复方大黄制剂对家兔足肢长春瑞滨外渗皮肤毒性反应防治作用观察

Preventive and therapeutic effects of compound rhubarb preparation on vinorelbine extravasation-induced skin toxicity of rabbit foot limbs

目的：观察复方大黄制剂对长春瑞滨外渗引起的家兔足肢皮肤毒性反应的防治作用及用药安全性。方法中国兔32只。取25只随机分为A组7只、B组7只、C组7只、D组4只。将家兔左前肢脱毛备皮，取备皮后中央区，A、B、C组制作长春瑞滨外渗皮肤毒性反应模型，D组皮下注射生理盐水。 A组同时给予复方大黄制剂热敷、外涂；B组同时予盐酸利多卡因＋地塞米松＋生理盐水做环形皮下局部注射。建模1周后处死动物，取建模区皮肤及皮下组织进行大体及病理观察。取家兔7只，每只均设完整皮肤给药区、破损皮肤给药区和完整皮肤对照区、破损皮肤对照区，给药区涂抹复方大黄酊，对照区涂以纯净水。分别于1、12、24、48、72 h后观察皮肤刺激反应情况。结果造模后7 d，A组发生Ⅰ°皮肤毒性反应4只、Ⅱ°3只；B组Ⅰ°5只、Ⅱ°2只；C组Ⅱ°2只、Ⅲ°4只、Ⅳ°1只；D组Ⅰ°4只。 A、B组与C组皮肤毒性反应程度相比，P均＜0．01。 A、B组较C组皮下组织病理改变明显好转，与D组差异不大。家兔破损皮肤给药后1 h内皮肤刺激反应积分平均为1．5分，属于轻度刺激反应，之后为0．0～0．4分，属于无皮肤刺激反应。结论复方大黄制剂可减轻长春瑞滨外渗所致的皮肤毒性反应，对皮肤刺激性小。

Objective To observe the preventive and therapeutic effects of compound rhubarb preparation on skin toxic-ity of rabbit foot limbs caused by vinorelbine extravasation as well as the drug safety.Methods There were 32 Chinese rab-bits.Twenty-five rabbits were selected and randomly divided into group A with 7 rabbits, group B with 7 rabbits, group C with 7 rabbits and group D with 4 rabbits.Rabbits＇left forelimb were shed and made skin preparation and we selected the cen-tral area after skin preparation.Rabbits in the group A, B and C were made into vinorelbine extravasation-induced skin toxic-ity models and rabbits in the group D were injected with normal saline subcutaneously.At the same time, rabbits in the group A were given compound rhubarb preparation hot pack and coated.Group B were given lidocaine ＋dexamethasone ＋normal saline ringlike subcutaneous local injection.One week after modeling, we killed the animals and got the skin and subcutane-ous tissues of the modeling area to do pathological observation.We selected 7 rabbits, each with intact skin administration ar-ea, broken skin administration area and intact skin control area and broken skin control area.Administration area were ad-ministered with smear rhubarb tincture and control area coated with pure water.After 1, 12, 24, 48 and 72 h, we observed the skin irritation situation, respectively.Results Seven days after modeling, in the group A , 4 rabbits had skin toxicity ofⅠ°, 3 rabbits hadⅡ°;in the group B, 5 rabbits hadⅠ°and 2 rabbits hadⅡ°;in the group C, 2 rabbits hadⅡ°, 4 rabbits hadⅢ°and 1 rabbit hadⅣ°;in the group D, 4 rabbits hadⅠ°.Significant difference was found in the skin toxicity degree be-tween group A, B and group C （all P〈0.01）.Compared with group C, the pathological changes of subcutaneous tissue in the group A and group B improved significantly, and the difference was small as compared with that of group D.After one-hour administration to rabbits＇broken skin, the average score of skin irritation was 1.5 points, which belonged to light irrita-tion and after average score was 0.0-0.4, which belonged to non-irritation.Conclusion Compound rhubarb preparation can reduce the skin toxicity caused by vinorelbine extravasation and has little irritation to skin.