Effects Of Chronic Exposure To NP At Environmental Concentration On Thyroid Function And Thyroid Hyperplasia Disease In Male Rats And The Interventional Effects Of Zinc Selenium Tea

Objective:1)To examine whether chronic exposure to NP at environmental concentration would induce the imbalance of thyroid hormone level and thyroid dysfunction,and explore the alterations in the expressions of estrogen receptor and thyroxine receptor in NP-induced thyroid hyperplasia disease.2)To examine the protective effect of zinc selenium tea on thyroid function in NP-induced thyroid hyperplasia disease,and explore the protective mechanism of zinc selenium tea on NP-induced thyroid disease.Methods:A total of 240 male SD rats were divided into 7 groups?control group,0.4mg/kg/d?low dose group?,4mg/kg/d?middle dose group?,40mg/kg/d NP group?high dose group?,30?g/kg/d E₂ group?,general tea treatment group,zinc selenium tea treatment group.NP was orally administrated at the dose of 5 ml/kg/day to the rats based on their body mass from 1^stt week to the 34^thh week,the tea group accepted intervention from the 18^thh week.The thyroids of rats were examined by ultrasound on 17^thh week and 34^thh week,respectively;and thyroids tissue and blood samples were collected to detect the FT3,FT4,TSH levels by ELISA,and NP concentration by HPLC.The ultrastructure of left lobe of thyroid was observed by transmission electron microscopy,and pathological change was observed by hematoxylin-eosin staining.ER?,ER?,TR?and TR?IOD/Area in thyroid were measured by immunohistochemistry?IHC?.Expressions of ER?,ER?,TR?,TR?and HMGB1proteins in thyroid were detected by Western Blot.Results:1)on 17^thh week,the FT3 level in the high NP group was significantly higher than that in the control group?P<0.05?.In the high NP group,there were hypoechoic areas,swollen mitochondria,rough endoplasmic reticulum expansion,Irregular nucleus were observed in thyrocyte.NP concentrations in serum and thyroid tissue in the NP treatment groups were significantly higher than those in the control group in dose-response manner(P_thyroid<0.01,P_serum<0.01).The thickness of thyroid follicular epithelium in the NP treatment groups and E₂ group were higher than that in the control group?P<0.01?.And the size of thyroid follicles in NP exposure groupswas lower than that in the control group?P<0.01?.The IOD/Area of ER?,ER?,TR?and TR?increased in the NP exposure group(P_ER?<0.01,P_ER?<0.01,P_TR?<0.01,P_TR?<0.01).The expressions of ER?,TR?and HMGB1 proteins were significantly higher than in the control group(P_ER?<0.01,P_TR?=0.05,P_HMGB1<0.05).And the expression levels of ER??r=0.66,P<0.01?,ER??r=0.57,P<0.01?,TR??r=0.55,P<0.05?,and HMGB1?r=0.80,P<0.01?protein were positively correlated with NP concentration in the thyroid tissue of rats.2)on 34^thh week,compared with the control group,FT3 level in the high NP group increased significantly?P<0.05?,conversely,FT4 level decreased?P<0.05?.In both middle dose and high dose groups,there were hypoechoic areas and nodules in thyroid,moreover,swollen mitochondria,rough endoplasmic reticulum expansion and vesiculation,and deformed nucleus were observed in thyrocyte.NP concentrations in serum and thyroid tissue in the NP treatment groups were significantly higher than those in the control group,in dose-response manner(P_thyroid<0.01,P_serum<0.05).Exposure caused a dose-related increase in NP level in the thyroid and serum of rats.The thickness of thyroid follicular epithelium in the NP treatment groups and E₂group were higher than that in the control group?P<0.01?.The size of thyroid follicles in NP exposure groupswas lower than that in the control group?P<0.01?.The IOD/Area of ER?,ER?,TR?and TR?increased in the NP exposure group(P_ER?<0.01,P_ER?<0.01,P_TR?<0.01,P_TR?<0.01).The expressions of ER?,ER?,TR?,TR?and HMGB1 proteins were significantly higher than in the control group(P_ER?<0.01,P_ER?<0.01,P_TR?<0.01,P_TR?<0.05,P_HMGB1<0.01).In addition,the expression levels of ER??r=0.57,P<0.01?,ER??r=0.73,P<0.01?,TR??r=0.64,P<0.01?,TR??r=0.58,P<0.01?and HMGB1?r=0.74,P<0.01?protein were positively correlated with NP concentration in the thyroid tissue of rats.3)The concentrations of NP in serum and thyroid tissue on 34^thh week were higher than those on 17^thh week,The thickness of the thyroid follicular epithelium increased obviously on 34^thh week.The expressions levels of ER?,ER?,TR?,TR?and HMGB1proteins in the thyroid of rats on 34^thh week were significantly higher than those on 17^thh week?P<0.05?.4)There was no hypoechoic areas in the tea treatment group.Compared with the high NP group,the thickness of thyroid follicular epithelium in thyroid of rats reduced?P<0.01?.The IOD/Area of ER?(P_ER?<0.01),ER?(P_ER?<0.01)and TR?(P_TR?<0.01)in the zinc selenium tea group were lower than those of the high NP groupConclusion:1)Chronic NP exposure could accumulate in thyroid tissue and serum of rats,which might lead to the pathological damage of thyroid tissue,immbalance of thyroid hormone,and thyroid hyperplasia disease as well as changes in the expression of hormone receptor proteins,which might be the involved in the mechanism of NP-induced thyroid dysfunction.2)Zinc selenium tea could decrease the expression levels of ER?,ER?,TR?and TR?proteins in the thyroid tissue of rats exposed to NP,and provide the protective effects for the thyroid damage caused by NP.