目的 采用经济合作与发展组织推荐的检测指南407(TG407)法评价五氯酚(PCP)的甲状腺干扰效应.方法 无特定病原体(specific pathogen free,SPF)级SD大鼠30只,按数字表法随机分为对照组、低剂量组(0.33 mg·kg~(-1)·d~(-1) PCP-Na)和高剂量组(30 mg·kg~(-1)·d~(-1) PCP-Na),每组雌雄各5只,每日经口灌胃,连续28 d.染毒结束后,观察PCP-Na对大鼠甲状腺组织学的影响和血清甲状腺激素(THs)水平,包括总三碘甲状腺原氨酸(TT_3)、总四碘甲状腺原氨酸(TT_4)、游离T_3(FT_3)、游离T_4 (FT-4);实时定量PCR法检测肝脏2种甲状腺受体(TRs)和3种脱碘酶(Dios)基因表达水平.结果 30 mg·kg~(-1)·d~(-1)剂量的PCP-Na可导致SD大鼠肝重和肝脏系数增加,雄鼠和雌鼠肝脏系数分别为(4.82±0.42)%和(4.99±0.17)%,较对照组[分别为(3.54±0.14)%、(3.52±0.19)%]增加了36.2%(t=7.338,P<0.01)和41.8%(t=8.955,P<0.01),而肾和甲状腺未见明显影响;高剂量组雄鼠血清TT_4和FT_4浓度分别为(64.95±7.16)nmol/L和(8.16±2.29)pmol/L,与对照组[分别为(88.48±6.99)nmol/L、(14.13±1.68)pmol/L]相比降低了26.6%(t=-3.999,P<0.01)和42.3%(t=-4.112,P<0.01),雌鼠血清FT_4浓度为(4.94±0.89)pmol/L,与对照组[(11.10±3.40)pmol/L]相比降低55.5%(t=-3.380,P=0.012),TT_3和FT_3浓度分别为(1.92±0.24)nmol/L和(3.05±0.79)pmol/L,与对照组[分别为(1.10±0.23)nmol/L、(1.96±0.32)pmol/L]相比分别增加74.5%(t=5.263,P<0.01)和55.6%(t=3.495,P<0.01);高剂量PCP-Na不影响大鼠肝TRα、TRβ、DioⅢ基因表达水平,但Dio Ⅰ和DioⅡ显示了不同性别的敏感性,雄鼠高剂量组Dio Ⅱ表达(0.209±0.017)较对照组(1.006±0.137)下调79.2%(t=-5.426,P<0.01),雌鼠高剂量组Dio Ⅰ表达(1.844±0.189)较对照组(1.005±0.083)上调66.6%(t=4.359,P<0.01);高剂量PCP-Na可导致甲状腺滤泡上皮细胞增生,滤泡壁明显增厚,胶质减少.0.33 mg·kg~(-1)·d~(-1)剂量的PCP-Na未引起血清THs显著性变化,也未影响大鼠肝脏中TRα、TRβ、DioⅠ～Ⅲ基因表达水平,但存在少量散在的淋巴细胞浸润,可见部分滤泡扩大和轻度滤泡壁增厚.结论 PCP具有甲状腺干扰效应.
