consequence of a relatively high amount of TNF-α; It was a vilid way to cure the hypertrophic scars that improving the the production of TNF-αthrough gene therapy in earlier state of hyphertrophic scar .