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中华损伤与修复杂志(电子版) ›› 2019, Vol. 14 ›› Issue (04) : 263 -269. doi: 10.3877/cma.j.issn.1673-9450.2019.04.005

所属专题： 文献；

论著

n-3多不饱和脂肪酸在预防皮肤光老化中的作用
朱美抒1, 程飚2, 庞梦如2, 范锟铻1, 韩艳丽1, 姜宏1, 杨光3,†()   
  1. 1. 518035　深圳市第二人民医院烧伤整形科
    2. 510010　广州，解放军南部战区总医院烧伤整形科
    3. 518055　清华大学深圳国际研究生院深圳市卫生科技重点实验室
  • 收稿日期:2019-06-24 出版日期:2019-08-01
  • 通信作者: 杨光
  • 基金资助:
    国家自然科学基金(81671924，81272105)

Role of n-3 polyunsaturated fatty acids in preventing skin photoaging

Meishu Zhu1, Biao Cheng2, Mengru Pang2, Kunwu Fan1, Yanli Han1, Hong Jiang1, Guang Yang3,†()   

  1. 1. Department of Burns and Plastic Surgery, Shenzhen Second People′s Hospital, Shenzhen 518035, China
    2. Department of Burns and Plastic Surgery, General Hospital of Southern Theater Command, People′s Liberation Army, Guangzhou 510010, China
    3. Shenzhen Key Laboratory of Health Sciences and Technology, Tsinghua Shenzhen International Graduate School, Shenzhen 518055, China
  • Received:2019-06-24 Published:2019-08-01
  • Corresponding author: Guang Yang
  • About author:
    Corresponding author: Yang Guang, Email:
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引用本文：

朱美抒, 程飚, 庞梦如, 范锟铻, 韩艳丽, 姜宏, 杨光. n-3多不饱和脂肪酸在预防皮肤光老化中的作用[J]. 中华损伤与修复杂志(电子版), 2019, 14(04): 263-269.

Meishu Zhu, Biao Cheng, Mengru Pang, Kunwu Fan, Yanli Han, Hong Jiang, Guang Yang. Role of n-3 polyunsaturated fatty acids in preventing skin photoaging[J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2019, 14(04): 263-269.

目的

探讨n-3多不饱和脂肪酸(n-3 PUFA)在预防皮肤光老化中的作用。

方法

将8月龄雌性C57BL/6小鼠按照随机数字表法分成2组，n-3 PUFA组和对照组。n-3 PUFA组小鼠除正常饮食外，每日喂食100 μL富含n-3 PUFA [18%二十碳五烯酸(EPA)和12%二十二碳六烯酸(DH)]的鱼油，喂食1个月后对小鼠背部进行脱毛，再以最小红斑剂量的紫外线B对小鼠进行(70 mJ/cm2)照射处理，每周3次，每次20 s，持续1个月。对照组仅同法照射，不喂食n-3 PUFA。实验结束后观察2组小鼠的背部皮肤变化，包括皮肤黑色素沉积灰度和皮纹宽度；用逆转录-聚合酶链反应对黑色素细胞诱导转录因子(MITF)mRNA表达量进行检测；小鼠背部皮肤组织做切片，再用天狼猩红染液进行染色观察，计算皮肤组织厚度；测量胶原蛋白含量；用实时荧光定量检测炎症巨噬细胞相关因子单核细胞趋化蛋白(MCP)-1和肿瘤坏死因子(TNF)-α的表达，以及胶原蛋白Ⅰ、胶原蛋白Ⅲ、细胞外基质金属蛋白酶(MMP)-2、MMP-9表达。数据比较采用Student′s t检验。