目的 採用經濟閤作與髮展組織推薦的檢測指南407(TG407)法評價五氯酚(PCP)的甲狀腺榦擾效應.方法 無特定病原體(specific pathogen free,SPF)級SD大鼠30隻,按數字錶法隨機分為對照組、低劑量組(0.33 mg·kg~(-1)·d~(-1) PCP-Na)和高劑量組(30 mg·kg~(-1)·d~(-1) PCP-Na),每組雌雄各5隻,每日經口灌胃,連續28 d.染毒結束後,觀察PCP-Na對大鼠甲狀腺組織學的影響和血清甲狀腺激素(THs)水平,包括總三碘甲狀腺原氨痠(TT_3)、總四碘甲狀腺原氨痠(TT_4)、遊離T_3(FT_3)、遊離T_4 (FT-4);實時定量PCR法檢測肝髒2種甲狀腺受體(TRs)和3種脫碘酶(Dios)基因錶達水平.結果 30 mg·kg~(-1)·d~(-1)劑量的PCP-Na可導緻SD大鼠肝重和肝髒繫數增加,雄鼠和雌鼠肝髒繫數分彆為(4.82±0.42)%和(4.99±0.17)%,較對照組[分彆為(3.54±0.14)%、(3.52±0.19)%]增加瞭36.2%(t=7.338,P<0.01)和41.8%(t=8.955,P<0.01),而腎和甲狀腺未見明顯影響;高劑量組雄鼠血清TT_4和FT_4濃度分彆為(64.95±7.16)nmol/L和(8.16±2.29)pmol/L,與對照組[分彆為(88.48±6.99)nmol/L、(14.13±1.68)pmol/L]相比降低瞭26.6%(t=-3.999,P<0.01)和42.3%(t=-4.112,P<0.01),雌鼠血清FT_4濃度為(4.94±0.89)pmol/L,與對照組[(11.10±3.40)pmol/L]相比降低55.5%(t=-3.380,P=0.012),TT_3和FT_3濃度分彆為(1.92±0.24)nmol/L和(3.05±0.79)pmol/L,與對照組[分彆為(1.10±0.23)nmol/L、(1.96±0.32)pmol/L]相比分彆增加74.5%(t=5.263,P<0.01)和55.6%(t=3.495,P<0.01);高劑量PCP-Na不影響大鼠肝TRα、TRβ、DioⅢ基因錶達水平,但Dio Ⅰ和DioⅡ顯示瞭不同性彆的敏感性,雄鼠高劑量組Dio Ⅱ錶達(0.209±0.017)較對照組(1.006±0.137)下調79.2%(t=-5.426,P<0.01),雌鼠高劑量組Dio Ⅰ錶達(1.844±0.189)較對照組(1.005±0.083)上調66.6%(t=4.359,P<0.01);高劑量PCP-Na可導緻甲狀腺濾泡上皮細胞增生,濾泡壁明顯增厚,膠質減少.0.33 mg·kg~(-1)·d~(-1)劑量的PCP-Na未引起血清THs顯著性變化,也未影響大鼠肝髒中TRα、TRβ、DioⅠ～Ⅲ基因錶達水平,但存在少量散在的淋巴細胞浸潤,可見部分濾泡擴大和輕度濾泡壁增厚.結論 PCP具有甲狀腺榦擾效應.
목적 채용경제합작여발전조직추천적검측지남407(TG407)법평개오록분(PCP)적갑상선간우효응.방법 무특정병원체(specific pathogen free,SPF)급SD대서30지,안수자표법수궤분위대조조、저제량조(0.33 mg·kg~(-1)·d~(-1) PCP-Na)화고제량조(30 mg·kg~(-1)·d~(-1) PCP-Na),매조자웅각5지,매일경구관위,련속28 d.염독결속후,관찰PCP-Na대대서갑상선조직학적영향화혈청갑상선격소(THs)수평,포괄총삼전갑상선원안산(TT_3)、총사전갑상선원안산(TT_4)、유리T_3(FT_3)、유리T_4 (FT-4);실시정량PCR법검측간장2충갑상선수체(TRs)화3충탈전매(Dios)기인표체수평.결과 30 mg·kg~(-1)·d~(-1)제량적PCP-Na가도치SD대서간중화간장계수증가,웅서화자서간장계수분별위(4.82±0.42)%화(4.99±0.17)%,교대조조[분별위(3.54±0.14)%、(3.52±0.19)%]증가료36.2%(t=7.338,P<0.01)화41.8%(t=8.955,P<0.01),이신화갑상선미견명현영향;고제량조웅서혈청TT_4화FT_4농도분별위(64.95±7.16)nmol/L화(8.16±2.29)pmol/L,여대조조[분별위(88.48±6.99)nmol/L、(14.13±1.68)pmol/L]상비강저료26.6%(t=-3.999,P<0.01)화42.3%(t=-4.112,P<0.01),자서혈청FT_4농도위(4.94±0.89)pmol/L,여대조조[(11.10±3.40)pmol/L]상비강저55.5%(t=-3.380,P=0.012),TT_3화FT_3농도분별위(1.92±0.24)nmol/L화(3.05±0.79)pmol/L,여대조조[분별위(1.10±0.23)nmol/L、(1.96±0.32)pmol/L]상비분별증가74.5%(t=5.263,P<0.01)화55.6%(t=3.495,P<0.01);고제량PCP-Na불영향대서간TRα、TRβ、DioⅢ기인표체수평,단Dio Ⅰ화DioⅡ현시료불동성별적민감성,웅서고제량조Dio Ⅱ표체(0.209±0.017)교대조조(1.006±0.137)하조79.2%(t=-5.426,P<0.01),자서고제량조Dio Ⅰ표체(1.844±0.189)교대조조(1.005±0.083)상조66.6%(t=4.359,P<0.01);고제량PCP-Na가도치갑상선려포상피세포증생,려포벽명현증후,효질감소.0.33 mg·kg~(-1)·d~(-1)제량적PCP-Na미인기혈청THs현저성변화,야미영향대서간장중TRα、TRβ、DioⅠ～Ⅲ기인표체수평,단존재소량산재적림파세포침윤,가견부분려포확대화경도려포벽증후.결론 PCP구유갑상선간우효응.
