皮肤组织蛋白酶D表达与晚期糖基化终末产物堆积的相关性研究 |
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引用本文: | 黄云芬 许庆芳 黎钰莹 许新雅 谢阳 夏悦 万苗坚 陆春 赖维. 皮肤组织蛋白酶D表达与晚期糖基化终末产物堆积的相关性研究[J]. 中华皮肤科杂志, 2018, 51(7): 500-505. DOI: 10.3760/cma.j.issn.0412-4030.2018.07.005 |
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作者姓名: | 黄云芬 许庆芳 黎钰莹 许新雅 谢阳 夏悦 万苗坚 陆春 赖维 |
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作者单位: | 1. 中山大学附属第三医院2. 中山大学附属第三医院皮肤科3. 广州中山大学第三医院皮肤科4. 广州中山大学附属第三医院皮肤科 |
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基金项目: | 国家自然科学基金;广东省自然科学基金 |
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摘 要: | 目的 研究组织蛋白酶D(CatD)与晚期糖基化终末产物(AGE)在不同年龄、不同曝光程度皮肤中的表达及其相关性,初步探讨CatD在光老化皮肤AGE降解和堆积中的作用。方法 15 ~ 20岁、35 ~ 40岁、55 ~ 60岁及75 ~ 80岁患者曝光和非曝光部位皮肤组织,共8组,每组6份。采用免疫组化和免疫荧光双染法分别检测CatD和AGE在各组皮肤中的表达。采用析因设计方差分析、Wilcoxon秩和检验和Kruskal?Wallis秩和检验分析CatD和AGE表达与年龄、曝光的关系,并用Pearson相关系数分析CatD和AGE两者表达的相关性。结果 免疫组化显示,CatD表达随年龄增加而明显下降,而AGE的沉积则随年龄增加而逐渐增多;曝光部位CatD表达较同年龄组非曝光部位明显降低,而AGE沉积比同年龄组非曝光部位明显升高。析因设计方差分析显示,曝光会降低CatD的表达(F = 58.70,P < 0.001),但会增加AGE的表达(F = 158.18,P < 0.001)。年龄的增长亦会引起CatD表达降低(F = 79.49,P < 0.001),但AGE表达随年龄的增长而增加(F = 106.06,P < 0.001)。除了15 ~ 20岁年龄组,其他年龄组曝光组和非曝光组间CatD(35 ~ 40岁组:0.020 ± 0.005比0.032 ± 0.005;55 ~ 60岁组:0.012 ± 0.004比0.026 ± 0.002;75 ~ 80岁组:0.002 ± 0.001比0.013 ± 0.004)和AGE平均吸光度值(35 ~ 40岁组:0.030 ± 0.008比0.010 ± 0.003 ;55 ~ 60岁组:0.066 ± 0.010比0.021 ± 0.004 ;75 ~ 80岁组:0.085 ± 0.015比0.035 ± 0.009 )差异均有统计学意义(均P < 0.001)。在固定曝光因素各水平条件下,不同年龄组间CatD和AGE表达差异亦均有统计学意义(均P < 0.001)。免疫荧光双染结果与免疫组化结果相似。Pearson相关分析显示,曝光部位皮肤CatD表达与AGE沉积呈高度负相关(r = -0.915,P < 0.05),在非曝光皮肤中两者呈中度负相关(r = -0.730,P < 0.05)。结论 随年龄增长皮肤组织中CatD表达水平下降,而AGE表达水平上升。非曝光部位皮肤CatD和AGE表达呈中度负相关,曝光部位皮肤CatD和AGE表达呈高度负相关,CatD很可能在光老化皮肤AGE降解和堆积中起重要作用。
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关 键 词: | 皮肤衰老 组织蛋白酶D 糖基化终产物 高级 年龄因素 日光 |
收稿时间: | 2017-08-31 |
Correlation analysis between the of cathepsin D and the accumulation of advanced glycation end products in skin tissues |
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Abstract: | Huang Yunfen, Xu Qingfang, Li Yuying, Xu Xinya, Xie Yang, Xia Yue, Wan Miaojian, Lu Chun, Lai WeiDepartment of Dermatology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, ChinaCorresponding author: Xu Qingfang, Email: xqf69@163.com【Abstract】 Objective To determine the of cathepsin D and advanced glycation end products(AGEs)in skin tissues from patients of different ages or skin tissues with different degrees of sun exposure, to evaluate their correlation, and to preliminarily investigate the role of cathepsin D in the degradation and accumulation of AGEs in photoaged skin. Methods Skin tissues were collected from sun-exposed and sun-protected body sites in patients aged 15 - 20 years, 35 - 40 years, 55 - 60 years or 75 - 80 years. These skin tissues were divided into 8 groups according to age of patients and degrees of sun exposure, and there were 6 specimens in each group. Immunohistochemical and immunofluorescent methods were used to measure the of cathepsin D and AGEs in the skin tissues. Statistical analysis was carried out by factorial design analysis of variance, Wilcoxon rank sum test and Kruskal-Wallis rank sum test for analyzing associations of the of cathepsin D and AGEs with age and sun exposure, as well as by Pearson correlation analysis for assessing the correlation between cathepsin D and AGEs . Results Immunohistochemical study showed that the of cathepsin D markedly decreased along with the increase of age, but the accumulation of AGEs gradually increased along with the increase of age. In the same age group, the cathepsin D was lower in the sun-exposed skin tissues than in the sun-protected skin tissues, while the accumulation of AGEs was more in the sun-exposed skin tissues than in the sun-protected skin tissues. Factorial design analysis of variance showed that sun exposure could decrease the of cathepsin D (F = 58.70, P < 0.001), but increase the accumulation of AGEs (F = 158.18, P < 0.001). Moreover, the increase of age could lead to decreased of cathepsin D (F = 79.49, P < 0.001), and increased of AGEs (F = 106.06, P < 0.001). Compared with the sun-protected skin tissues, the sun-exposed skin tissues in all the age groups showed significantly lower absorbance value of cathepsin D (35 - 40 years: 0.020 ± 0.005 vs. 0.032 ± 0.005; 55 - 60 years: 0.012 ± 0.004 vs. 0.026 ± 0.002; 75 - 80 years: 0.002 ± 0.001 vs. 0.013 ± 0.004; all P < 0.001), but higher absorbance value of AGEs (35 - 40 years: 0.030 ± 0.008 vs. 0.010 ± 0.003; 55 - 60 years: 0.066 ± 0.010 vs. 0.021 ± 0.004; 75 - 80 years: 0.085 ± 0.015 vs. 0.035 ± 0.009; all P < 0.001) except the age group of 15 - 20 years. No matter whether the skin tissues were sun-exposed or sun-protected, there were significant differences in the of cathepsin D and AGEs among different age groups (all P < 0.001). The results of double immunofluorescence staining were similar to those of immunohistochemical study. Pearson correlation analysis showed that the of cathepsin D in the sun-exposed skin tissues was highly negatively correlated with the accumulation of AGEs (r = -0.915, P < 0.05), while they were moderately negatively correlated in the sun-protected skin tissues (r = -0.730, P < 0.05). Conclusions Along with the increase of age, the of cathepsin D in skin tissues decreased, but the of AGEs increased. In the sun-protected skin tissues, the of cathepsin D was moderately negatively correlated with the of AGEs, while they were highly negatively correlated in the sun-exposed skin tissues, suggesting that cathepsin D may play an important role in the degradation and accumulation of AGEs in photoaged skin. |
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Keywords: | Skin aging Cathepsin D Glycosylation end products advanced Age factors Sunlight |
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