复方非交联透明质酸不同给药模式对小鼠皮肤的作用和机制探讨  

Effects and Mechanisms of Compound Non-cross-linked Hyaluronic Acid by Different Delivery Methods on Mouse Skin

作　　者：毕雪婵 谢孟谚 吴艳[1] BI Xuechan;XIE Mengyan;WU Yan(Department of Dermatology&STD,Peking University First Hospital,National Clinical Research Center For Skin and Immune Diseases,Beijing Key Laboratory of Molecular Diagnosis on Dermatoses,NMPA Key Laboratory for Quality Control and Evaluation of Cosmetics,Beijing 100034,China)

机构地区：[1]北京大学第一医院皮肤性病科,国家皮肤与免疫疾病临床医学研究中心,皮肤病分子诊断北京市重点实验室,国家药品监督管理局化妆品质量控制与评价重点实验室,北京100034

出　　处：《中国美容医学》2022年第11期106-111,共6页Chinese Journal of Aesthetic Medicine

摘　　要：目的:观察复方非交联透明质酸通过滚针后涂抹、真皮内注射、联合真皮内注射和滚针后涂抹等不同给药方式对小鼠皮肤生理指标和组织病理的改变,探究非交联透明质酸不同给药模式对皮肤的作用和可能的作用机制。方法:C57BL/6小鼠随机分为3组,每组小鼠两侧皮肤接受不同处理,共6个处理组:CNCLHA真皮注射组(真皮内注射复方非交联透明质酸),CNCLHA真皮注射联合滚针涂抹组(注射联合滚针涂抹复方非交联透明质酸),CNCLHA滚针涂抹组(滚针涂抹复方非交联透明质酸),0.9%生理盐水滚针涂抹组(滚针涂抹0.9%生理盐水),0.9%生理盐水注射组(注射0.9%生理盐水),空白对照组(不做任何处理)。在给药前、第7、14天进行注射和滚针治疗,在给药前和第28天检测小鼠皮肤生理指标[角质层含水量、皮肤弹性、经皮水分丢失(Transepidermalwaterloss,TEWL)],第28天取小鼠皮肤进行组织病理,以及Westernblot和RT-PCR研究,观察Ⅰ型胶原和α-平滑肌肌动蛋白(α-SMA)在蛋白和基因水平的变化。结果:与基线(空白对照组)相比,第28天CNCLHA真皮注射联合滚针涂抹组和CNCLHA滚针涂抹组角质层含水量、弹性升高,TEWL降低,CNCLHA真皮注射组仅弹性升高,TEWL降低,差异有统计学意义(P<0.05)。组织病理及特染结果示滚针治疗组均有表皮增厚;CNCLHA真皮注射组、CNCLHA真皮注射联合滚针涂抹组、CNCLHA滚针涂抹组均有不同程度的真皮增厚,胶原纤维、弹力纤维增生;CNCLHA真皮注射组、CNCLHA真皮注射联合滚针涂抹组透明质酸增多,其中CNCLHA真皮注射联合滚针涂抹组在各方面改善均最明显。Westernblot示与空白对照组相比,第28天CNCLHA真皮注射组、CNCLHA真皮注射联合滚针涂抹组、CNCLHA滚针涂抹组、0.9%生理盐水滚针涂抹组、0.9%生理盐水注射组Ⅰ型胶原蛋白增多,CNCLHA真皮注射组、CNCLHA真皮注射联合滚针涂抹组、CNCLHA滚针涂抹组、0.9%生Objective To observe the skin physiological and histopathology changes of mice after receiving compound non-crosslinked hyaluronic acid(CNCLHA)by diff erent treatments,such as microneedling,dermal injection and combined treatment,and to study possible mechanisms behind diff erent delivery methods.Methods C57BL/6 mice were randomly divided into 3 groups,each group received different treatments on both sides of the skin,thus total for 6 treatment groups:CNCLHA dermal injection group(intradermal injection of compound non crosslinking hyaluronic acid),CNCLHA dermal injection combined with needle roller application group(injection combined with needle roller application of compound non crosslinking hyaluronic acid),CNCLHA needle roller application group(needle roller application of compound non crosslinking hyaluronic acid),0.9%saline needle roller application group(needle roller application of 0.9%saline),0.9%saline injection group(injection of 0.9%saline)and blank control group(without any treatment).The treatments were performed on the day 0,7 and 14,and the skin physiological indexes(water content of the stratum corneum,skin elasticity,and transepidermal water loss)of mice were detected on the day 0 and 28.The skin of mice was collected on the day 28 to perform histopathology,Western blot and RT-PCR study.Results Compared with the baseline(blank control group),on the 28th day,the water content and elasticity of the cuticle in CNCLHA dermal injection combined with needle roller application group,and CNCLHA needle roller application group increased,and TEWL decreased,the diff erences were statistically signifi cant(P<0.05).In CNCLHA dermal injection group,only elasticity increased,but TEWL decreased(P<0.05).Histopathology results showed epidermal thickening in the microneedling groups.Dermal thickening with increased stain of collagen fi bers and elastic fi bers were observed in CNCLHA dermal injection group,CNCLHA dermal injection combined with needle roller application group and CNCLHA needle roller application gr

关 键 词：非交联透明质酸 皮肤生理指标 机制 Ⅰ型胶原蛋白 Α-平滑肌肌动蛋白 

分 类 号：R96[医药卫生—药理学]