锌对甲状腺功能低下大鼠肝细胞核T3受体的影响

目的探讨补锌对甲状腺功能低下大鼠肝细胞核T3受体特性的影响。方法用低碘饲料喂养诱导大鼠甲状腺功能低下,采用T3和离体肝细胞核结合实验方法,观察补锌对甲状腺功能低下大鼠肝细胞核T3受体的影响。结果甲状腺功能低下大鼠肝细胞核T3受体的亲合常数(Ka)增加(P<0.01),最大结合容量(MBC)明显下降(P<0.01)。补锌后血清T3、T4水平未见明显改变(P>0.05),肝细胞核T3受体的Ka值降低(P<0.05),MBC增加(P<0.05),T3受体占位率无明显改变(P>0.05)。结论补锌可通过调节肝细胞核T3受体的结合容量改善甲状腺功能低下大鼠的甲状腺功能。     

实验性甲状腺功能低下大鼠肝核 T_3受体的变化及其与肝α-磷酸甘油脱氢酶的关系

本文采用 T_3与离体肝细胞核结合实验的方法,探讨甲低功大鼠肝核 T_3受体的变化及其与肝α-磷酸甘油脱氢酶(α-GPD)之间的相互关系。结果表明,甲低功大鼠肝核 T_3受体的亲合常数(Ka)明显增加,最大结合容量(MBC)明显下降,肝α-GPD 与 MBC 之间呈正相关。提示核 T_3受体的结合容量受甲状腺激素的调节与控制。在不同的甲功状态下,T_3通过调节自身受体蛋白的合成进而诱导α-GPD 等酶的活性。     

人胎儿脑细胞核T3及其受体的个体发生

本文报告了对胎儿脑细胞核T_3及其受体的个体发生进行的系统研究实验结果。实验结果表明:(1)胎儿的大、小脑细胞核受体对T_3的亲和常数(Ka)值不因脑区不同或发育阶段不同而有显著差别;(2)胎儿大、小脑细胞核T_3受体的最大结合容量(MBC)值有所不同,但均随孕龄增加而增高,且各呈线性相关;(3)胎儿脑细胞核内源T_3含量(总量及受体结合形式者)随发育而增高,且与受体MBC值的增长显著相关;(4)受体占位率不随发育而改变。     

甲状腺功能减退大鼠脑海马组织T3核受体基因表达

目的了解甲状腺功能减退(简称甲减)大鼠海马组织T3核受体(T3NR)α、β亚型mRNA的特异性变化,探讨甲状腺激素对脑发育及功能调控的分子机制。方法采用丙基硫氧嘧啶(PTU)腹腔注射诱发甲减动物模型,运用RT-PCR检测技术测定实验性甲减大鼠脑海马组织T3NRα1mRNA、T3NRβ1mRNA的表达水平。结果甲减大鼠海马组织T3NRα1mRNA、T3NRβ1mRNA的表达水平明显下调,与正常对照组比较差异有统计学意义(P<0.01)。结论甲减时脑组织T3NRα、β亚型mRNA的表达水平下调,T3NR的合成减少,导致甲状腺激素的生物效应的降低,可能是甲减性脑损害发生的重要病理机制之一。     

锂对甲状腺功能影响的初步观察

锂作为致甲状腺肿的物质,愈来愈多地受到人们的重视。本试验的结果表明服锂后血清T_4下降,T_3升高,T_3/T_4比值增高,其差异都非常显著。服锂组与对照组尿碘无差异性。     

甲状腺功能低下大鼠中枢5-HT对TSH分泌的影响

目的 探讨甲状腺功能低下（甲低）大鼠中枢５－羟色胺（５－ＨＴ）系统的代谢变化与机制,以及５－ＨＴ对促甲状腺激素（ＴＳＨ）分泌的调节作用。方法 用０．５％ＮａＣＩＯ４诱导实验大鼠甲低功,采用荧光分析方法测定大鼠脑组织５－ＨＴ、５－ＨＩＡＡ含量及ＭＡＯ活性,放免法测定血清Ｔ３、Ｔ４及ＴＳＨ含量。结果 甲低组大鼠血清Ｔ３、Ｔ４含量明显下降,而血清ＴＳＨ含量及脑组织中５－ＨＩＡＡ、５－ＨＩＡＡ／５－ＨＴ比     

甲状腺功能异常患者末梢血淋巴细胞T3核受体基因表达

为了解甲状腺功能异常患者末梢血淋巴细胞Ｔ３核受体基因表达情况，以人ｃ－ｅｒｂＡα和ｃ－ｅｒｂＡβ的ｃＤＮＡ片段为探针，应用分子杂交技术，检测了５例Ｇｒａｖｅｓ病和７例桥本甲状腺炎伴甲状腺功能减退患者末梢血淋巴细胞ｃ－ｅｒｂＡα和ｃ－ｅｒｂＡβｍＲＮＡ的相对含量。结果表明：人淋巴细胞ｃ－ｅｒｂＡαｍＲＮＡ有６．０ｋｂ和３．２ｋｂ两种形式，而ｃ－ｅｒｂＡβｍＲＮＡ有５．０、３．０和２．０ｋｂ三种形式。桥本甲状腺炎伴甲状腺功能减退患者末梢血淋巴细胞ｃ－ｅｒｂＡα和ｃ－ｅｒｂＡβｍＲＮＡ表达增强，但Ｇｒａｖｅｓ病患者无明显变化。提示：桥本甲状腺炎伴甲状腺功能减退患者血清甲状腺激素水平减低，对其末梢血淋巴细胞Ｔ３核受体亚型在基因转录水平有向上调节作用。     

