还原型谷胱甘肽对甲醛和苯诱导的小鼠胚胎发育毒性的影响

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目的研究妊娠期还原型谷胱甘肽(GSH)对经过甲醛和苯联合染毒处理的小鼠胚胎发育的影响。方法将78只孕鼠用不同浓度的甲醛和苯进行吸入染毒,分为对照组(甲醛0 mg/m3、苯0 mg/m3)10只、GSH组(170 mg/kg)8只、低剂量组[甲醛(0.10±0.01)mg/m3、苯(0.11±0.01)mg/m3]10只、低剂量+GSH组[甲醛(0.10±0.01)mg/m3、苯(0.11±0.01)mg/m3、GSH 170 mg/kg]8只、中剂量组[甲醛(5.00±0.30)mg/m3、苯(5.50±0.40)mg/m3]10只、中剂量+GSH组[甲醛(5.00±0.30)mg/m3、苯(5.50±0.40)mg/m3、GSH 170 mg/kg]10只、高剂量组[甲醛(10.00±0.50)mg/m3、苯(11.00±0.50)mg/m3]12只、高剂量+GSH组[甲醛(10.00±0.50)mg/m3、苯(11.00±0.50)mg/m3、GSH 170 mg/kg]10只。记录孕鼠生产情况和存活仔鼠数;称量仔鼠体重,分离肝脏及脑组织,称重后进行RT-PCR,检测发育相关基因的表达情况。结果高剂量组孕鼠的平均产仔数和存活数分别为(10±2)只和(8±4)只,均低于其他各组,差异有统计学意义(P<0.05)。中、高剂量组仔鼠体重低于对照组,差异有统计学意义(P<0.05);而此剂量下注射GSH组的仔鼠体重与对照组差异无统计学意义;未染毒但注射GSH组的仔鼠体重高于对照组,但肝脏、脑的脏器系数低于对照组,且差异有统计学意义(P<0.05)。高剂量组中父系表达基因3(Peg3)、胰岛素样生长因子(IGF-1)表达下降,未染毒但注射GSH组中神经富亮氨酸重复3(LRRN3)表达下调、Peg3表达上调,与对照组比较,差异均有统计学意义(P<0.05)。结论孕鼠注射GSH有利于改善接触甲醛与苯混合气体导致的胚胎异常,但未染毒孕鼠注射该药物对胚胎无益,甚至可能有害。 Objective To study the effect of glutathione (GSH) during pregnancy on mouse embryonic development induced by formaldehyde and benzene. Methods 78 pregnant rats were inhaled with different concentrations of formaldehyde and benzene. The rats were divided into control group (formaldehyde 0 mg / m3, benzene 0 mg / m3) and GSH group (170 mg / kg) Formaldehyde (0.10 ± 0.01) mg / m 3, benzene (0.11 ± 0.01) mg / m 3] and low dose + (5.00 ± 0.30) mg / m 3 and benzene (5.50 ± 0.40) mg / m 3] in middle dose group and middle dose GSH group (5.00 ± 0.30 mg / (10.00 ± 0.50) mg / m 3 and benzene (11.00 ± 0.50) mg / m 3] in high dose group and 12 in benzene (5.50 ± 0.40 mg / m 3 and GSH 170 mg / High dose + GSH group (10.00 ± 0.50 mg / m3 for formaldehyde, 11.00 ± 0.50 mg / m3 for benzene, and 170 mg / kg for GSH). The pregnant rats were sacrificed and the number of surviving pups recorded. The weights of pups were weighed and the liver and brain tissues were isolated. After weighing, RT-PCR was performed to detect the expression of developmental related genes. Results The mean litter size and survival rate of pregnant rats in high dose group were (10 ± 2) and (8 ± 4), respectively, which were lower than those in other groups. The difference was statistically significant (P <0.05). The weight of the offspring of middle and high doses group was lower than that of the control group, the difference was statistically significant (P <0.05); however, there was no significant difference between the weights of the offspring injected GSH group and the control group; The weight of the offspring rats in the group was higher than that in the control group, but the organ coefficients in the liver and brain were lower than those in the control group (P <0.05). The expression of Peg3 and IGF-1 in the high-dose group was decreased, while the expression of LRRN3 was down-regulated and the expression of Peg3 was up-regulated in the untreated GSH group The differences between the two groups were statistically significant (P <0.05). Conclusion Pregnant mice injected with GSH is beneficial to improve embryo abnormalities caused by exposure to formaldehyde and benzene mixed gas, but it is not beneficial to the embryo and may even be harmful to the uninjected pregnant rats injected with this medicine.
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