茶多酚调节AMPK/SIRT1/PGC-1信号通路对光老化小鼠模型氧化损伤的影响  

Effect of tea polyphenol on oxidative damage in a photoaging mouse model by regulating AMPK/SIRT1/PGC-1 signaling pathway

作　　者：陈颖[1] 赵菊花 杨羽 王洁 杜秀君 刘海霞 CHEN Ying;ZHAO Juhua;YANG Yu;WANG Jie;DU Xiujun;LIU Haixia(Department of Dermatology,Beijing Anzhen Nanchong Hospital of Capital Medical University,Nanchong Central Hospital,Nanchong 637000,Sichuan,China)

机构地区：[1]首都医科大学附属北京安贞医院南充医院·南充市中心医院皮肤科,四川南充637000

出　　处：《西部医学》2025年第2期205-211,共7页Medical Journal of West China

基　　金：南充市科技项目(20SXQT0116)。

摘　　要：目的 探讨茶多酚(TP)调节单磷酸腺苷活化蛋白激酶(AMPK)/沉默信息调节因子1(SIRT1)/过氧化物酶体增殖物激活受体γ共激活因子1(PGC-1)信号通路对光老化小鼠模型氧化损伤的影响。方法 采用皮下注射D-半乳糖联合紫外线(UVA+UVB)照射构建光老化小鼠模型,将造模成功小鼠按照随机数字表法分为模型组、TP低、中、高剂量组(50、100、150 mg/kg)、阳性对照组(维生素E 30 mg/kg),每组12只,另选12只作对照组在正常光照饲养,各组灌胃相应药物,1次/d,连续30 d,给药结束后对各组小鼠进行皮肤皱纹等级评分;HE、Masson染色观察小鼠皮肤组织病理损伤、表皮层厚度及纤维化程度;免疫组化法测定Ⅰ型胶原蛋白(COL-Ⅰ)、Ⅲ型胶原蛋白(COL-Ⅲ)的表达;酶生化法测定皮肤组织中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、羟脯氨酸(Hyp)及丙二醛(MDA)水平;酶联免疫吸附测定(ELISA)法检测小鼠皮肤组织IL-6、IL-1β、肿瘤坏死因子α(TNF-α)水平;蛋白免疫印迹法(Western blot)检测基质金属蛋白酶-1(MMP-1)、MMP-9、AMPK/SIRT1/PGC-1信号通路蛋白表达。结果 与对照组相比,模型组小鼠皮肤评分、表皮层厚度、MDA、IL-6、IL-1β、TNF-α水平、MMP-1、MMP-9表达显著升高,胶原蛋白含量、SOD、CAT、Hyp水平、COL-Ⅰ、COL-Ⅲ、p-AMPK/AMPK、SIRT1、PGC-1表达显著降低(均P<0.05);与模型组相比,TP低、中、高剂量组及阳性对照组小鼠皮肤评分、表皮层厚度、MDA、IL-6、IL-1β、TNF-α水平、MMP-1、MMP-9表达显著降低,胶原蛋白含量、SOD、CAT、Hyp水平、COL-Ⅰ、COL-Ⅲ、p-AMPK/AMPK、SIRT1、PGC-1表达显著升高(均P<0.05)。结论 TP可能通过激活AMPK/SIRT1/PGC-1信号通路,抑制氧化应激,对D-半乳糖联合UVA+UVB辐射诱导的皮肤老化具有改善作用。Objective To investigate the effect of tea polyphenol(TP) on oxidative damage in a photoaging mouse model by regulating adenosine monophosphate-activated protein kinase(AMPK)/silent mating type information regulation 2 homolog 1(SIRT1)/peroxisome proliferator-activated receptor γ coactivator-l(PGC-1) signaling pathway.Methods A photoaging mouse model was constructed by subcutaneous injection of D-galactose combined with ultraviolet(UVA+UVB) irradiation,successfully modeled mice were randomly grouped into model group,TP low,medium,and high dose groups(50,100,150 mg/kg),and positive control group(vitamin E 30 mg/kg) using a random number table method,with 12 mice in each group,another 12 mice were selected to be fed under normal light as the control group,each group was given corresponding medication,gavage once a day for 30 consecutive days.After the administration,mice in each group was evaluated for skin wrinkle grading;HE and Masson staining were applied to observe the pathological damage,epidermal layer thickness,and fibrosis degree of mouse skin tissue;immunohistochemical method was applied to measure the expression of type Ⅰ collagen(COL-Ⅰ) and type Ⅲ collagen(COL-Ⅲ);enzyme biochemical method was applied to measure the levels of superoxide dismutase(SOD),catalase(CAT),hydroxyproline(Hyp),and malondialdehyde(MDA) in skin tissue;enzyme linked immunosorbent assay(ELISA) was applied to detect the levels of interleukin-6,interleukin-1β(IL-6,IL-1β),and tumor necrosis factor-α(TNF-α) in mouse skin tissue;Western blot was applied to detect the expression of matrix metalloproteinase-1,-9(MMP-1,MMP-9),and AMPK/SIRT1/PGC-1 signaling pathway proteins.Results Compared with the control group,the skin score,epidermal layer thickness,MDA,IL-6,IL-1β,TNF-α levels,and MMP-1 and MMP-9 expression of mice in the model group were obviously increased,the collagen content,SOD,CAT,Hyp levels,COL-Ⅰ,COL-Ⅲ,p-AMPK/AMPK,SIRT1,and PGC-1 expression were obviously reduced(P<0.05);compared with the model group,the skin scor

关 键 词：茶多酚 单磷酸腺苷活化蛋白激酶/沉默信息调节因子1/过氧化物酶体增殖物激活受体γ共激活因子1 光老化 氧化损伤 

分 类 号：R758.14[医药卫生—皮肤病学与性病学]