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目的观察亚砷酸钠[As9(Ⅲ)]对家兔皮肤组织角蛋白转录的影响,探讨亚慢性砷暴露对皮肤角化的影响。方法将30只健康成年清洁级雄性新西兰大耳兔随机分为5组,每组6只,分别为对照(去离子水)及低[L,0.13mg/(kg体重)]、中(M,0.26mg/kg.w)、中高(MH,0.65mg/kg.w)、高(H,1.30mg/kg.w)剂量亚砷酸钠染毒组。采用自由饮水方式经口染毒,根据家兔日饮水量和体重配制亚砷酸钠水溶液,连续染毒12周后处死家兔,采用皮肤活检术在家兔背部相同位置剖取全厚皮肤按约200mg,采用高效液相色谱-氢化物发生原子荧光光谱法测定各形态砷含量,通过实时荧光定量PCR(Real-Time Quantitative PCR)检测角蛋白1(keratin1,K1)、角蛋白2(keratin2,K2)和角蛋白10(keratin10,K10)mRNA的表达水平。结果从M剂量组开始可观察到染毒组家兔背腹毛发粗糙,以H组尤为明显。皮肤组织K1mRNA表达水平随砷染毒剂量增加呈先上调(L组)再下调的趋势(MH组和H组)(P<0.05);K2mRNA表达水平随砷染毒剂量增加先上调(L组和M组)再下降至正常(MH组和H组)(P<0.05);K10mRNA表达水平在L组上调而在H组下调(P<0.05)。结论亚砷酸钠经口摄入后影响家兔皮肤表皮角蛋白基因的转录,其中低剂量对表皮角蛋白基因转录有促进作用,但随染毒剂量的增加其促进减弱甚至抑制表皮角蛋白基因的转录。提示砷对皮肤的损伤与表皮角蛋白的表达紊乱有关。
Objective To observe the effect of sodium arsenite [As9 (Ⅲ)] on keratin transcription in rabbit skin and explore the effect of subchronic arsenic exposure on keratinization. Methods Thirty healthy adult male New Zealand white rabbits were randomly divided into five groups (n = 6 each): control (deionized water) and low [L, 0.13 mg / (kg body weight) 0.26mg / kg.w), medium high (MH, 0.65mg / kg.w) and high (H, 1.30mg / kg.w). The rats were sacrificed at 12 weeks after exposure to rabbits. Skin biopsy was performed on the same site of the back of rabbits to cut the full thickness of the skin. About 200mg. The contents of arsenic in various forms were determined by high performance liquid chromatography-hydride generation atomic fluorescence spectrometry. The expression of keratin 1 (K1), keratin 2 K2) and keratin 10 (K10) mRNA expression levels. Results From the beginning of the M dose group, the dorsum of the rabbits in the exposed group was rough, especially in the H group. The expression level of K1mRNA in skin tissue increased first (L group) and then decreased (MH group and H group) with the increase of arsenic dose (P <0.05); The expression level of K2 mRNA increased first M group), then decreased to normal group (MH group and H group) (P <0.05). K10 mRNA expression was up-regulated in group L and decreased in group H (P <0.05). Conclusion Sodium arsenite can affect the transcription of keratin genes in rabbits skin after oral ingestion, and the low doses can promote the transcription of epidermal keratin genes. However, as the dose of sodium arsenite increases, the expression of epidermal keratin genes is reduced or even inhibited Of transcription. Tip arsenic damage to the skin and epidermal keratin expression disorders.