硒对轻度缺碘大鼠组织硒含量及谷胱甘肽过氧化物酶活力影响的动态观察

轻度缺碘时缺硒或补硒可明显降低或增加大鼠组织硒含量和谷胱甘肽过氧化物酶（ＧＰｘ）活力，但随时间的延长各组织变化趋势不同。在４周内肝脏和肾硒含量和ＧＰｘ活力变化幅度大，在８周时红细胞的硒含量和ＧＰｘ活力仍有继续增加或降低的趋势。大脑和甲状腺硒含量和ＧＰｘ活力缺硒后反而升高，但增加幅度明显低于补硒后的增加幅度。提示大脑可优先得到硒，大脑和甲状腺具有较强的维持抗氧化状态的能力。肝脏、肾脏和红细胞可能分别是硒缺乏早期和后期重要器官硒的主要来源。红细胞可能起“硒储备库”的作用。     

硒对大鼠高碘性Ⅰ型脱碘酶损伤的干预作用

目的研究高碘性甲状腺损伤的机制并寻求合适的硒干预剂量.方法 50只Wistar大鼠分为5组正常组、高碘组(饮水含碘酸钾48 mg/L)和3个补硒组(饮水含碘酸钾48 mg/L,亚硒酸钠分别为0.5、1.0、2.0 mg/L),共喂养36周.放射免疫法测定甲状腺激素水平,测定肝脏和肾脏组织Ⅰ型脱碘酶(IDI)活性,以RT-PCR测定IDI mRNA水平.结果与正常组比较,高碘组肝、肾IDI活性[(17.1±2.1,2.67±1.10)pmol I·mg-1·min-1vs(13.0±2.9,1.52±0.44)pmol I·mg-1·min-1]、mRNA水平(1.78±0.14,1.55±0.17vs0.90±0.05,0.58±0.12,均P＜0.05)下降(均P＜0.05),而补充0.5mg/L硒组上述指标与正常组差异无统计学意义.结论 IDI活力、mRNA水平下降可能是高碘性甲状腺损伤的机制之一,而补充硒应选择合适的干预剂量.     

硒对大鼠高碘性I型脱碘酶损伤的干预作用

目的研究高碘性甲状腺损伤的机制并寻求合适的硒干预剂量。方法50只Wistar大鼠分为5组正常组、高碘组(饮水含碘酸钾48mg/L)和3个补硒组(饮水含碘酸钾48mg/L,亚硒酸钠分别为0.5、1.0、2.0mg/L),共喂养36周。放射免疫法测定甲状腺激素水平,测定肝脏和肾脏组织Ⅰ型脱碘酶(IDI)活性,以RT-PCR测定IDImRNA水平。结果与正常组比较,高碘组肝、肾IDI活性[(17.1±2.1,2.67±1.10)pmolI·mg-1·min-1vs(13.0±2.9,1.52±0.44)pmolI·mg-1·min-1]、mRNA水平(1.78±0.14,1.55±0.17vs0.90±0.05,0.58±0.12,均P<0.05)下降(均P<0.05),而补充0.5mg/L硒组上述指标与正常组差异无统计学意义。结论IDI活力、mRNA水平下降可能是高碘性甲状腺损伤的机制之一,而补充硒应选择合适的干预剂量。     

硒对轻度缺碘大鼠组织硒含量及谷胱甘肽过氧化物酶活力影…

轻度缺碘时缺硒或补硒可明显降低或增加大鼠组织含量和谷胱甘肽过氧化物酶（ＧＰｘ）活力，但随时间的延长各组织变化趋势不同。在４周内肝脏和肾硒含量和ＧＰｘ活力变化幅度大，在８周时红细胞的硒含量和ＧＰｘ活力仍有继续增加或降低的趋势。大脑和甲状腺硒含量和ＧＰｘ活力缺硒后反而升高，但增加幅度明显低于补硒后的增加幅度，提示大脑可优先得到硒，大脑和甲状腺具有较强的维持抗氧化状态的能力。肝脏、肾脏和红细胞可能分别是     

