碘乙酸对大鼠的血液毒性  

Hematological toxicity of disinfection by-product iodoacetic acid

作　　者：牟利 屈家源 赵欢 刘长江 Mou Li;Qu Jiayuan;Zhao Huan;Liu Changjiang(NHC Key Laboratory of Birth Defects and Reproductive Health,Chongqing Population and Family Planning Science and Technology Research Institute,Chongqing 400020,China;Chongqing Medical University,Chongqing 400016,China)

机构地区：[1]重庆市人口和计划生育科学技术研究院/国家卫健委出生缺陷与生殖健康重点实验室,重庆400020 [2]重庆医科大学,重庆400016

出　　处：《卫生研究》2024年第4期553-560,共8页Journal of Hygiene Research

基　　金：重庆市自然科学基金面上项目(No.CSTB2022NSCQ-MSX1666)。

摘　　要：目的明确碘乙酸(iodoacetic acid,IAA)染毒对大鼠血液系统和电解质平衡的影响,并进一步探讨IAA染毒后血常规参数和电解质水平之间的相关性和IAA对血液系统的主要毒性及作用模式。方法选取48只雄性21日龄SPF级SD大鼠,使用不同剂量IAA(0、6.25、12.50和25.00 mg/kg)连续灌胃31天。检测全血血常规参数和血浆无机离子水平,并采用Spearman相关系数评估两者相关性。采用酶联免疫吸附法检测血浆中铁蛋白、转铁蛋白、铁调素、C反应蛋白和甘油醛-3-磷酸脱氢酶(glyceraldehyde-3-phosphate dehydrogenase,GAPDH)的变化。采用EDock生物信息学工具构建IAA分子与大鼠GAPDH分子的对接模型。结果与对照组相比,IAA高剂量染毒对大鼠白细胞系统有明显抑制效应,总白细胞数目降低51.12%,且中性粒细胞对IAA尤为敏感,数目降低了73.66%(P<0.01),IAA高剂量染毒使大鼠红细胞呈小细胞低色素效应,血红蛋白和红细胞压积分别降低8.60%和8.70%(P<0.05)。但IAA对大鼠血小板系统无明显影响。IAA染毒显著降低大鼠血浆铁、磷、锌和钾含量,显著升高氯、钠和镁含量,而对钙含量无显著影响。与对照组相比,高剂量IAA染毒组铁含量降低67.09%,镁含量上升131.82%(P<0.01)。相关性分析发现IAA染毒后大鼠血浆铁含量与白细胞系统、红细胞系统和血小板系统参数水平总体相关性最强且呈正相关,与白细胞数目、平均红细胞血红蛋白含量和平均红细胞体积相关系数分别为0.637、0.410和0.365(P<0.05)。与对照组相比,IAA高剂量染毒组大鼠血浆C反应蛋白含量显著升高13.30%(P<0.05)。IAA中、高剂量染毒组转铁蛋白和铁调素含量分别显著升高12.73%和11.02%(P<0.05)。而各组血浆铁蛋白和GAPDH水平差异无统计学意义。IAA与大鼠GAPDH对接模型显示IAA可结合酶活性中心第150位半胱氨酸。结论IAA对大鼠白细胞系统具有毒性效应,可引起炎症伴铁缺乏症,使红细OBJECTIVE To clarify the effect of iodoacetic acid(IAA) on the blood system and electrolyte balance,hence further study the intrinsic relation of blood routine parameters and electrolyte levels,major hematological toxicity effects and their pattern after IAA treatment.METHODS Forty-eight 21-day-old male SPF grade Sprague-Dawley(SD) rats were gavaged with 0,6.25,12.5 and 25 mg/kg IAA for 31 days.After detections of blood routine and plasma inorganic ion levels,Spearman correlation coefficients were performed to evaluate their relationship.Changes in ferritin,transferrin,hepcidin,C-reactive protein and glyceraldehyde-3-phosphate dehydrogenase(GAPDH) were assessed by enzyme-linked immunosorbent assays.The EDock bioinformatics tool was applied to docking model of IAA and GAPDH.RESULTS Compared to the control,high-dose IAA exposure had obvious inhibition effect on rat leukocytes with the total number declined by 51.12%,and neutrophils were particularly sensitive to IAA with the number reduced by 73.66%(P<0.01),and rat erythrocytes exhibited a small cell low pigment effect with hemoglobin and hematocrit decreased by 8.60% and 8.70%,respectively(P<0.05).But IAA had little effects on the platelet.Plasma iron,phosphorus,zinc and potassium levels were repressed significantly,while chlorine,sodium and magnesium levels were elevated obviously through IAA exposure.However,plasma calcium levels were hardly affected by IAA.In comparison with the control,iron levels declined by 67.09%,whereas magnesium levels increased by 131.82% in the high-dose group(P<0.01).Overall,correlation analyses uncovered that plasma iron metabolism was most strongly and positively correlated with levels of leukocyte,erythrocyte and platelet system parameters after IAA exposure,and the correlation coefficients of leukocyte number,mean hemoglobin content and mean erythrocyte volume were 0.637,0.410 and 0.365,respectively(P<0.05).Compared to the control,in the high-dose IAA group,the plasma content of C-reactive protein was significantly upregulated by 1

关 键 词：消毒副产物 碘乙酸 血液毒性 铁代谢 电解质平衡 

分 类 号：R12[医药卫生—环境卫生学] R114[医药卫生—公共卫生与预防医学]