SOD融合蛋白外用对皮肤自然老化的影响  

Effects of Topical SOD-Fusion-Protein on Natural Skin Aging

作　　者：万婷婷 魏兰璎 程艳 薛荣亮[1,4] WAN Tingting;WEI Lanying;CHENG Yan;XUE Rongliang(Department of Anesthesiology,the Second Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710004,China;Department of Anesthesiology,Peking University Third Hospital,Beijing 100191,China;Department of Anesthesiology,Shaanxi Provincial People's Hospital,Xi'an 710068,China;Anesthesia&Comfort Health Center,Xi'an International Medical Center Hospital,Xi'an 710100,China)

机构地区：[1]西安交通大学第二附属医院麻醉科,陕西西安710004 [2]北京大学第三医院麻醉科,北京100191 [3]陕西省人民医院麻醉科,陕西西安710068 [4]西安国际医学中心医院麻醉与舒适化医疗中心,陕西西安710100

出　　处：《中国皮肤性病学杂志》2022年第4期381-390,共10页The Chinese Journal of Dermatovenereology

基　　金：国家自然科学基金(81471131)。

摘　　要：目的探究皮肤外用PTD4-Cu,Zn-SOD融合蛋白(简称SOD融合蛋白)在防治皮肤自然老化过程中的有效性及安全性。方法将SOD融合蛋白乳膏按乳膏中SOD活力浓度分为单乳(0 U/cm^(2))、乳膏A(100 U/cm^(2))、乳膏B(300 U/cm^(2))、乳膏C(900 U/cm^(2)),以单乳、乳膏C作小鼠去毛区皮肤外用干预,观察小鼠涂抹部位皮肤刺激性、致敏性及经皮毒性。健康6周龄昆明小鼠96只,随机分为6组,采用皮下注射D-半乳糖1000 mg/kg连续42 d建立小鼠亚急性衰老模型,空白对照组(N组)皮下注射等体积的生理盐水。除N组、模型对照组(M组),余4组空白基质组(BM组),低剂量组(LD组),中剂量组(MD组),高剂量组(HD组)涂抹单乳、乳膏A、B、C于小鼠背部脱毛区,封闭6 h后清除残余,连续28 d后,每组取8只小鼠处死,观察脱毛区皮肤组织结构、SOD活性、MDA浓度以及弹性蛋白与胶原蛋白Ⅰ含量的改变,余小鼠继续D-半乳糖干预至42 d,标本留取同上。采用SPSS23.0对实验数据进行分析。结果(1)外用安全性试验中,以900 U/cm^(2)活性浓度涂抹SOD融合蛋白乳膏,并未发现小鼠皮肤有红斑、水疱等致敏及刺激症状。经皮毒性试验中,涂抹单乳及乳膏C两组未出现小鼠死亡,且两组的血液学、血生化、脏器质量等指标差异无统计学意义(P>0.05)。(2)在自然老化试验中,与BM组相比,MD组、HD组小鼠皮毛浓密发亮、顺滑,皮肤结构清晰完整,真皮层明显增厚,且皮肤中MDA含量降低,SOD活力升高,真皮层弹性蛋白表达量增加(P<0.05)。结论SOD融合蛋白乳膏在以900 U/cm^(2)活性浓度涂抹下,具有较好的外用安全性。持续使用300 U/cm^(2)的SOD融合蛋白乳膏,可有效改善小鼠表皮变薄、真皮结缔组织排列紊乱、纤维断裂等问题,可为临床上与年龄相关的皮肤老化及疾病的防治提供新的方法。Objective To investigate the effectiveness and safety of skin topical PTD4-Cu,Zn-SOD fusion protein(referred to as SOD-fusion-protein)in the prevention and treatment of natural skin aging process.Methods The SOD-fusion-protein cream was divided into simple cream(0 U/cm^(2)),cream A(100 U/cm^(2)),B(300 U/cm^(2))and C(900 U/cm^(2))according to the activity concentration of SOD in the cream.The skin irritation,sensitization and transdermal toxicity of the applied area of mice were observed by using simple cream and cream C as external intervention.A total of 96 healthy 6-week-old Kunming mice were randomly divided into 6 groups.Except normal group(N group),subacute aging model of mice was established by subcutaneous injection of D-galactose 1000 mg/kg for 42 d.Group N was injected with an equal volume of normal saline subcutaneously.In addition to N group and model group(M group),blank matrix group(BM group),low-dose group(LD group),medium-dose group(MD group)and high-dose group(HD group)were smeared with simple cream,cream A,B and C on the depilation area on the back of the mice,and then the residue was removed after blocking for 6 h.After 28 consecutive days,8 mice from each group were killed,and the structural changes,SOD activity,MDA concentration and the content of elastin and collagen Ⅰ in the skin of the smear area were observed.The other mice continued with D-galactose intervention until 42 d.Ditto for specimen retention.SPSS23.0 was used to analyze the experimental data.Results(1)In the external safety test,sensitization or irritation symptoms such as erythema and blisters were not found on the mice skin by using the topical SOD-fusion-protein cream(900 U/cm^(2)).In the percutaneous toxicity test,there was no death in the simple cream and cream C groups,and there was no statistically significant difference in hematology,blood biochemistry,and organ mass between the two groups(P>0.05).(2)Compared with BM group,mice in MD group and HD group had thick,shiny and smooth fur,with clear and complete skin structu

关 键 词：皮肤 PTD4-Cu Zn-SOD 自由基 抗老化 安全性 

分 类 号：R751.05[医药卫生—皮肤病学与性病学]