| Objective: As an immunomodulatory agent, Imiquimod is mainly used for thetreatment of genital warts. In recent years, the clinical result was satisfied fortreatment of superficial topical hemangioma, but its mechanism is not clear.There are no relevant reports in the domestic or outside literatures. The aim ofthe study was investigated to the mechanisms of treatment of imiquimod forhemangiomas by detecting tissue cytokine expression based on reliable modelof human hemangioma in nude mice in order to providing the theoretical basisfor clinical application.Method: The proliferating hemangioma tissue was obtained from the back ofright ear of5-year-old girl by surgery. The hemangioma tissue was transplantedto bilateral subcutaneous of back in30female nude mice for establishment ofthe hemangioma animal model.40days after transplantation,28successfulmodels were randomly divided into experimental group,control groups and thenatural growth group according10,9,9. Moderate amount of5%imiquimodwas evenly applied to the surface of tumor in experimental group animals bygently massage until the drug absorption every other day. Moderate amountof Vaseline was evenly applied to the surface of tumor in the control groupanimals every other day. There was no treatment for natural growth group.Every group was feeded under the same condition. Volume change andpathology specimens were measured as macro and micro data. Maximal adiameter and b diameter of every tumor are measured daily. The volume wascalculated by the formula of V=π/6×a×b2. The the volume changes in sametumor every adjacent two days were obtained by the formula of N=Vd+1-Vd.when N≤0, the tumor proliferative phase was ended. S was equal to thenumber the total group tumor in addition to the number leaving of thehyperplasia phase number. When the value of S was greater than or equal to50%in any group, five animals from every group was randomly put to death todetect the TNF-α, IL-6expression and apoptosis factor of hemangioma byimmunohistochemistry. The remaining nude mice were continue to feed assame as the original experimental method and record the experimental data.Theexperiment was terminated when all N value change stopping. The TNF-α, IL-6,apoptosis data of samples were analyzed Statistically by Software SPSS17.0. P<0.05was considered statistically significant.Results:(1) After3days of treatment, the hyperplasia phase end was appearedin the experimental group (measured N≤0). The value of S greater than or equalto50%was appeared in the experimental group after8days oftreatment. Remained nude mice continued to be feeded until the disappearanceof the last tumor volume change appeared at77days in the control group. Thevalue change of N stopped in experimental group on the60-day; Control groupwas appeared on77-day; the natural growth group was on the77-day. Compared with the other two groups, the experimental group was ahead abouttwo weeks. The Vmaxof tumor in experimental and the control group hasSignificant difference(P <0.01); The Vmaxof tumor in control group and thenatural growth has no Significant difference (P>0.05). The Vmixof tumor inexperimental and the control group has Significant difference(P<0.01); TheVmixof tumor in control group and the natural growth has no Significantdifference (P>0.05).(2). The expression of TNF and IL-6of endothelial cell ofHemangioma in the experimental group was higher than in the controlgroup(P<0.05).(3). The expression of apoptotic cells of endothelial cell ofHemangioma in the experimental group was higher than in the controlgroup(P<0.05).Conclusions:(1). The capillary hemangioma grafted in nude mice can be agood model for research on hernangioma. The growth cycle of transplantedtumor may be different according to the tissue source.(2). Imiquimod caninduce local generation of TNF-α, IL-6. The two cytokines can inhibit vascularendothelial cell growth. Therapeutic mechanism was probably be related withthe TNF-α, IL-6angiogenesis reduced and accelerated vascular endothelial cellapoptosis. |
PDF Full Text Request