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
Study on the Effect of the Transcription and Expression of Histone Deacetylase 1 in Blood and Skin Tissue of Endemic Arsenism Caused by Coal-burning
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摘要:
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12 km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HDAC1 mRNA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 HDAC1 mRNA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);HDAC1 mRNA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。 Abstract:Objective To investigate the transcription and expression of histone deacetylase 1 (HDAC1) in peripheral blood and skin tissue of endemic arsenism patients, and to study its effects on the development and carcinogenesis of arsenism. Methods Sixty eight arsenism patients (including 24 mild cases, 28 moderate cases and 16 severe cases) were selected from the areas with endemic arsenism in Guizhou province. Among the subjects, 40 cases were diagnosed by pathological measures, and they were divided into general pathological changes (20 cases), precancerous (14 cases) and cancerous group (6 cases). Another 23 persons were selected as control in an area 12 km away from the endemic arsenism area. Under the principle of informed consent, blood samples were collected from all individuals. The mRNA expression of HDAC1 was detected by Real-time quantitative reverse transcription polymerase chain reaction (FQ-PCR). At the same time, skin tissue samples were collected from the voluntary surgical treatment patients with endemic arsenism (total 61 cases, including 34 general pathological changes cases, 21 precancerous cases and 6 cancerous cases)and from some of the control (s 15 cases). HDAC1 protein was detected by immunohistochemical method. Results Average level of HDAC1 mRNA were 0.444 57 (0.370 93~0.639 04), 0.492 86 (0.080 18~1.127 47), 0.451 85 (0.244 13~0.87641) and 0.566 76(0.306 78~0.844 71) respectively among controls, mild, moderate and severe arsenism group, with no significant difference among these groups (χ2=1.099, P > 0.05). The mRNA average level of HDAC1 were 0.320 81 (0.167 23~0.839 72), 0.505 52 (0.282 80~1.433 97) and 0.804 79 (0.921 23~1.899 46) individually among general pathological changes, precancerous and cancerous group respectively, there was no significant difference among these groups ((χ2=1.982, P > 0.05). The expression rates of HDAC1 protein were 100%, 100% and 83.33% among general pathological changes, precancerous and cancerous group separately, compared with the control group (46.67%), the protein expression of the arsenism cases was significantly higher (P < 0.01), and the extent of expression gradually increased with the aggravation of skin damage (rs=0.580, P < 0.01). Conclusion HDAC1 participated the development of the arsenism. High expression of its protein was early events during the process of the arsenism. HDAC1 may be the new target markers for early diagnosis and treatment of arsenism.
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