对新生儿甲状腺功能低下症筛查的讨论

对新生儿甲状腺功能低下症筛查的讨论王振华，赵玉英自１９７１年建立新生儿甲状腺功能低下症筛查（简称甲低筛查）以来，包括中国在内的许多国家开展了这项工作，取得了十分明显的社会经济效益。并日益显示出筛查在评价碘缺乏病防治效果和人群危害程度的现实意义。我们自...     

生命周期中大鼠脑细胞核T3受体的个体发生

对大鼠自出生至衰老(生后1天～18个月)各阶段脑细胞核提取液中内源T_3(EnT_3-KMT)水平及T_3受体的亲和常数(K_a)和最大结合容量(MBC)进行了观察和分析。结果:大脑与小脑细胞核T_3受体的各自K_a和MBC不随年龄及性别而改变,但大脑的K_a及MBC均为小脑的2倍。大、小脑细胞核提取液中的内源T_3在2月龄为高值,以后随年龄增高而下降,至老年略有回升。大脑内源T_3浓度亦为小脑的2倍。同龄、同性别大鼠的大、小脑T_3受体占位率基本相同,并随年龄增高而降低。     

甲状腺功能减退对慢性肝病的影响

正常生理状态下,肝脏在甲状腺激素的代谢、降解和排泄过程中发挥着重要作用。但当肝脏发生病变时,甲状腺功能减退现象明显增加,且多数患者无明显临床症状及体征。归纳了由于各种病因引起的慢性肝病及其不同发病阶段患者甲状腺功能水平的变化,发现甲状腺激素水平的下降对预测慢性肝病发生风险、病情判断及预后评估具有重要的指导价值。研究认为部分慢性肝病患者可通过甲状腺功能的调节,进而在一定程度上起到缓解病情、改善预后的治疗效果。此外,由于甲状腺代谢异常所引发的一系列基因失调或功能紊乱有可能成为部分慢性肝病新的治疗靶点,结论有待进一步研究证实。     

肝脏X受体调控小鼠心肌细胞肥大性生长

目的 研究肝脏X受体(LXR)在肥厚心肌中表达的变化及其对心肌细胞肥大性生长的影响.方法 8周龄的野生型小鼠随机分为2组,即手术组和假手术组.两组小鼠分别接受主动脉缩窄术或假手术,术后2周进行各项指标检测,如心脏重/体重、心肌组织病理检测、分子生物学检测等;同时进行乳鼠心肌细胞体外培养,用血管紧张素(Ang)Ⅱ诱导心肌细胞肥大性生长,并与LXR激动剂T0901317共孵育,通过检测心肌细胞蛋白质合成率、分析细胞形态及肥大基因表达等,探讨LXR对体外心肌细胞肥大性生长的调控作用.结果 病理及分子生物学检测证实主动脉缩窄术成功的构建了心肌肥厚的小鼠模型.手术组小鼠心肌组织中LXRα的蛋白及mRNA表达均显著高于假手术组(P均<0.05),而LXRB的表达差异无统计学意义.体外研究表明,LXR激动剂T0901317呈剂量依赖性地抑制由AngⅡ诱导的心肌细胞肥大,表现在T0901317治疗组的心肌细胞面积、肥大基因的表达量、蛋白质合成率等均低于空白对照组(P均<0.05).结论 LXR是心肌肥厚的重要调控因子,LXR的激活能负性调控心肌细胞肥大性生长.     

Vitamin D3 modulates T lymphocyte responses in hepatitis C virus-infected liver transplant recipients

Background

Aim of the present study was to investigate whether 1,25(OH)(2)D(3) (Vitamin D3) modulates T lymphocyte functions in patients transplanted for hepatitis C virus-related cirrhosis.

Methods

Sixteen patients and ten healthy subjects were investigated. T lymphocytes were activated in vitro in the presence or absence of Vitamin D3 and then the proliferative response and IFN-γ and TNF-α production were assessed.

Results

Vitamin D3 potently reduced T-lymphocyte proliferation in a dose-related fashion. Similarly, FACS analysis and ELISA testing demonstrated that Vitamin D3 significantly decreased the response frequency and the response intensity of IFN-γ and TNF-α production in the whole CD3-positive T lymphocyte population as well as in “naive” CD4+ CD45RA+ and “memory” CD4+ CD45RO+ T lymphocyte subsets. The inhibitory effect of Vitamin D3 on T-cell proliferation and cytokine production was not different between patients and controls. No toxic effects were exerted by Vitamin D3 even at the higher concentration used (10 nM). Finally, no statistically significant correlation was found between 25(OH)D serum levels and the proliferative response or cytokine production of T lymphocytes from transplanted patients.