结果

n-3 PUFA组小鼠皮肤黑色素沉积灰度值为0.87±0.39，明显低于对照组2.25±0.45，差异有统计学意义(t＝2.28，P<0.05)；n-3 PUFA组MITF mRNA表达量为0.89±0.02，也明显低于对照组1.00±0.03，差异有统计学意义(t＝2.33，P<0.05)；对照组的皮纹相比n-3 PUFA组更加混乱；n-3 PUFA组皮纹宽度为9.65±0.68，对照组皮纹宽度为14.30±0.73，2组比较差异有统计学意(t＝4.65，P<0.05)；经天狼猩红染液染色观察到，n-3 PUFA组的皮肤厚度为(218.40±20.40)×102 μm，明显高于对照组(131.60±15.99)×102 μm，差异有统计学意义(t＝3.35，P<0.05)；n-3 PUFA组胶原蛋白含量(13.90±0.99) mg/g，高于对照组(10.45±0.44) mg/g，差异有统计学意义(t＝3.18，P<0.05)；n-3 PUFA组胶原蛋白Ⅰ表达量1.29±0.09，高于对照组0.98±0.09，差异有统计学意义(t＝2.19，P<0.05)，而2组胶原蛋白Ⅲ表达差异不明显，差异无统计学意义(t＝1.01，P＝0.32)。n-3 PUFA组炎症巨噬细胞相关因子MCP-1和TNF-α的表达为0.74±0.06、0.67±0.06，低于对照组1.00±0.09、1.00±0.06，2组比较差异有统计学意义(t＝2.25、3.51，P值均小于0.05)；n-3 PUFA组MMP-2和MMP-9的相对值为0.58±0.04、0.74±0.05，均低于对照组1.00±0.06、1.00±0.05，2组比较差异有统计学意义(t＝5.09、3.24，P值均小于0.05)。

结论

n-3 PUFA通过增加胶原蛋白合成、降低巨噬细胞浸润和其表达的MMP来抵抗皮肤光老化，具有潜在临床应用价值。

关键词: 脂肪酸类，不饱和, 皮肤, 紫外线, 光老化, 基质金属蛋白酶
Objective

To investigate the effect of n-3 polyunsaturated fatty acid (n-3 PUFA) on preventing skin photoaging.

Methods

Eight-month-old C57B1/6 female mice were divided into two groups, n-3 PUFA group and control group. In the n-3 PUFA group, 100 μL of fish oil rich in n-3 PUFA eicosapentaenoic acid [18% eicosapentaenoic acid (EPA) and 12% decosahexaenoic acid (DHA)] was fed daily, and the backs of the mice were depilated after 1 month of feeding, and then the mice were subjected to ultraviolet B (70 mJ/cm2) irradiation treatment, minimum erythema dose, 3 times a week and each time for 20 s, for 1 month. The control group only irradiated and did not feed n-3 PUFA. At the end of the experiment, the back skin changes of the two groups of mice were observed, including grayscale of skin melanin deposition and the width of the skin; the expression of the melanocyte inducing transcription factor (MITF) mRNA was verified by reverse transcription-polymerase chain reaction. Tissues of the back skin of mice were fixed with paraffin, and then sectioned with sirius red. The thickness of skin tissue was calculated and the collagen content was measured. The expression of inflammatory macrophage related factors monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor (TNF)-α was measured by reverse transcription-polymerase chain reaction. And the expression of collagen Ⅰ, collagen Ⅲ, extracellular matrix metalloproteinase (MMP)-2, MMP-9. Data comparisons were performed using Student′s t-test.