Objective To assess thyroid disruption induced by sodium pentachlorophenol (PCP) using Organization for Economic Co-operation and Development (OECD) recommended TG 407 method. Methods A total of 30 specific pathogen free(SPF) SD adult male and female rats were randomly divided into 3 groups,and treated with water,0. 33 and 30 mg·kg~(-1)·d~(-1) of PCP-Na by oral gavage for consecutive 28 days, respectively. After final treatment, histological changes of thyroid were observed by hematoxylin-eosin stain, and the levels of thyroid hormones (total thyroxine (TT_4), free thyroxine (FT_4),total triiodothyronine (TT_3), and free triiodothyronine (FT_3) were determined by radioimmunoassay. The expression levels of thyroid receptors (TRα and TRβ) mRNA and deiodinases (Dio Ⅰ,Dio Ⅱ and Dio Ⅲ)mRNA in liver were analyzed by RT-PCR. Results In high dose group,liver weight coefficient of male and female rats were (4.82±0. 42)% and (4.99±0.17)% ,increased by 36.2% (t=7.338 ,P<0.01 ) and 41.8%(t = 8.955, P<0.01), compared to control group ((3.54±0. 14)%, (3.52±0.19)%), respectively ,while the significant changes of kidney or thyroid weight were not observed. In high dose group, the levels of TT_4 and FT_4 in serum of male rats were (64.95±7. 16) nmol/L and (8.16±2.29) pmol/L, and decreased by 26.6% (t=-3.999,P<0.01) and 42.3% (t=-4.112,P<0.01) compared to control group((88.48±6.99) nmol/L, (14.13±1.68) pmol/L). In the same group, FT_4 in serum of female rats was (4.94±0.89) pmol/L,decreased by 55.5% (t=-3. 380,P =0.012) compared to control group( (11.10±3.40) pmol/L) and TT_3 and FT_3 in serum of female rats were (1.92±0.24) nmoL/L and (3.05±0.79) pmol/L,increased by 74.5% (t=5.263,P<0.01) and 55.6% (t=3.495,P<0.01) compared to control group( (1.10±0.23) nmol/L, (1.96±0. 32) pmol/L), respectively. PCP-Na didn't affect the expression levels of TRα, TRβ, Dio Ⅲ mRNA in high dose group, while Dio Ⅱ expression of male rats (0.209±0.017) down-regulated by 79.2% (t=-5.426, P <0.01) compared to control group (1.006±0.137), and Dio Ⅰ expression of female rats (1.844±0.189) up-regulated by 66.6% (t=4.359 ,P<0.01) compared to control group (1.005±0.083) ,indicating Dio Ⅰ and Dio Ⅱ poss different sensitivity to adverse effects induced by PCP-Na between male and female rats. The histopathological results showed that PCP-Na could give rise to hyperplasia of the follicular epithelium cells, and the depletion of colloid. There were no significant changes in serum THs levels and expression of TRα, TRβ, Dio Ⅰ-Ⅲ mRNA in low dose group. However, sporadic lymphocytic infiltration, follicles amplification in part and slightly increased in thickness of follicular cells were observed in this group. Conclusion PCP is a kind of thyroid disrupting chemical.
