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[目的]了解组蛋白去乙酰化酶1(HDAC1)在燃煤污染型砷中毒患者血液及皮肤组织中的转录及表达,探讨其在砷中毒发生、发展乃至癌变中的作用。[方法]在贵州省燃煤污染型地方性砷中毒病区,选择68例地方性砷中毒(以下简称“砷中毒”)确诊患者(轻度24例、中度28例、重度16例)为研究对象,其中40例经过皮肤病理学诊断,分为一般病变组(20例)、癌前病变组(14例)及癌变组(6例)。在距病区约12km的非砷暴露村,选择23例居民作为对照组。在知情同意的原则下,采集上述被调查者的外周血,采用实时荧光定量PCR(FQ-PCR)检测血中HDAC1m RNA的表达。另收集自愿接受手术治疗的61例砷中毒患者皮肤组织标本(一般病变34例、癌前病变21例,癌变6例)和15例正常皮肤组织标本,采用免疫组织化学(IHC)法检测砷中毒患者皮肤及对照皮肤组织中HDAC1蛋白的表达。[结果]HDAC1m RNA在对照组及轻、中、重度砷中毒患者外周血中表达的平均值分别为0.44457(0.37093~0.63904)、0.49286(0.08018~1.12747)、0.45185(0.24413~0.87641)和0.56676(0.30678~0.84471),差异无统计学意义(χ2=1.099,P>0.05);HDAC1m RNA在一般病变组、癌前病变组和癌变组患者外周血中表达的平均值分别为0.32081(0.16723~0.83972)、0.50552(0.28280~1.43397)和0.80479(0.92123~1.89946),差异无统计学意义(χ2=1.982,P>0.05)。HDAC1蛋白在一般病变组、癌前病变组以及癌变组阳性表达率分别为100%、100%和83.33%,与对照组(46.67%)比较表达增强(P<0.01)。[结论]HDAC1参与了砷中毒的发生发展,其蛋白表达增强可能是砷中毒发生的早期事件。
[Objective] To understand the transcription and expression of histone deacetylase 1 (HDAC1) in the blood and skin tissues of coal-burning arsenism patients and to explore the role of HDAC1 in the occurrence, development and carcinogenesis of arsenism. [Method] A total of 68 cases of endemic arsenism (hereinafter referred to as “arsenic poisoning”) were selected in the endemic arsenism area in Guizhou Province (24 mild cases, 28 moderate cases and 16 severe cases ) Were included in this study. Forty cases of them were diagnosed by pathology. They were divided into general lesion group (20 cases), premalignant lesion group (14 cases) and cancerous group (6 case). In the non-arsenic exposed village about 12 km away from the ward, 23 residents were selected as the control group. Under the condition of informed consent, the peripheral blood of the respondents was collected and the expression of HDAC1m RNA in blood was detected by real-time fluorescence quantitative PCR (FQ-PCR). A total of 61 cases of arsenic poisoning patients were randomly selected from the skin tissue samples (34 cases of general lesions, 21 cases of precancerous lesions, 6 cases of carcinogenesis) and 15 cases of normal skin tissue samples. Immunohistochemical (IHC) HDAC1 protein expression in patient’s skin and control skin. [Results] The average expression of HDAC1m RNA in the control group and the peripheral blood of patients with mild, moderate and severe arsenism were 0.44457 (0.37093 ~ 0.63904), 0.49286 (0.08018 ~ 1.12747), 0.45185 (0.24413 ~ 0.87641) and 0.56676 ~ 0.84471). There was no significant difference between the two groups (χ2 = 1.099, P> 0.05). The average expression of HDAC1mRNA in peripheral blood of patients with general lesion, precancerous lesion and cancerous group were 0.32081 (0.16723-0.83972) 0.50552 (0.28280 ~ 1.43397) and 0.80479 (0.92123 ~ 1.89946), the difference was not statistically significant (χ2 = 1.982, P> 0.05). The positive rates of HDAC1 protein in normal, precancerous and cancerous groups were 100%, 100% and 83.33%, respectively, which were significantly higher than those in control group (46.67%) (P <0.01). [Conclusion] HDAC1 participates in the occurrence and development of arsenic poisoning, and the enhanced expression of HDAC1 may be an early event of arsenic poisoning.