碘硒缺乏对大鼠肝、脑T_45′—脱碘酶活性影响

本文应用2×2析因实验设计将wistar大鼠分为四组:I~+Se~+,I~+Se~-,I~-Se~+及1~-Se~-。测定了喂养30周大鼠肝脏、大脑组织T_45'—脱碘酶活性以及血清T_4、T_3及rT_3水平。结果表明大鼠肝脏T_45'—脱碘酶活性于低硒组(I~+Se~-和I~-Se~-)明显低于补硒组(I~+Se~+和1~-Se~+),而碘因素对此无影啊;脑组织T_45'—脱碘酶活性在四组中无明显差别。血清T_4、rT_3水平于低碘组明显低于补碘组,T_3变化不明显;而低硒可升高血清T_4水平,并有升高rT_3趋势,碘硒交互作用明显,主要表现补碘低硒(I~+Se~-)可明显升高T_4、rT_3水平,而低碘补硒(I~-Se~+)作用则相反。上述结果提示低硒时肝脏T_45'—脱碘酶活性下降可能是血清T_4、rT_3升高的直接原因,在本实验中碘硒两因素对血清T_3无明显作用。     

硒对鸡胚脑发育的影响

目的观察补硒对正常鸡胚脑谷胱甘肽过氧化物酶(GPx)、Ⅱ型脱碘酶(IDⅡ)活性和生长相关蛋白(GAP-43)表达的影响,探讨硒对正常动物脑发育的作用。方法对孵育8 d的鸡胚分别注射不同剂量的MSeC(含0、1、5、10、20、40 μg硒),孵育至第20天时处死。测定脑组织中硒、GPx活性、IDⅡ活性,检测GAP-43蛋白的表达。结果对正常鸡胚补硒,可提高脑硒水平、脑GPx活性及GAP-43的表达,补硒量与脑硒、脑GPx活性显著相关(P< 0.01),而与脑IDⅡ活性无相关性。结论MSeC可有效提高鸡胚脑组织硒水平、脑GPx活性和GAP-43的表达,对脑IDⅡ活性没有影响。对正常鸡胚适量补硒可能会促进神经系统的生长和发育。     

硒与甲状腺疾病

硒是人体所必需的一种微量元素,在机体中发挥多种生物学作用,如抗氧化、提高免疫功能、抗肿瘤等。硒和碘一样,参与甲状腺激素的合成、活化及代谢过程,从而影响甲状腺功能。在甲状腺肿、自身免疫性甲状腺疾病、甲状腺癌等患者中,血清硒的水平都存在异常。后者可能通过影响甲状腺滤泡上皮细胞内多种含硒基蛋白酶和(或)影响机体的免疫功能而导致甲状腺疾病的发生与发展。给与某些甲状腺疾病患者含硒制剂可以改善甲状腺功能,这为甲状腺疾病的治疗另辟蹊径。     

Effect of selenium supplementation on thyroid hormone metabolism in an iodine and selenium deficient population

OBJECTIVE Severe selenlum deficiency has been documented In northern Zaïre, already known as one of the most Iodine deficient regions In the world and characterized by a predominance of the myxoedematous form of cretinism. This has been attributed to the double deficiency of essential trace elements. A short selenium supplementation programme was conducted In this area to evaluate the effects of a selenium supplementation on thyroid diseases. DESIGN Placebo or selenium 50 ?g as selenomethionine was administered once dally for 2 months. Blood and urine samples were collected before and after supplementation. PATIENTS Fifty-two healthy schoolchildren from northern Zaire. MEASUREMENT Selenium status, thyroid function and urinary Iodide were determined. RESULTS After 2 months of selenium supplementation, mean±SD serum T4 decreased from 73.1 ± 45.4 to 48.3 ± 23.7 nmol/l (P <0.001), serum FT4 from 11.8.6.7 to 8.4.41 pmol/l (P, 0.01), and serum rT3 from 124.115 to 90.72 pmol/l (P < 0.05), without significant change In serum T3 and serum TSH. CONCLUSION Delodinase type I which has been shown to be a seleno-enzyme could account for the changes in thyroid hormones In our subjects. Our data show that selenium plays a definite role in thyroid hormone metabolism In humans. Selenium could be an Important cofactor in the clinical picture of Iodine deficiency In Central Africa could be Involved In the aetiology of both forms of cretinism.     

