槲皮素对中波紫外线诱导的黄褐斑模型豚鼠皮肤黑色素合成的影响及调控机制  

Effect of quercetin on skin melanin synthesis in guinea pigs with UVB-induced melasma and its regulatory mechanism

作　　者：魏晓歌 杨楠 宋斐[1,2,3] 孙文静 李开颖[1,2,3] 王燕 马惠昇 穆静 WEI Xiaoge;YANG Nan;SONG Fei;SUN Wenjing;LI Kaiying;WANG Yan;MA Huisheng;MU Jing(School of Traditional Chinese Medicine,Ningxia Medical University,Ningxia Yinchuan 750004,China;Ningxia Medical University Key Laboratory of Ningxia Minority Medicine Modernization Ministry of Education,Ningxia Yinchuan 750004,China;Ningxia Regional Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Regional High Incidence Disease,Ningxia Yinchuan 750004,China)

机构地区：[1]宁夏医科大学中医学院,宁夏银川750004 [2]宁夏医科大学宁夏少数民族医药现代化教育部重点实验室,宁夏银川750004 [3]宁夏区域高发病中西医结合防治研究重点实验室,宁夏银川750004

出　　处：《中国医院药学杂志》2023年第24期2715-2721,共7页Chinese Journal of Hospital Pharmacy

基　　金：宁夏自然科学基金项目(编号:2023AAC03158);国家自然科学基金项目(编号:81960893);宁夏医科大学中医学院一流学科建设项目(编号:ZY0019110305)。

摘　　要：目的:探究槲皮素(quercetin, Que)对中波紫外线(ultraviolet B,UVB)诱导的黄褐斑模型豚鼠皮肤黑色素合成的影响及其分子机制。方法:制备高、中、低剂量槲皮素软膏和0.25%熊果苷软膏。将35只雌性豚鼠随机分为空白组,模型组,基质组,槲皮素低、中、高剂量组及熊果苷阳性对照组。空白组不做处理,其余各组均在用药后行总量为6 500 mJ·cm^(-2)的UVB辐照诱导建立黄褐斑豚鼠模型(10 min·d^(-1),隔天一次)。连续治疗36 d后取材,拍照观察豚鼠皮肤颜色变化;HE和Masson-Fontana染色检测皮肤黑色素沉积情况;ELISA检测皮肤组织中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)的表达;免疫组织化学法检测皮肤组织中黑色素合成相关调节因子(MITF、TYR、TYRP1)的表达;Western blot检测皮肤组织中P38MAPK-ERK信号通路关键蛋白(P38MAPK、p-P38MAPK、ERK、p-ERK)及MITF、TYR的蛋白表达。结果:槲皮素能够增加豚鼠皮肤组织中SOD、CAT、GSH-Px的表达(P<0.05)。低剂量槲皮素可减少豚鼠皮肤黑色素沉积,下调MITF、TYR、TYRP1、p-P38MAPK(P<0.05),上调p-ERK表达(P<0.05)。中、高剂量槲皮素可增加豚鼠皮肤黑色素沉积,升高MITF、TYR、TYRP1表达(P<0.05);同时,高剂量槲皮素可上调p-P38MAPK、下调p-ERK表达(P<0.05)。结论:低剂量槲皮素对UVB诱导的黄褐斑模型豚鼠黑色素沉积有一定改善作用,高剂量槲皮素会加重黑色素的沉积,其机制可能与槲皮素双向调节P38MAPK-ERK信号通路关键蛋白及下游黑色素合成相关因子的表达有关。OBJECTIVE To investigate the effect and molecular mechanism of quercetin(Que)on skin melanin deposition in guinea pigs with ultraviolet B(UVB)-induced melasma.METHODS High,medium,and low doses of quercetin ointment and 0.25%arbutin ointment were prepared.Thirty-five female guinea pigs were randomly divided into control group(Normal),Model group,Matrix group,and Que low,middle,high dose groups and Arbutin positive control group.The Normal group was not treated,and the other groups were irradiated with 6500 mJ·cm^(-2) UVB to establish chloasma model in guinea pigs(10 min·d^(-1),once every other day).After 36 days of continuous treatment,the skin color changes of guinea pigs were observed by photographing.HE and Masson-Fontana staining were used to observe skin melanin deposition.ELISA was used to detect the expression of SOD,CAT,GSH-Px in skin tissue.Immunohistochemical method was used to detect the expression of melanin synthesis related regulatory factors(MITF,TYR,TYRP1)in skin tissue of each group.Western blot was used to detect the protein expressions of key proteins of p38MAPK-ERK signaling pathway(P38MAPK,p-P38MAPK,ERK,p-ERK)and MITF,TYR in skin tissue.RESULTS Quercetin increased the expression of SOD,CAT and GSH-Px in guinea pig skin tissue(P<0.05).Low-dose quercetin reduced melanin deposition in guinea pig skin,down-regulated MITF,TYR,TYRP1 and p-p38MAPK expression(P<0.05),and up-regulated p-ERK expression(P<0.05).Quercetin at medium and high doses increased melanin deposition and the expression of MITF,TYR and TYRP1in guinea pig skin(P<0.05).At the same time,the expression of p-p38MAPK was up-regulated and p-ERK was down-regulated in high dose quercetin group(P<0.05).CONCLUSION Low-dose quercetin can improve the melanin deposition in guinea pigs with UVB-induced melasma,while high-dose quercetin can aggravate the deposition of melanin,possibly by regulating the expression of key proteins in the P38MAPK-ERK signaling pathway and downstream melanin synthesis related factors.

关 键 词：槲皮素 黄褐斑 黑色素 酪氨酸酶 小眼畸形相关转录因子 P38MAPK-ERK信号通路 

分 类 号：R285[医药卫生—中药学]