饮水型砷暴露人群甲状腺激素受体mRNA的表达及意义

Expression and significance of thyroid hormone receptors mRNA of residents exposed to arsenic via drinking water

目的观察不同水平砷暴露对人群甲状腺激素受体（thyroidhormonereceptors，TRs）mRNA表达的影响，探讨砷的内分泌干扰效应。方法采用分子流行病学调查方法，在饮水型地方性砷中毒病区。依据饮水砷含量的不同分为对照组（〈10wg／L）、低剂量组（10-〈100μg／L）、中剂量组（100-〈200μg／L）、高剂量组（≥200μg／L）；按性别分层后共抽取调查对象273人（对照组、低剂量组、中剂量组、高剂量组分别为58、49、66、100人），开展问卷调查、尿砷测定及心电图检查。同时采用实时荧光定量PCR技术．检测其血液TRsmRNA表达水平。结果对照组、低剂量组、中剂量组、高剂量组人群血液甲状腺激素α受体（TRot）mRNA相对表达量分别为（12．2±5．7）×10^-4、（12．2±5．0）×10^-4、（12．3±5．4）×10^-4、（12．2±4．3）×10^-4，组间比较差异无统计学意义（F=0．109，P〉0．05）。各组人群血液甲状腺激素β受体（TRβ）mRNA相对表达量均较低，对照组、低剂量组、中剂量组、高剂量组分别为（5．7±4．1）×10^-6、（8．6±7．6）×10^-6、（6．3±4．2）×10^-6、（6．2±3．8）×10^-6，组间比较差异有统计学意义（F=2．938，P〈0．05）。TRβmRNA相对表达量随水砷含量及尿砷含量的增加均呈倒U型曲线（R。=0．035、0．067，P均〈0．05）。与对照组比较，低剂量组人群血液TR[5mRNA相对表达量升高，差异有统计学意义（P〈0．05）；与低剂量组相比，高剂量组人群血液TRβmRNA相对表达量下降，差异有统计学意义（P〈0．05）。心电图显示，砷致心律失常多表现为窦性心律过缓，对照组、低剂量组、中剂量组、高剂量组心律失常检出率分别为12．1％（7／58）、10．2％（5／49）、13．6％（9／66）、19．4％（19／98），组间比较差异无统计学意义（x2=2．877，P〉0．05）。心率与TRβmRNA相对表达量1g值呈正相关（r=0．218，P〈0．05）。结论慢性砷暴露可干扰人血液TRβmRNA的正常表达，砷致心律失常可能与TR[3mRNA的异常表达有关。

Objective To detect thyroid hormone receptors （TRs） mRNA expression of subjects exposed to different levels of arsenic, to further study the endocrine disturbing effect of arsenic. Methods Molecular epidemiological method was used, in drinking water type of endemic arsenic poisoning areas, which were divided into control （ 〈 10 μg/L）, low （10 - 〈 100 μg/L）, medium （100 - 〈 200 μg/L） and high （≥200 μg/L） dose groups based on the drinking water arsenic concentrations. According to the gender stratification, a total of 273 （control, low, medium and high dose groups were 58, 49, 66, 100, respectively） residents were chosen. To carry out the questionnaire, urine arsenic determination, electrocardiographic examination. Real-time PCR was used to detect blood TRs mRNA expression. Results TRot mRNA relative expression levels in the control, low, medium and high dose groups were （12.2 ± 5.7） × 10^-4, （12.2 ± 5.0） × 10^-4, （12.3 ± 5.4） × 10^-4, （12.2 ± 4.3） × 10^-4, respectively, the differences were not statistically significant （F = 0.109, P 〉 0.05）. TRβ mRNA relative expression levels were all low, the control,low, medium and high dose groups were （5.7 ± 4.1） × 10^-6, （8.6 ± 7.6） × 10^-6, （6.3 ± 4.2） × 10^-6 and （6.2 ± 3.8） × 10^-6 respectively, the differences were statistically significant （F = 2.938, P 〈 0.05）. The levels of TRβ mRNA relative expression changed with increased content of arsenic in water and urine trends in inverse U-shaped curves （R2 = 0.035, 0.067, all P 〈 0.05）. TRβ mRNA relative expression in low dose group was higher than that in control group, the difference was statistically significant （P 〈 0.05）; TRβ mRNA relative expression in high dose group was lower than that in low dose group, the difference was statistically significant （P 〈 0.05）. Arsenic induced arrhythmia which most displayed sinus bradyeardia; the prevalence of arrhythmia in the control, low, medium and high dose groups were 12.1% （7/58）, 10.2% （5/49）, 13.6% （9/66）, 19.4% （19/98）, respectively, the differences were not statistically significant （x2 = 2.877, P 〉 0.05）. Heart rate was positively associated with the level of TRβ mRNA relative expression in lg value （r = 0.218, P 〈 0.05）. Conclusion Chronic arsenic exposure can disturb TRβ mRNA expression; there is a possible relationship between TRβ mRNA abnormal expression and arrhythmia caused by arsenic.