The Inhibitory Effect Of Different Routes Of Tranexamic Acid To Treat NB-UVB-induced Guinea Pigs Pigmentation Model

Objective: Since 1979,for the first time,Japanese scholars discovered and reported that oral Tranexamic Acid(TA)have a therapeutic effect on melasma,domestic and foreign scholars conducted a number of studies for the treatment of TA on melasma and has made outstanding contribution for slinical treatment of melasma.But there has been few reported about differences in the curative effect of different routes of administration of TA in treatment of melasma and other pigmentation disorders.In this study,we through putting brown Guinea pigs to expose to narrow band ultraviolet B(NB-UVB)to induce skin pigmentation as animal models.By different routes of administration of TA to treat guinea pigs skin pigmentation,finding the influence of the number of melanocyte,synthetic of melanin granules and positive expression of HMB45.Explore the the best routes of administration of TA to treat pigmentation disorders,provide a theoretical basis for the clinical treatment of pigmentation disorders.Methods:1 The induction of the pigmentation animal model:30 healthy guinea pigs(ordinary grade),female,1~2months old,weighing 260g~376g,319 g average,yellowish-brown part skin unhairing and accept the NB-UVB irradiation.Adjust the focus before irradiation,so that the two red lights coincide,the dose was 900 mJ/cm2,once a week[1],a total of 3 times,total dose 2700 mJ/cm2.2 Grouping and Processing:After the model success,the 30 guinea pigs were randomly divided into four groups,including control group six animals and each treatment group eight animals.Control group: no treatment.Group A:TA intravenous drip treatment,1 times/week.Group B:TA intradermal injection treatment,1time/day.Group C: oral TA treatment tablets,2times/day.Each route of administration a course of 30 days.3 Evaluation:(1)Before the NB-UVB irradiation,before treatment,after treatment 2,4,6 weeks.Take picture for each guinea pig and assess the change of pigmentation of its modeling area.(2)Guinea pig of each group draw materials at the same observation point above-mentioned.So we can exclude the interference of time factor to the experiment.Respectively use melanocyte dyeing method(Imokawa method)[2],melanin particles dyeing method(Masson-Fontana method)[3] and immunohistochemical staining(monoclonal antibody of melanocyte HMB45)[4],observe epidermal hyperpigmentation,epidermis melanocyte number,change of melanin granules expression and HMB45 positive expression.4 Analysis of results: Use IBM SPSS 21.0 statistical software for statistical description and factorial design analysis of variance of each indicator.Results: 1 Successfully prepared pigmentation animal model after NB-UVB irradiation to the brown skin of guinea pig.There were no obvious edema,blisters and desquamation on guinea pigs’ modeling skin after exposed to NB-UVB irradiation.After 4~6 days,mild erythema and uneven pigmentation spots were found,then compared with normal skin gradually deepen and more uniform;2 Change of the pigmentation score,the number of MC,the synthesis of melanin granules as well as HMB45 positive expression:(1)After the observation,modeling region skin of each group have varying degrees pigmentation reduce.Wherein guinea pig’s skin colorin intravenous drip group and intradermal injection group returned to the level of before irradiation.Oral group guinea pig’s skin was still mild pigmentation than before irradiation.The control group decreased less and pigmentation had no significant improvement.Each group pigmentation scores were: Control group: 1.83±0.40,intravenous drip group: 0.37±0.51,intradermal injection group: 0.50±0.53,oral group:0.62±0.76;(2)Change of the number of MC,the synthesis of melanin granules as well as HMB45 positive expression: The control group were: 427.50±2.25,0.89±.086,0.87±0.10.The treatment group modeling skin’s epidermal hyperpigmentation score,number of MC,percentage change of melanin granules in epidermal,percentage change of positive expression of HMB45 in epidermal were significantly lower than control group.Among them,pigmentation score and number of MC in intravenous and intradermal injection group were close to the level of irradiation before.Respectively: 391.75 ± 10.87,392.87 ±8.95,oral group: 413.75±9.80.Epidermal melanin granules area as a percentage of the epidermis skin area accounted: intravenous drip group: 0.62±0.06,intradermal injection group: 0.70±0.05,oral group:0.77±0.09.Positive expression of HMB45 as a percentage of the epidermis skin area accounted: intravenous drip group: 0.42±0.22,intradermal injection group: 0.54±0.18,oral group:0.72±0.26.Experimental and statistical results showed that: TA intravenous drip treatment and intradermal injection treatment had a faster and more obvious effect in the treatment of pigmentation than control group,it means there were statistics difference(P<0.05).And intravenous drip and intradermal injection of TA were more effective than oral routs(P<0.05).However,there were no statistics difference in pigmentation rating between TA intravenous drip treatment and intradermal injection treatment(P>0.05).We can believe that the inhibition of pigmentation between those two routs had no diffrence.Oral TA and control group had no significant difference on evaluation of pigmentation(P>0.05),we believe oral TA in this experiment had no significant inhibitory effect on pigmentation.Conclusions: Different routes of TA to treat NB-UVB-induced guinea pigs pigmentation had varying degrees inhibition effective.Analysis the indicators of change of the pigmentation score,the number of MC,the synthesis of melanin granules as well as HMB45 positive expression.TA intravenous drip treatment and intradermal injection treatment had a strong inhibition of pigmentation.Oral TA had no significant inhibition of pigmentation.