| Hypertrophic scar is a common disease in plastic surgery, which is oftenaccompanied with malformation, redness, itchiness and pain, therefore, seriously affectspatients’ physical and mental health. Until now the pathogenesis of hypertrophic scar isunclear, clinicians are eager to find a pertinent solution that can effectively prevent andtreat this disease of patients. Studies have confirmed that the immune factors played animportant role in the formation and development of scar. T lymphocytes are main immunecells in the process of scar hyperplasia. Th lymphocytes differentiate into two distinctsubsets, Th1cell and Th2cell. Both of them have a close relationship with the fibrosis ofthe scar formation. The role of Th1cells can lessen fibrosis, while Th2cells have strongeffects on promoting fibrosis. Studies have shown that the expression of a series ofchemokines in local tissue played an important role in the process of Th1, Th2cellsinfiltration. Imiquimod is clinically used as a new immune regulator for the treatment ofskin disease. Studies have shown that it can regulate Th cell expression to inhibit the action of the scar hyperplasia. This experiment from the expression of chemokinesperspective aims to study the expression changes of Th1/Th2cells related chemokines inthe process of hypertrophic scar formation and that after been applied imiquimod. Tofurther explore the pathogenesis of hypertrophic scar and possible mechanism of action ofimiquimod, the experiment is divided into two parts:The first part: Expression of Th1/Th2Cell Related Chemokines inRabbit Ear Hypertrophic Scar ModelObjective: To study the expression of Th1/Th2cells related chemokines in theprocess of rabbit ear hypertrophic scar models. Method: Sixteen New Zealand Whiterabbits were employed in this study to establish rabbit ear hypertrophic scar model andrabbit dorsal normal scar model. After fully epithelized, all the scars specimens wereharvested on the0,21st,28th,35th,42nd,49th,56th and63rd day after operation. HEstaining was performed and then measured by SEI. The expression of Th1/Th2cell relatedchemokines CXCL10,CXCL12,CCL2,CCL3,CCL4,CCL5,CCL7, CCL13,CCL14,CCL19,CCL21,CX3CL1was detected by Real-time PCR. Results: The sections of HE show themicroscopic structures of rabbit hypertrophic scar and normal scars like that of humanscares.The SEI of hypertrophic scar group showed the degree of proliferation peaked at28th day. The mRNA levels of CXCL10, CXCL12were significantly higher in theformation process of normal scar while have no expression in that of hypertrophicscar(*P<0.05). The mRNA levels of CCL2,CCL3,CCL4,CCL5,CCL7,CCL13,CX3CL1were almost none detectalbe in the formation process of normal scar while weresignificantly elevated in that of hypertrophic scar, especially the mRNA levels ofCCL2,CCL4,CCL5,CX3CL1have always maintain a high level during the scarhyperplasia period(*P<0.05). The mRNA levels of CCL14,CCL19,CCL21were almostnone detectalbe in normal scar formation and only have a low level expression only in theearly formation process of hypertrophic scar(*P<0.05). Conclusion: In the formationprocess of rabbit ear hypertrophic scar, the expression of Th1/Th2cells relatedchemokines existed difference in species, quantity and maintain time. Th1cell related chemokines CXCL10,CXCL12have low expression while Th2cell related chemokinesCCL2,CCL3,CCL4,CCL5,CCL7,CCL13,CX3CL1have significantly elevated expression,especially CCL2,CCL4,CCL5,CX3CL1maintain a high expression level. Eventually it ledto the differential ratio of Th1, Th2cells number in local tissue. Low Th1cells numberand high Th2cells quantity led to the pathological changes of the hypertrophic scar. Ourexperiment tested12kinds of chemokine expression in the process of hypertrophic scarformation by long-term and continuous detection, and sorted out the general trend of theirexpressions. Our experiment preliminary confirmed that Th1/Th2cells express imbalancein hypertrophic scar tissue, and further expounds the possible pathogenesis ofhypertrophic scar.The second part: Imiquimod Inhibit Scar hyperplasia by Regulating theExpression of Th1/Th2Cell Related Chemokines in Rabbit EarHypertrophic Scar ModelObjective: To investigate the influence on the expression of Th1/Th2cell relatedchemokines in rabbit ear hypertrophic scar by imiquimod and to discuss the inhibitoryeffect and mechanism of imiquimod on rabbit ear hypertrophic scar formation.Method:Sixteen New Zealand White rabbits were employed in this study. Rabbit ear hypertrophicscar model was established on the basis of the previous literature. All the right ear woundswere treated with5%imiquimod cream as imiquimod group and all the left ear woundswith no treated as the blank control group. The wounds were applied with cream after14thday, once a day, for a month. Both of the groups were harvested on the21st,28th,35th,42nd,49th,56th,63rd day after operation. HE and Masson staining wereperformed and then to measure SEI. The expression of Th1/Th2cell related chemokinesCXCL10,CXCL12,CCL2,CCL3,CCL4,CCL5,CCL7,CCL13,CCL14,CCL19,CCL21,CX3CL1was detected by Real-time PCR. Results: The sections of HE and Massonshowed that, compared with blank control group, the level of the collagen depositionreduced significantly in the imiquimod group. The SEI results showed imiquimod can could reduce the hyperplasia degree of hypertrophic scar(*P<0.05). The mRNA level ofTh1cell related chemokines CXCL10,CXCL12were significantly raised in imiquimodgroup than in blank control group. However the mRNA level of Th2cell relatedchemokines CCL2,CCL3,CCL4,CCL5,CCL7,CCL13,CX3CL1were significantly lower inimiquimod group than in blank control group, especially CCL2and CX3CL1have beeninhibited significantly.(*P<0.05). Conclusion: Imiquimod might inhibit rabbit earhypertrophic scar hyperplasia by regulating chemokines expression. It raised theexpression of Th1cell related chemokines and reduced the expression of Th2cell relatedchemokines to make the expression has a trend of Th1cells produced. This experimentsuggested that we could regulate the expression of Th1/Th2cells related chemokine levels,the important pathway of body’s immune system, to intervene the chemotaxis andactivation of T lymphocytes so as to achieve the effect of prevention and treatment ofhypertrophic scar, and also to provide a new train of thought for prevention and treatmentof scar. |
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