摘要
目的研究邻苯二甲酸二乙基己酯(DEHP)和双酚A(BPA)混合染毒对大鼠睾丸损伤作用及与氧化应激关系。方法将32只4周龄SD大鼠随机分为750 mg/kg·bw DEHP、100 mg/kg·bw BPA、750 mg/kg·bw DEHP+100 mg/kg·bw BPA和溶剂对照组,每组8只;用玉米油配制成相应浓度,以5 ml/kg·bw容积连续灌胃染毒6周,1次/d。观察大鼠睾丸脏器系数和组织病理改变、精子数目、血清睾酮(T)和雌二醇(E2)含量,检测睾丸组织丙二醛(MDA)、过氧化氢(H2O2)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)水平,以及氧化应激相关因子SOD、GSH-Px、核因子E2相关因子2(Nrf2)、血红素加氧合酶(HO-1)、γ-谷氨酸半胱氨酸合成酶(Gclc)和硫氧还蛋白还原酶(Txnrd)的基因表达。结果DEHP组及混合剂量组睾丸脏器系数及3个剂量组精子数目明显低于对照组(P<0.05),光学显微镜下可见曲细精管萎缩、生殖细胞大部分消失;混合剂量组血清T水平显著低于对照组(P<0.05);混合剂量组MDA含量升高、SOD活性下降,DEHP组MDA含量和GSH-Px活性均升高,BPA组SOD活性降低,差异均具有统计学意义(P<0.05);混合染毒组的SOD1基因表达降低、SOD3和GSH-Px升高,差异具有统计学意义(P<0.05);混合染毒组Gclc、Txnrd和Nrf2表达低于对照组,DEHP组Txnrd表达也降低,而BPA组Txnrd、Nrf2表达均升高,差异均有统计学意义(P<0.05)。结论DEHP和BPA单独及混合染毒均能导致大鼠睾丸发育不良,生精细胞减少,精子总数下降;可诱导睾丸产生氧化应激,破坏体内抗氧化稳态失衡;DEHP和BPA混合染毒可导致更严重损害。
Objective To study the effect of diethylhexyl phthalate(DEHP)and Bisphenol A(BPA)mixed exposure on testicular injury and its relationship with oxidative stress in rats.Methods Thirty-two 4-weeks-old Sprague Dawley rats were randomly divided into control group DEHP group,BPA group,and combined exposure groups,with 8 rats in each group.DEHP group was treated with 750 mg/kg·bw DEHP,BPA group with 100 mg/kg·bw BPA,and mixed exposure group with 750 mg/kg·bw DEHP and 100 mg/kg·bw BPA.Four groups were exposed adopting administrated by gavage the volume of 5 ml/kg·bw consecutively for 6 weeks,1 times daily.The weight coefficients of testis,sperm count,serum testosterone(T)and Estradiol(E2)levels and testicular tissue pathology and lipid peroxidation were measured.Such as malondialdehyde(MDA),hydrogen peroxide(H2 O2),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and the mRNA expression of oxidative stress related genes:SOD,GSH-Px,Nrf2,HO-1,Gclc and Txnrd.Results The weight coefficient of testis in the DEHP group and the mixed group and the number of sperm in three dose groups were significantly lower than those in the control group(P〈0.05),the atrophy of seminiferous tubules and the disappearance of most of the reproductive cells were observed under the microscope;the level of T in the mixed group was significantly lower than that in the control group(P〈0.05);the content of MDA increased and the activity of SOD decreased in the mixed group,and the content of MDA and the activity of GSH-Px in the DEHP group increased,and the activity of SOD in the BPA group decreased,and the above-metioned difference was statistically significant(P〈0.05);The expression of SOD1 gene in the mixed group was significantly lower than that in the control group,the gene expression of SOD3 and GSH-Px were significantly higher than that in the control group,the difference was statistically significant(P〈0.05);the expression of Gclc,Txnrd and Nrf2 in the mixed group was lower than that in the control group,and the expression of Txnrd in the DEHP group decreased,while the expression of Txnrd and Nrf2 in the BPA group increased,and the differences were statistically significant(P〈0.05).Conclusion DEHP and BPA alone and mixed exposure can lead to testicular dysplasia,spermatogenic cells decreased,the total number of sperm decreased;inducing testicular oxidative stress,destruction of the body of antioxidant steady-state imbalance;DEHP and BPA mixed exposure can lead to more serious damage.
作者
王宇
李登辉
于海洋
段晓旭
张玉敏
裴秀丛
段志文
WANG Yu;LI Deng-hui;YU Hai-yang;DUAN Xiao-xu;ZHANG Yu-min;PEI Xiu-cong;DUAN Zhi-wen(Department of Toxicology,School of Public Health,Shenyang Medical College,Shenyang Liaoning 110034,China)
出处
《毒理学杂志》
CAS
CSCD
2018年第1期29-34,共6页
Journal of Toxicology
基金
辽宁省自然科学基金(201602720)
