慢性砷染毒对大鼠周围神经机械痛觉的影响及甲钴胺的干预作用  

Effect of chronic arsenic exposure on peripheral nerve mechanical algesthesia in rats and potential protection of mecobalamin

作　　者：赖燕 何麒灿 段燕英 LAI Yan;HE Qi-can;DUAN Yan-ying(Poisoning Medicine Department,Hunan Provincial Institute for Occupational Health,Changsha,Hunan 410007,China;Department of Occupational and Environmental Health,Xiangya School of Public Health,Central South University,Changsha,Hunan 410000,China)

机构地区：[1]湖南省职业病防治院中毒医学科,湖南长沙410007 [2]中南大学湘雅公共卫生学院劳动卫生与环境卫生学系,湖南长沙410000

出　　处：《环境与职业医学》2020年第3期260-266,共7页Journal of Environmental and Occupational Medicine

基　　金：湖南省医药卫生科研计划(B2011-110);2018年度研究生创新项目(2018zzts852)。

摘　　要：[背景]砷是广泛存在于自然界的一种有毒类金属元素,经饮水摄入是其威胁人类健康的主要途径。慢性砷暴露造成多器官系统的损伤,周围神经病变引起的感觉异常是最常见症状之一。[目的]探究慢性砷染毒对大鼠周围神经机械痛觉的影响及甲钴胺的干预作用。[方法]28只SPF级SD雄性大鼠随机分为对照组、25 mg·L^-1亚砷酸钠染毒组、100 mg·L^-1亚砷酸钠染毒组、100 mg·L^-1亚砷酸钠染毒+1 mg·kg-1甲钴胺干预组(简称为干预组),经饮水方式进行砷染毒。干预组在100 mg·L^-1亚砷酸钠溶液染毒的同时给予1 mg·kg-1·d-1甲钴胺溶液灌胃处理,连续进行32周。在第10、20、30周时采用Von frey纤维丝测量大鼠后足机械痛阈值,染毒结束时收取24 h尿样及坐骨神经。采用Western blotting法检测神经纤维髓鞘碱性蛋白(MBP)的表达,免疫组化法检测炎症因子γ-干扰素(IFN-γ)、肿瘤坏死因子α(TNF-α)的表达,液相色谱-原子荧光联用法检测尿中砷代谢物浓度。[结果]染毒第20周时,相比于对照组(14.67 g),两个染毒组的机械痛阈值均值(9.14、6.80 g)分别下降了38%、54%(P<0.05),干预组痛阈值(8.60 g)比100 mg·L^-1染毒组上升了27%,但差异无统计学意义。两个染毒组坐骨神经中MBP表达水平(1.93±0.40、2.07±0.20)高于对照组(1.00±0.20)(P<0.05),100 mg·L^-1染毒组炎症因子IFN-γ(14287.98±10218.73)、TNF-α(54.87±7.86)的表达均高于对照组(分别为5704.22±1341.28、37.28±10.12)(P<0.05)。相比于100 mg·L^-1染毒组,干预组MBP表达(1.08±0.32)降低(P<0.05),炎症因子IFN-γ(9408.49±3228.92)、TNF-α(41.64±7.68)的表达无明显变化。染毒组尿中无机砷的质量浓度随染毒质量浓度的增高而增高(P<0.05),干预组[(704.42±207.88)μg·L^-1]比100 mg·L^-1染毒组[(479.04±92.91)μg·L^-1]更高(P<0.05);尿中二甲基砷也随染毒浓度的增高而增高(P<0.05)。[结论]饮水慢性砷染毒引起大鼠机械痛阈值降�[Background] Arsenic is a toxic metalloid element widely distributed in natural environment, and a primary pathway for arsenic exposure is via drinking water. Chronic arsenic exposure may cause damage to multiple organs and systems, and sensory deficits caused by peripheral neuropathies are one of the most common complications. [Objective] This experiment aims to explore the effect of chronic arsenic exposure on peripheral nerve mechanical algesthesia in rats and the potential protection of mecobalamin.[Methods] A total of 28 SPF SD rats were randomly divided into four groups: control group, 25 mg·L^-1 NaAsO2 group, 100 mg·L^-1 NaAsO2 group, and intervention group(100 mg·L^-1 NaAsO2+ 1 mg·kg-1 mecobalamin). The rats were exposed to arsenic by free drinking, and the rats in the intervention group was additionally given 1 mg·kg-1·d-1 mecobalamin solution by gavage;the experiment lasted for 32 weeks. The hind foot mechanical pain threshold was measured at the 10 th, 20 th, and 30 th weeks with Von frey filament, and the 24 h urine samples and sciatic nerve samples were collected at the end of the exposure. The expression of myelin basic protein(MBP) was detected by Western blotting, the expressions of interferon-γ(IFN-γ) and tumor necrosis factor-α(TNF-α) were detected by immunohistochemistry, and the concentrations of arsenic metabolites in urine were detected by liquid chromatography-atomic fluorescence spectrometry.[Results] At the 20 th week, compared with the control group(14.67 g), the mean mechanical pain thresholds of the 25 mg·L^-1 NaAsO2 group(9.14 g) and the 100 mg·L^-1 NaAsO2 group(6.80 g) decreased by 38% and 54% respectively(P < 0.05), and the threshold of the intervention group(8.60 g) was higher than that of the 100 mg·L^-1 NaAsO2 group by 27% without statistical difference. The expression levels of MBP in the 25 mg·L^-1 NaAsO2 group(1.93±0.40) and the 100 mg·L^-1 NaAsO2 group(2.07±0.20) were higher than that in the control group(1.00±0.20)(P < 0.05), and the expressions levels of I

关 键 词：慢性砷染毒 机械痛阈值 甲钴胺 髓鞘碱性蛋白 γ-干扰素 肿瘤坏死因子α 砷代谢 

分 类 号：R114[医药卫生—卫生毒理学]