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目的研究甲醛和二甲苯联合染毒对小鼠神经系统的毒性作用及其机制,为综合评价室内装修材料中甲醛和二甲苯对人体健康的危害提供科学依据。方法选用健康清洁级昆明小鼠72只,按完全随机设计,将小鼠随机分为12组,每组6只,雌雄各半,分别为低剂量(5 mg/kg)、中剂量(10 mg/kg)、高剂量甲醛染毒组(20 mg/kg)和生理盐水对照组,低剂量(50 mg/kg)、中剂量(100 mg/kg)、高剂量二甲苯染毒组(150 mg/kg)和花生油对照组以及低剂量(2.5 mg/kg甲醛+25 mg/kg二甲苯)、中剂量(5 mg/kg甲醛+50 mg/kg二甲苯)、高剂量联合染毒组(10 mg/kg甲醛+75 mg/kg二甲苯)以及生理盐水+花生油(体积比1∶1)对照组;采用腹腔注射染毒,连续7 d。染毒结束后,采用Morris水迷宫实验和流式细胞凋亡对小鼠进行神经毒性的研究。结果与相应对照组相比,中、高剂量甲醛、二甲苯以及联合染毒组小鼠逃避潜伏期延长,差异均有统计学意义(P<0.05);与相同剂量联合染毒组比较,中、高剂量甲醛、二甲苯联合染毒组雌性小鼠逃避潜伏期缩短,差异均有统计学意义(P<0.05);随着染毒时间的延长,各染毒组小鼠总体逃避潜伏期呈缩短趋势。在空间探索实验中,与相应对照组相比,中、高剂量甲醛、二甲苯染毒组以及各剂量联合染毒组小鼠找到平台的时间延长,在原平台象限游泳时间缩短,原平台象限游泳距离占总距离百分比下降,差异均有统计学意义(P<0.05);与相同剂量联合染毒组比较,各剂量甲醛染毒组和中、高剂量二甲苯染毒组小鼠找到平台的时间缩短,高剂量甲醛染毒组和二甲苯染毒组雌性小鼠、雄性小鼠以及小鼠总体在原平台象限游泳时间延长,原平台象限游泳距离占总距离百分比上升,差异有统计学意义(P<0.05)。与相应对照组相比,各剂量甲醛、二甲苯以及联合染毒组小鼠海马细胞早期凋亡率以及高剂量甲醛、二甲苯以及联合染毒组晚期凋亡率均升高,差异均有统计学意义(P<0.05);且随着染毒剂量的升高,小鼠海马细胞早期、晚期凋亡率呈上升趋势。与相同剂量联合染毒组比较,中、高剂量甲醛、二甲苯染毒组小鼠早期凋亡率均下降,高剂量甲醛、二甲苯染毒组雌性小鼠、雄性小鼠和小鼠总体晚期凋亡率均下降,差异均有统计学意义(P<0.05)。结论甲醛和二甲苯联合染毒能降低小鼠的学习记忆能力,对神经系统具有一定毒性作用,且二者联合染毒具有一定的协同作用。
Objective To study the toxic effects of formaldehyde and xylene on the nervous system of mice and to provide a scientific basis for the comprehensive evaluation of the hazards of formaldehyde and xylene to human health in interior decoration materials. Methods Seventy - two healthy Kunming mice were randomly divided into 12 groups (6 mice in each group) randomly divided into two groups: low dose (5 mg / kg) and middle dose (10 mg / kg), high dose formaldehyde exposure group (20 mg / kg) and saline control group, low dose (50 mg / kg), middle dose (100 mg / / kg) and the peanut oil control group and the low dose (2.5 mg / kg formaldehyde +25 mg / kg xylene), the middle dose (5 mg / kg formaldehyde +50 mg / kg xylene) mg / kg formaldehyde + 75 mg / kg xylene) and saline + peanut oil (1: 1 by volume). The rats were injected intraperitoneally for 7 days. After the exposure, mice were subjected to neurotoxicity using the Morris water maze test and flow cytometry. Results Compared with the corresponding control group, the escape latency of middle and high dose of formaldehyde, xylene and combined exposure group was longer than that of the corresponding control group (P <0.05). Compared with the same dose of combined exposure group, The escape latency of female mice exposed to high doses of formaldehyde and xylene was shortened significantly (P <0.05). With the prolongation of exposure time, the overall escape latency of mice in each exposure group was shortened. In the space exploration experiment, compared with the corresponding control group, the medium and high dose formaldehyde and xylene exposure groups and the mice in each dose combined exposure group found the platform prolonged, the swimming time in the original platform quadrant was shortened, the original platform quadrant swimming (P <0.05). Compared with the same dose and combined exposure group, the mice in each dose of formaldehyde exposure group and medium and high dose xylene exposure group found the platform time Shortening, high dose formaldehyde exposure group and xylene exposure group female mice, male mice and mice in the original platform quadrant swimming time extension, the original platform quadrant swimming distance percentage of the total distance increased, the difference was statistically significant (P <0.05). Compared with the corresponding control group, the early apoptotic rate of hippocampal cells and the late apoptotic rates of hippocampal neurons in high-dose, high-dose and high-dose groups of mice exposed to formaldehyde, xylene and combined exposure all increased, with statistical differences (P <0.05). And with the increase of exposure dose, the apoptosis rate of early and late stages of hippocampal cells in mice showed an upward trend. Compared with the same dose of combined exposure group, the early apoptotic rate of mice in middle and high dose of formaldehyde and xylene-treated groups decreased, while in the high dose of formaldehyde and xylene-treated female, male and mouse, Apoptosis rate decreased, the differences were statistically significant (P <0.05). Conclusion The combination of formaldehyde and xylene can reduce the learning and memory ability of mice and has some toxic effects on the nervous system, and the synergistic effects of the combination of the two drugs have certain synergies.