缺碘大鼠补碘对脑内甲状腺激素受体的影响

目的研究缺碘大鼠补充不同质量浓度碘后脑内甲状腺激素受体与激素结合动力学参数的变化。方法复制Wistar低碘大鼠,然后根据饮用不同质量浓度的碘水来分组。选用第2代20日龄仔鼠实验,测定甲状腺功能状态,利用放射配体结合分析法测定脑内T3受体。结果①血清T3浓度:低碘组(LI)、高碘组(HI)、适碘组(AI)与正常对照组(N)相比,差异无显著意义(P> 0.05)。血清FT3:LI组、HI组明显高于N组(P< 0.05);②血清T4和FT4:LI组和HI组均显著低于N组(P< 0.05);③受体最大结合容量(MBC):LI组明显高于N组(P< 0.05)。结论LI组血中TT4和FT4低于N组,而脑中T3核受体MBC高于N组,提示甲状腺功能低下(甲低)状态下,脑组织中T3核受体有代偿性升高。高碘状态下缺碘大鼠脑细胞核T3核受体、MBC虽略有升高,但血中TT4和FT4却低于正常,提示长期缺碘后过量补碘会出现碘性甲低。长期缺碘后,即使补充适量碘也会出现一过性碘性甲状腺功能亢进(甲亢)。     

碘和硒对低碘鼠甲状腺重量及血清激素的影响

目的　研究硒、碘及两者联用对低碘大鼠甲状腺大小、血清甲状腺激素及促甲状腺激素释放激素(TRH)的影响。方法　给第 2代低碘鼠投于不同浓度的硒和碘 ,7周后 ,分别取甲状腺称重 ,并用放射免疫法测定血清中 T3、T4、FT3、FT4、TRH浓度及下丘脑 TRH含量。结果　与低碘组相比 ,补碘后甲状腺重量减轻 ,血中FT4、T4水平明显升高 ,血中 TRH浓度下降 ,下丘脑 TRH含量升高 ,补硒对甲状腺重量及血清 FT4、T4浓度也有一定的影响。结论　碘、硒及两者联用对低碘鼠甲状腺重量、血清 T4、FT4、TRH及下丘脑 TRH浓度的改变有重要作用     

碘硒缺乏对大鼠甲状腺细胞膜通透性影响——碘硒对甲状腺影响研究之Ⅲ

应用2×2析因实验设计将 Wistar 大鼠随机分为四组:I~+Se~+组,I~+Se~-组,I~-Se~+组。I~-Se~-组。采用辣根过氧化物酶(HRP)示踪技术观察了喂养30周大鼠甲状腺细胞膜通透性变化。结果表明,缺碘组(I~-Se~+和 I~-Se~-)含 HRP 反应产物细胞的数密度明显高于补碘组(I~+Se~+和 I~+Se~-),缺硒也有此作用,但其作用效果远不如缺碘的作用显著,而主要表观在缺碘的条件下,缺硒可使含反应产物细胞数量明显增多,但在碘正常情况下缺硒的影响则不明显。提示缺碘是造成甲状腺细胞损伤而膜通透性增大的主要原因,在缺碘条件下缺硒可加重细胞损伤。     

