低剂量中波紫外线照射Nrf2基因缺陷小鼠后诱导晒伤反应的实验研究

Low-dose ultraviolet B induces sunburn reaction in Nrf2 gene-deficient mice

目的观察Nrf2-Keapl通路在保护皮肤免受中波紫外线（UVB）影响中的作用。方法8周龄雌性野生型（即Nrf2＋/＋组）和Nrf2-/-小鼠，每组8只，分别用200mJ／cm2UVB（FL120SE灯）照射小鼠耳朵背侧，用刻度计分别测量UVB照射前和照射后1、2．4、7、9、11、14d小鼠耳朵厚度，记录照射前后两组鼠耳皮肤镜下形态，36h取各组鼠耳标本进行HE染色及TUNEL实验，记录结果并进行统计学分析。结果Nrf2-／-组小鼠耳平均厚度为（0．49±0．22）cm，Nrf2恤为（0．25±0．03）cm，经秩和检验，差异有统计学意义（P〈0．01）。UVB照射小鼠后36h组织学检查，Nrf2-/-组真皮水肿和表皮坏死，淋巴细胞浸润和真皮血管扩张更显著；表皮晒伤细胞数[（17．0±3．9），视野]也较Nrf2＋/＋组[（5．0±1．7），视野]明显，两组差异有统计学意义（P〈0．01）；Nrf2-/-组TUNEL阳性细胞数约是Nrf2嘲的5倍。单一UVB照射Nr￡2斗小鼠较Nrf2m小鼠发生更强烈而持久的晒伤反应。结论Nrf2-Keapl通路可保护皮肤免受UVB的影响，包括由于UVB照射引起的细胞凋亡和氧化损伤。

Objective To investigate the roles of Nrf2-Keapl system in the protection of skin from ultraviolet B （UVB）-induced damage. Methods The dorsal surface of ears of 8 wild-type and 8 nrf2-null mutant 8-week-old female mice was exposed to a single dose of UVB irradiation （200 mJ/em2） by using a FL120SE UV lamp source. Then, the morphology of ears was observed with the measurement of thickness before, as well as on day 1, 2, 4, 7, 9, 11 and 14 after, the irradiation. Biopsy specimens were taken from the ears 36 hours after the irradiation and subjected to hematoxylin and eosin stainiog as well as terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL） assay. The test results were recorded and statistically analyzed by rank sum test and t test. Results A significant increase was observed in the thickness of mouse ears and number of sunburn cells per high-power field （400%） in nrf2-null mutant mice compared with wild-type mice （（0.49±0.22） cmvs. （0.25±0.03） cm, P〈0.01;17.0±3.9vs. 5.0± 1.7, t=13.8, P〈0.01）.The number of TUNEL positive cells in the nrf2-null mutant mice was about 5 times that in the wild mice. The sunburn reaction appeared more intense and persistent in nrf2-null mutant mice than in the wild mice. Conclusion Nrf2- Keapl pathway may protect skin against acute UVB damage, including cell apoptosis and oxidative damage.