Results

The grayscale of skin melanin deposition of n-3 PUFA group was 0.87±0.39, which was significantly lower than that of the control group (2.25±0.45), the difference was statistically significant (t=2.28, P<0.05). The expression of MITF mRNA in the n-3 PUFA group was 0.89±0.02, which was also significantly lower than that in the control group (1.00±0.03), the difference was statistically significant (t=2.33, P<0.05). After examination, the skin texture of the control group was more confusing than the n-3 PUFA group; the width of the n-3 PUFA group was 9.65±0.68, and the width of the control group was 14.30±0.73, the difference between the two groups was statistically significant (t=4.65, P<0.05). Observed by sirius red staining, the skin thickness of the n-3 PUFA group was (218.40±20.40) μm, which was significantly higher than that of the control group [(131.60±15.99) μm], the difference was statistically significant (t=3.35, P<0.05). The collagen content of n-3 PUFA group [(13.90±0.99) mg/g] was higher than that of the control group [(10.45±0.44) mg/g], the difference was statistically significant (t=3.18, P<0.05); The expression of collagen Ⅰ in the n-3 PUFA group was 1.29±0.09, which was higher than that in the control group (0.98±0.09), the difference was statistically significant (t=2.19, P<0.05), but there was no statistically significant difference in the expression of collagen Ⅲ in the two groups (t=1.01, P=0.32). The expression of inflammatory macrophage-associated factors MCP-1 and TNF-α in the n-3 PUFA group were 0.74±0.06 and 0.67±0.06, which were lower than those of the control group 1.00±0.09, 1.00±0.06, the differences between the two groups were statistically significant (t=2.25, 3.51; with P values below 0.05); the expression levels of MMP-2 and MMP-9 in n-3 PUFA group were 0.58±0.04, 0.74±0.05, which were louer than those of the control group (1.00±0.06, 1.00±0.05), the differences were statistically significant between the two groups (t=5.09, 3.24, with P values below 0.05).

Conclusion

n-3 PUFA ameliorated photoaging through increasing collagen synthesis, decreasing macrophage infiltration and MMPs expression levels, it has potential clinical application value.

Key words: Fatty acids, unsaturated, Skin, Ultraviolet rays, Photoaging, Matrix metalloproteinase
表1 实时荧光定量检测所用引物
引物名称 正向 反向
MITF 5′-CGCCTGATCTGGTGAATCG-3′ 5′-CCTGGCTGCAGTTCTCAAGAA-3′
胶原蛋白Ⅰ 5′-ACGTCCTGGTGAAGTTGGTC-3′ 5′-CAGGGAAGCCTCTTTCTCCT-3′
胶原蛋白Ⅲ 5′-TGGCCCTGACCCAACTATGAT-3′ 5′-GCACTTTTTGCCCTTCTTAATGTT-3′
MCP-1 5′-CCAGCCTACTCATTGGGATCA-3′ 5′-CTTCTGGGCCTGCTGTTCA-3′
TNF-α 5′-ACGTCGTAGCAAACCACCAA-3′ 5′-GCAGCCTTGTCCCTTGAAGA-3′
MMP-2 5′-CAAGTTCCCCGGCGATGTC-3′ 5′-TTCTGGTCAAGGTCACCTGTC-3′
MMP-9 5′-CTGGACAGCCAGACACTAAAG-3′ 5′-CTCGCGGCAAGTCTTCAGAG-3′
GAPDH 5′-AGGTCGGTGTGAACGGATTTG-3′ 5′-GGGGTCGTTGATGGCAACA-3′
表2 2组小鼠紫外线B照射处理1个月后皮肤黑色素沉积灰度、MITF mRNA表达量及皮纹宽度比较(±s)
组别 鼠数 (只) 黑色素沉 积灰度 MITF mRNA表达量 皮纹宽度
对照组 8 2.25±0.45 1.00±0.03 14.30±0.73
n-3 PUFA组 8 0.87±0.39 0.89±0.02 9.65±0.68
t值 ? 2.28 2.33 4.65
P值 ? <0.05 <0.05 <0.05
图1 2组小鼠皮肤相关指标检测情况
图2 2组小鼠天狼猩红染液染色情况(×5)
表3 2组小鼠紫外线B照射处理1个月后胶原蛋白Ⅰ、胶原蛋白Ⅲ、MCP－1、TNF－α及MMP－2、MMP－9相对值变化比较(±s)
组别 鼠数(只) 胶原蛋白Ⅰ 胶原蛋白Ⅲ MCP-1 TNF-α MMP-2 MMP-9
对照组 8 0.98±0.09 1.00±0.07 1.00±0.09 1.00±0.06 1.00±0.06 1.00±0.05
n-3 PUFA组 8 1.29±0.09 1.12±0.09 0.74±0.06 0.67±0.06 0.58±0.04 0.74±0.05
t值 ? 2.19 1.01 2.25 3.51 5.09 3.24
P值 ? <0.05 0.32 <0.05 <0.05 <0.05 <0.05
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