腹腔注射多氯联苯118的雄性大鼠甲状腺功能变化观察及其机制探讨  

Effect of intraperitoneal injection of PCB118 on thyroid function in male rats and its mechanism

作　　者：朱晓霞 许文立 段宇[1] ZHU Xiaoxia;XU Wenli;DUAN Yu(Department of Endocrinology,The First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China)

机构地区：[1]南京医科大学第一附属医院内分泌科,南京210029

出　　处：《山东医药》2022年第18期49-54,共6页Shandong Medical Journal

摘　　要：目的观察多氯联苯118(polychlorinated biphenyl 118,PCB118)腹腔注射的雄性大鼠甲状腺功能变化及组织衰老程度,并探讨其可能作用机制。方法24只雄性Wistar大鼠随机分为A、B、C及对照组4组,每组6只。A、B及C组大鼠分别用10、100、1000μg/(kg·d)的PCB118腹腔注射,对照组用等容积玉米油腹腔注射,各组均注射1天/次,一周5次,共注射13周。造模结束时处死各组大鼠,心脏取血,ELISA法检测大鼠血清游离甲状腺素(FT4)、游离三碘甲状腺原氨酸(FT3)及促甲状腺激素(TSH)。取甲状腺组织,采用衰老相关β-半乳糖苷酶(SA-β-gal)染色评估甲状腺组织衰老情况;实时荧光定量PCR法检测各组大鼠甲状腺组织衰老基因(p16、p21、p53)、衰老相关分泌表型(SASP)中的部分因子[白细胞介素-1α(IL-1α)、肿瘤坏死因子α(TNFα)、白细胞介素-6(IL-6)、基质金属肽酶13(MMP13)]mRNA以及线粒体动力学相关蛋白[线粒体自噬调节因子PTEN诱导激酶1(PINK1)、线粒体动力相关蛋白1(DNM1L)、线粒体融合蛋白1(MFN1)、线粒体融合蛋白2(MFN2)]mRNA。结果A、B及C组大鼠血清FT3和FT4水平呈PCB118剂量依赖性降低,TSH水平呈剂量依赖性升高;与对照组比较,B、C组大鼠血清FT3和FT4水平显著下降,TSH水平显著升高(P均<0.05)。与对照组比较,A、B、C组大鼠甲状腺组织SA-β-gal染色阳性率高(P均<0.05);与A、B组比较,C组大鼠甲状腺组织SA-β-gal染色阳性率进一步增高(P均<0.05)。与对照组比较,B、C组大鼠甲状腺组织p16、p21基因相对表达量升高(P均<0.05)。与对照组比较,A、B、C组大鼠甲状腺组织IL-6 mRNA及MMP13 mRNA相对表达量升高,B组大鼠甲状腺组织TNFαmRNA相对表达量升高(P均<0.05);与B组比较,C组大鼠甲状腺组织TNFαmRNA相对表达量下降(P<0.05)。与对照组比较,A组甲状腺组织DNM1L mRNA、MFN1 mRNA相对表达量升高(P均<0.05),B组甲状腺组织PINK1 mRNA、DNM1L mRNA、MFN1 mRNA相对表达量升高(PObjective To observe the secretory function and aging degree in thyroid tissues of rats injected with polychlorinated biphenyl 118(PCB118)intraperitoneally,and to explore the underlying mechanism.Methods Twenty-four male Wistar rats were randomly divided into four groups:groups A,B,C,and control group.Rats of groups A,B,C were intraperitoneally injected with 10,100,and 1000μg/(kg·d)PCB118,respectively;rats in the control group were intraperitoneally injected with corn oil,five days a week,for 13 weeks.At the end of modeling,the rats were euthanized and sacrificed,the blood was collected from the heart.Rats’serum levels of free thyroxine(FT4),free triiodothyronine(FT3)and thyroid-stimulating hormone(TSH)were measured by enzyme-linked immunosorbent assay(ELISA).Thyroid tissues of rats were taken out and their senescence was assessed by aging-relatedβ-galactosidase(SA-β-gal)staining.The qRT-PCR was used to detect mRNA expression levels of senescence genes(p16,p21,p53),senescence-associated secretory phenotype(SASP)factors[interleukin-1α(IL-1α),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and matrix metallopeptidase 13(MMP13)],and mitochondria dynamics regulators[PTEN induced putative kinase 1(PINK1),dynamin1-like(DNML1),mitofusin1(MFN1),and mitofusin2(MFN2)].Results FT3 and FT4 serum concentrations of rats decreased in the groups A,B and C in a PCB118 dose-dependent manner,while TSH increased in a PCB118 dose-dependent manner.Compared with the control group,FT3 and FT4 significantly decreased,and TSH significantly increased in groups B and C(all P<0.05).SA-β-Gal staining positive rate of rats’thyroid tissues was significantly higher in the groups A,B and C than in the control group(all P<0.05);compared with groups A and B,SA-β-Gal staining positive rate increased meaningfully in the group C(P<0.05).Compared with the control group,the mRNA expression levels of p16 and p21 in the rats’thyroid tissues significantly increased in groups B and C(all P<0.05).Compared with the control group,the relativ

关 键 词：多氯联苯118 多氯联苯 甲状腺 甲状腺功能异常 衰老 线粒体 

分 类 号：R58[医药卫生—内分泌]