低碘和高碘对大鼠甲状腺细胞凋亡的影响

目的 研究低碘和高碘对大鼠甲状腺细胞凋亡的影响。方法 利用病区的低碘粮食喂养大鼠，同时饮用不同质量浓度的加碘水，复制低碘和高碘动物模型，于20周后在光、电镜下观察甲状腺形态结构改变，原位末端标记方法对甲状腺细胞凋亡进行检测。结果 与对照组相比，低碘和高碘组甲状腺凋亡细胞数明显增多。结论 低碘和高碘均诱发大鼠甲状腺细胞凋亡，进而调节甲状腺的形态结构和功能。其中以低碘组作用明显，提示细胞凋亡过度是引起低碘和高碘性甲状腺功能低下的重要原因。     

碘硒联合缺乏对大鼠甲状腺重量血清激素及酶活性的影响

应用２×２析因实验设计将Ｗｉｓｔａｒ大鼠随机分为四组：Ｉ＋Ｓｅ＋、Ｉ＋Ｓｅ－、Ｉ－Ｓｅ＋、Ｉ－Ｓｅ－。观察了喂养１２周和３２周大鼠甲状腺重量，血清总Ｔ４、Ｔ３水平和血清碱性磷酸酶（ＡＫＰ）活性。结果表明，低碘组（Ｉ－Ｓｅ＋，Ｉ－Ｓｅ－）甲状腺重量明显增高，血清Ｔ４下降，Ｔ３变化不明显或代偿性升高。在低碘条件下低硒，１２周时甲状腺重量增加快于低碘加硒组，但是在３２周时，甲状腺重量虽然继续增加，其速度却明显慢于低碘加硒组。血清ＡＫＰ无论１２周还是３２周时，酶活性明显下降仅发生在低碘同时伴有低硒时（Ｉ－Ｓｅ－），当低碘加硒时（Ｉ－Ｓｅ＋），ＡＫＰ活性明显增加且与加碘组（Ｉ＋Ｓｅ＋，Ｉ＋Ｓｅ－）无显著性差别。上述结果提示，缺碘是造成甲状腺肿大的主要原因，缺硒１２周时具有加重甲状腺肿大的辅助作用。     

轻、中度碘过量对碘缺乏大鼠甲状腺功能和形态的影响

目的探讨轻、中度碘过量对碘缺乏Wistar大鼠甲状腺功能和形态影响。方法碘缺乏大鼠以饮用1%过氯酸钾溶液制备,分成0μg/L、840μg/L和1680μg/L碘组。双蒸水(DDW)组饲以DDW和普通饲料。固相免疫放射法(IRMA)测定血清TSH,放射免疫法(RIA)测定血清TT3、TT4、rT3和甲状腺组织TT4。光镜、电镜下观察甲状腺形态学变化。图像分析系统测量大鼠滤泡上皮细胞高度和滤泡腔的面积。结果补碘90天时,碘过量组血清TSH明显低于低碘对照组(均P<0.05),但与DDW组相比差异无显著性。1680μg/L碘组血清TT3值明显低于低碘对照组和DDW(均P<0.05),碘过量组血清TT4值明显高于低碘对照组和DDW组(均P<0.001),血清rT3高于低碘对照组和DDW组,但是差异无显著性,碘过量组甲状腺组织TT4含量明显高于低碘对照组和DDW组(均P<0.001)。甲状腺的相对重量均明显高于DDW组和低碘对照组(P<0.001和P<0.05)。碘过量组随着时间延长,滤泡上皮变扁,滤泡周围毛细血管逐渐减少,巨滤泡形成,同时有部分滤泡增生。碘过量组非增生滤泡上皮细胞高度明显小于DDW组和低碘对照组(均P<0.001),1680μg/L碘组泡腔面积明显大于DDW组和低碘对照组(均P<0.001)。结论轻、中度过量碘(尿碘中位数,MUI为300和600μg/L)处理90天,使碘缺乏大鼠甲状腺功能亢进,低碘致甲状腺肿不能完全恢复,甲状腺滤泡异质性增加。     

The effects of iodine deficiency on thyroid hormone deiodination.