Conclusions

This study demonstrates that in patients transplanted for hepatitis C virus-related cirrhosis Vitamin D3 modulates T lymphocyte activation, and provides a rationale for the evaluation of this compound as an immunosuppressive agent in liver-transplanted patients.     

Effects of the synthetic liver X receptor agonist T0901317 on the growth hormone and thyroid hormone axes in male rats

Liver X receptors (LXRs), activated by oxysterols, play an important role in the regulation of lipid and glucose metabolism, which is also markedly dependent on thyroid hormone and growth hormone (GH) status. Here, we investigated how a 1-week exposure to the synthetic LXR agonist T0901317 affected GH secretion and thyroid hormone status in male rats. While the pulse frequency of GH secretion was marginally affected there was a highly significant decrease in the triiodo-L-thyronine/thyroxine (T3/T4) ratio in plasma. This effect was associated with decreased expression of deiodinase 1 (DIO1) and 2 (DIO2) mRNA in the liver and thyroid gland, respectively. Expression of sterol regulatory element binding protein-1c (SREBP-1c), the hallmark of stimulated lipogenesis, was markedly increased in both thyroid and pituitary implying that protracted pharmacological LXR activation may promote lipid accumulation in these endocrine tissues. These findings suggest that attention must be given to pituitary hormone dependent axes when developing therapeutic strategies based on agonism of the LXRs, e.g. for treatment of atherosclerosis.     

Toll-like receptors in pathophysiology of liver diseases

Toll-like receptors (TLRs) are pattern recognition receptors that participate in host defense by recognizing pathogen-associated molecular patterns alongside inflammatory processes by recognizing damage associated molecular patterns. Given constant exposure to pathogens from gut, strict control of TLR-associated signaling pathways is essential in the liver, which otherwise may lead to inappropriate production of pro-inflammatory cytokines and interferons and may generate a predisposition to several autoimmune and chronic inflammatory diseases. The liver is considered to be a site of tolerance induction rather than immunity induction, with specificity in hepatic cell functions and distribution of TLR. Recent data emphasize significant contribution of TLR signaling in chronic liver diseases via complex immune responses mediating hepatocyte (i.e., hepatocellular injury and regeneration) or hepatic stellate cell (i.e., fibrosis and cirrhosis) inflammatory or immune pathologies. Herein, we review the available data on TLR signaling, hepatic expression of TLRs and associated ligands, as well as the contribution of TLRs to the pathophysiology of hepatic diseases.     

Effect of neonatal hypothyroidism on maturation of nuclear triiodothyronine (T3) receptors in developing rat brain

Changes of nuclear T3 receptors during brain maturation were studied in normal and hypothyroid rats. In normal rats, the higher receptor concentration present in the neonatal period (0.35 +/- 0.04 ng T3/mg DNA) decreased at the age of 14 days (0.25 +/- 0.02 ng T3/mg DNA), and remained at this level thereafter to 35 days of age (0.25 +/- 0.03 T3/mg DNA). In contrast, hypothyroid rats showed a significantly higher concentration than that found in an age-matched control group at the age of 14 days (0.38 +/- 0.07 ng T3/mg DNA), and maintained this level up to 35 days of age (0.37 +/- 0.03 T3/mg DNA). The binding affinity was similar in both groups and throughout maturation (mean +/- SD in normal groups; 1.9 +/- 0.3 X 10(10)M-1, in hypothyroid groups: 1.7 +/- 0.2 X 10(10)M-1). Plasma T3 concentrations showed changes reciprocal to those in the binding capacity of T3 receptors. These results indicate that nuclear T3 receptors in rat brain mature by the age of 14 days, in association with a decrease in binding capacity, and this process seems to be T3-dependent. The physiological role of the high concentration of T3 receptors observed in neonatal and hypothyroid rat brain during development is at present not clear.     

自然杀伤T淋巴细胞与肝脏疾病

自然杀伤T淋巴细胞（natural killer T cells，NKT细胞）是一类同时表达恒定的T淋巴细胞受体（TCR）αβ（人为Vα24／Vβ11，鼠为Vα14／Vβ8）和NK细胞标志的T细胞亚群；主要起源于胸腺，发育成熟过程大多依赖于MHC-Ⅰ类样分子CD1d；主要分布于肝脏、骨髓、胸腺等器官，约占小鼠肝脏内成熟T淋巴细胞（T细胞）的30％，占人类肝脏T细胞的10％，外周血也有少量分布；主要经抗原提呈细胞表面CD1d提呈的糖脂类抗原活化，并迅速地释放大量的IFNγ和IL-4等细胞因子，通过调节Th1／Th2细胞间的平衡，在自身免疫性疾病、抗感染、抗肿瘤等方面发挥重要的作用。近年研究表明，NKT细胞与肝脏疾病关系密切，可能参与了肝炎、肝硬化、肝癌等诸多肝脏疾病的发生与发展。