| Objective:The model of mixed arsenic exposure was used in rabbits,and5-Aza-2'-deoxycytidine?5-Aza-DC?and D,L-sulforaphane?SFP?were used to investigate the estrogen effect of arsenic on thyroid function and the toxic mechanism of skin lesion.Methods:the rabbit is divided into 10 groups:blank control group,the low dose of arsenic exposure group(0.075 mg·kg-1·w-1),the medium dose of arsenic exposure group(0.15 mg·kg-1·w-1),the high dose of arsenic exposure group(0.75 mg·kg-1·w-1),5-Aza-DC intervention low-dose arsenic group,5-Aza-DC intervention medium-dose arsenic group,5-Aza-DC intervention high-dose arsenic group,SFP intervention low-dose arsenic group,SFP intervention medium-dose arsenic group,SFP intervention high-dose arsenic group,each group of eight rabbit,male and female half and half.The rabbits were allowed to drink water freely and continued to be infected for 14 weeks.Starting from week 9,the5-aza-DC intervention group was injected with 0.125mg·kg-11 5-aza-DC intravenously,and the SFP intervention group was injected with 1.25mg·kg-1SFP intravenously,twice a week,for 6 consecutive weeks.At the end of the 14th week,blood was collected from each group of rabbits and skin biopsy was performed on the same part of the back to obtain the full thickness of the skin.Serum GSH,MDA,COX-2,E2,TT3,TT4 and TSH were determined by ELISA.mRNA levels of ER?,ER?,PI3K,Nrf2,Keap1,As3MT and N6AMT1 in the skin tissues of rabbits of different genders,as well as mRNA levels of ER?,ER?,PI3K,Nrf2,Keap1,As3MT,N6AMT1,TR?,TR?,PTEN and INPP4B in the blood were detected by RT-PCR.The expression levels of Nrf2 and Keap1 in blood and skin were detected by Western blot.Results:E2 in the blood of female and male rabbits was significantly reduced in the medium and high-dose arsenic groups compared with the control group,with statistically significant differences?all P<0.001?.The expression levels of TT3,TT4 and TSH in female and male blood were all higher than those in the control group in the low,medium and high dose arsenic groups,with statistically significant differences?all P<0.001?.The expression levels of TT3,TT4 and TSH in blood in the5-Aza-DC intervention medium-dose arsenic group and 5-Aza-DC intervention high-dose arsenic group were significantly lower than those in the same dose arsenic group?all P<0.001?.The expression of TT3,TT4 and TSH in the blood of female and male 5-Aza-dc and SFP intervention of medium-dose and high-dose groups were all lower than that of the same dose arsenic group,with statistically significant differences?all P<0.001?.The expression levels of MDA in the low,medium and high dose arsenic groups were higher than those in the control group?all P<0.001?.The expression of 5-Aza-DC interventionin of low-dose,medium-dose and high-dose arsenic groups was significantly lower than that in the same dose arsenic group?all P<0.001?.The expression levels of female GSH in the high-dose arsenic group were lower than those in the control group,while the expression levels of male GSH in the low-dose,medium-dose and high-dose arsenic groups were lower than those in the control group?all P<0.001?.The expression levels of female COX-2 in the medium and high-dose arsenic groups were higher than those in the control group,and the expression levels of females in the high-dose arsenic group were higher than that of males,with statistically significant differences?all P<0.001?.In the blood,mRNA expression of ER?in the female medium-dose and high-dose arsenic group was higher than that in the control group?P=0.026,P=0.004?,and mRNA expression of ER?in the male high-dose arsenic group was higher than that in the control group,the low-dose arsenic group and the high-dose arsenic group,with statistically significant differences?P=0.007,P=0.002,P=0.001?.In the blood,the expressions of TR?and TR?mRNA in the female middle-dose and high-dose arsenic group were higher than those in the control group,the difference was statistically significant?all P<0.05?.In the blood,the expression of Nrf2 protein in the low-dose and high-dose arsenic groups was higher than that in the control group,and the difference was statistically significant?all P<0.05?.The expression of As3MT mRNA in the female high-dose arsenic group was higher than that in the control group and the low-dose arsenic group?P=0.035,P=0.033?.The expression of N6AMT1 mRNA in the male high-dose arsenic group was higher than that in the low-dose arsenic group?P=0.049?.The expression of PTEN mRNA in the blood in the male low-dose arsenic group was higher than that in the control group and the female low-dose arsenic group,and the difference was statistically significant?P=0.044,P=0.001?.The expression of ER?mRNA in the low-dose and high-dose arsenic groups in the skin was significantly lower than that in the control group?P=0.001,P=0.031?.The expression of PI3K mRNA in the low and medium dose arsenic group in skin of female was significantly higher than that in the control group?all P<0.05?.Conclusion:Arsenic exposure can exert estrogen effect,restrain rabbit blood endogenous estrogen E2,promote the blood TT3,TT4,TSH,ER?mRNA and medium and high dose of arsenic group in the female rabbit TR?and TR?mRNA expression and change of male and female rabbit skin estrogen receptor expression,and in combination with oxidative stress approach,thus mutual induction of thyroid dysfunction and play a role in skin lesion. |
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