Iodine deficiency induces multiple intrathyroidal autoregulatory changes leading to an increased triiodothyronine (T(3)) production and secretion, at the expense of thyroxine (T(4)). It is characterized by low serum T(4), normal or slightly elevated T(3), and as a consequence of the latter, normal thyrotropin (TSH). Tissues are also hypothyroxinemic, but their T(3) concentrations are mostly normal and ensure clinical euthyroidism, except for those that depend to a high degree on local generation from T(4) by extrathyroidal mechanisms involving the iodothyronine deiodinases isoenzymes. Thus, unless iodine deficiency is so severe and chronic that intrathyroidal and extrathyroidal mechanisms are no longer sufficient to maintain a normal T(3) in most tissues, individuals are clinically and biochemically euthyroid, but some tissues may be selectively hypothyroid (i.e., the brain). In adults both the intrathyroidal and the extrathyroidal mechanisms reacting to the iodine deficiency are fully operative even when the latter is mild. They contribute jointly to the maintenance of elevated or normal T(3) in those tissues deriving most of it from the plasma, until iodine deficiency becomes very severe. Those depending to a large extent from local generation from T(4), mostly by an interplay between type 2 iodothyronine deiodinase (D2) and type 3 (D3), may already be T(3)-deficient (and hypothyroid) with mild iodine deficiency. Therefore, thyroid status of the iodine-deficient individual not only depends on the degree of iodine shortage, but is mostly tissue-specific, and is difficult to define for the individual as a whole: elevated, normal, and low concentrations of T(3) are found simultaneously in different tissues of the same animal, even with severe deficiencies. Most effects of iodine deficiency are reversed in the adults with an adequate iodine prophylaxis, but the absence of T(4) during early fetal life leads to irreversible brain damage (neurologic cretinism). Thyroid hormones of maternal origin are available to the embryo early in development and continue contributing to fetal thyroid hormone status, even after onset of fetal thyroid secretion. In the case of congenital hypothyroidism and normal maternal T(4), the transfer of the latter, together with increased D2 activity, protects the fetal brain from T(3) deficiency, even when it may be insufficient to maintain euthyroidism in other fetal tissues. Practically all of the T(3) found in the fetal brain is derived locally from T(4), and not from circulating T(3). In the case of severe iodine deficiency, both the embryo and the mother are T(4)-deficient; therefore, the fetal brain is exposed to T(3)-deficiency, both before and after onset of fetal thyroid function. This leads to irreversible alterations and damage to the central nervous system (i.e. abnormal corticogenesis). Moreover, because intrathyroidal autoregulatory mechanisms are not yet operative in the fetus, both T(4) and T(3) continue to be very low until birth, and the fetus is not only hypothyroxinemic, similar to its mother, but also clinically and biochemically hypothyroid.     

碘硒缺乏对大鼠脑组织抗氧化能力的影响

按２×２析因实验设计将Ｗｉｓｔａｒ大鼠随机分为４组：Ｉ￣＋Ｓｅ￣＋，Ｉ￣＋Ｓｅ￣－，Ｉ￣－Ｓｅ￣＋，Ｉ￣－－Ｓｅ￣－组，观察了碘硒两种因素对１２周、３２周成鼠及１５日、３０日仔鼠大脑４种抗氧化酶（ＧＰｘ，ＳＯＤ，ＧＳＴ，ＣＡＴ）活力及ＬＰＯ含量的影响。结果表明，缺碘可使成鼠脑ＳＯＤ、ＣＡＴ活力增高，但随着缺碘延长，ＳＯＤ、ＧＰｘ呈下降趋势；除ＧＰｘ外Ｓｅ因素对其它酶无影响，ＧＳＴ各组无变化；缺碘仅使仔鼠（哺乳期）脑ＣＡＴ活力增高，而对其它酶无影响：ＧＰｘ活力在３０日开始受Ｓｅ水平影响；无论成鼠还是仔鼠，缺碘均使脑ＬＰＯ含量明显增高，缺Ｓｅ有增高ＬＰＯ趋势。结果提示，长期缺碘，成鼠腋组织可以发生自由基损伤，而仔鼠脑损伤可能更为严重。