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作 者:王首帆[1] 戴杏[1] 雷铁池[1] 徐世正[1]
出 处:《中华皮肤科杂志》2010年第1期25-27,共3页Chinese Journal of Dermatology
基 金:国家自然科学基金(30671897).志谢 Dct基因敲除小鼠由瑞士国家癌症研究所Friedrich Beermannkang博士提供.动物实验部分还得到本科室刘小明和江珊博士的协助
摘 要:目的探讨人抗Ro/SSA血清腹腔注射多巴色素异构酶基因敲除小鼠(Dct^-/-)与野生型C57BL/6J小鼠对慢性UVA照射诱导表皮细胞凋亡的易感性。方法将高滴度人抗Ro/SSA血清间断腹腔注射于Dct^-/-小鼠与野生型C57小鼠,随后给予小鼠慢性UVA照射。每次照射剂量为10J/cm^2,共6次,累计剂量为60J/cm^2。取尾部照射区域皮肤,行石蜡包埋组织切片,经HE染色和TUNEL标记在光镜下分别计数每个视野100个表皮细胞中日晒伤细胞(SBC)数和凋亡细胞数。结果经慢性UVA照射后,抗Ro/SSA血清注射Dct^-/-小鼠SBC数为(14±1.0)/100个表皮细胞,凋亡细胞数为(62±2.7)/100个表皮细胞。血清注射C57野生型小鼠SBC数为(7±0.6)/100个表皮细胞,凋亡细胞数为(30±1.6)/100个表皮细胞,两者比较差异均有统计学意义(P〈0.05)。而未注射血清的Dct^-/-小鼠SBC数为(6±0.9)/100个表皮细胞,凋亡细胞数为(42±2.5)/100个表皮细胞,与注射血清的Dct^-/-小鼠相比差异有统计学意义(P〈0.05)。结论当一定浓度的抗Ro/SSA抗体存在时,表皮黑素细胞Dct基因缺陷能增强慢性UVA诱导的表皮细胞凋亡,可能关系到红斑狼疮患者抗Ro/SSA抗体介导皮肤光敏感性发生。Objective To investigate the susceptibility of epidermal cells to ultraviolet A (UVA)- induced apoptosis in dopachrome tautomerase knockout (Dct^-/-) mice versus wildtype C57BL/6J mice. Methods High titer of anti-Ro/SSA-positive sera collected from three patients with SLE and typical cutaneous photosensitivity were intraperitoneally injected into both Dct^-/- and wildtype mice, which were then chronically exposed to UVA irradiation at a single dose of 10 J/cm^2 three times a week for two weeks. Then, UVA-irradiated tail skin was excised from each mouse, embedded with paraffin, cut into 4 to 5-μm sections followed by hematoxylin/eosin staining and terminal deoxynucleotidyl transferase nick end labeling (TUNEL), respectively, for the counting of sunburn cells (SBC) and apoptotic cells. Results After chronic UVA exposure, the number of SBC and TUNEL-positive cells per 100 epithelial cells was significantly higher in serum-injected Dct^-/-mice than in serum-injected wildtype mice (14 ± 1.0 vs 7 ± 0.6, 62 ± 2.7 vs 30 ± 1.6, both P 〈 0.05). A significant decrease was also observed in the number of SBC (6 ± 0.9 per 100 epithelial cells) and TUNEL-positive cells (42 ± 2.5 per 100 epithelial cells) in uninjected Dct^-/- mice compared with those of serum-injected Det^-/- mice (both P 〈 0.05). Conclusions The deficiency of Dct gene increases the susceptibility of epidermal cells to UVA- induced apoptosis under the presence of anti-Ro/SSA antibody, which potentially contributes to the development of anti-Ro/SSA antibody-mediated photosensitivity in SLE.
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