甲状腺功能低下与亢进大鼠模型的几项生化指标的检测

目的:探讨甲状腺功能低下(甲低)及甲状腺功能亢进(甲亢)模型大鼠的甲状腺功能改变对血钙和血磷的影响。方法:制备甲低及甲亢大鼠模型,测定其血清T3、T4、TSH、钙、磷的含量变化。结果:甲低大鼠血清T3、T4和TSH浓度分别为0.27±0.08nm o l/L、25.87±2.83nm o l/L和3.36±0.42mU/L,与对照组血清T3(0.97±0.11nm o l/L)和T4(68.74±7.57nm o l/L)相比较,均明显降低(P<0.0001),有极显著差异;而血清TSH较对照组TSH含量(1.72±0.43mU/L)显著升高(P<0.0001)。甲亢大鼠T3(9.24±1.56 nm o l/L)和T4(155.73±13.98nm o l/L)含量比对照组均显著升高(P<0.0001),而TSH含量仅为0.37±0.06mU/L,与对照组相比明显降低(P<0.0001)。对照组血钙(C a2+)和血磷(HPO42-)含量分别为2.37±0.30mm o l/L和2.56±0.10mm o l/L;甲低组血钙为2.27±0.15mm o l/L,血磷为2.33±0.10mm o l/L;甲亢组血钙含量为6.17±1.42mm o l/L,血磷含量为3.84±1.13mm o l/L。结论:甲亢大鼠血钙和血磷含量较正常大鼠明显升高。甲低大鼠血清钙、磷含量与对照组大鼠比较均有所下降,但无统计学意义。     

甲状腺素对大鼠脂肪组织解偶联蛋白 2基因表达的影响

目的：探讨甲状腺素对大鼠白色脂肪组织(WAT)解偶联蛋白 2(UCP2)基因表达的影响.方法：正常雄性Wistar大鼠30只,随机分为3组,对照组、甲状腺功能亢进(甲亢)组和甲状腺功能低下(甲低)组,每组10只,应用左甲状腺素钠和甲巯咪唑分别造成大鼠甲亢和甲低状态;用放射免疫法检测血清总三碘甲状腺原氨酸(T3)、甲状腺素(T4)的浓度;半定量RT PCR法检测WAT中UCP2 mRNA的表达水平.结果：与对照组相比,甲亢组大鼠WAT中UCP2 mRNA的水平增加1.4倍,甲低组大鼠WAT中UCP2 mRNA的水平降低20%(均P＜0.01).结论：甲状腺素对WAT中UCP2基因的表达具有上调作用     

Plasma and urinary digoxin in thyroid dysfunction

Summary The response to a single oral dose of 0.5 mg digoxin has been studied in eight patients, of whom four were hyperthyroid and four were hypothyroid, both before and after treatment for their thyroid dysfunction. The post-dose plasma digoxin levels were significantly lower in the hyperthyroid patients when they were thyrotoxic than when they became euthyroid. In only one hypothyroid patient was the post-dose plasma digoxin level significantly higher before treatment than it was after and in the others the digoxin values reached were either the same as, or lower than, before treatment. There was a significant correlation between the creatinine clearance and the urinary concentrations of digoxin and these both altered with change in thyroid status. Total urinary digoxin excretion did not change. Pharmacokinetic analysis suggested that digoxin was distributed in a way compatible with a two-compartment model and that the volume of the central compartment was high in thyrotoxic patients and low in hypothyroid patients. In both cases it reverted to a median value after treatment. It is recommended that plasma digoxin levels should be monitored in all patients with thyroid dysfunction who require therapeutic digoxin.     

Influence of thyroid hormone on the phospholipid composition of lung tissue and surfactant of rats

Thyroid hormone is an important regulator of lipid metabolism in vivo. The effect of thyroid hormone on the phospholipid composition of lung tissue and surfactant has been studied in hypothyroid and hyperthyroid rats in comparison with the control rats. Rats were made hyperthyroid by administering 1 mg of L-thyroxine/kg body weight for six days. Another group of rats was rendered hypothyroid by injecting 1 mci of Na I131 to each rat. Phosphatidyl choline, lysophosphatidyl choline, lysophosphatidyl ethanolamine, phosphatidyl ethanolamine, and sphingomyclin, were estimated by thin layer chromatography. A decrease in phospholipids in hypothyroid and an increase in the hyperthyroid rats was observed. This can be attributed to the altered thyroid activity.     

Oxazepam pharmacokinetics in thyroid disease.

The pharmacokinetics of oxazepam, a drug mainly eliminated by a single step glucuronidation reaction, were studied in seven hyperthyroid and six hypothyroid patients before and after treatment. Oxazepam elimination half-life was shorter and apparent oral clearance higher in untreated hyperthyroid patients than after treatment. There was no significant change in oxazepam elimination in hypothyroid subjects. Time to peak concentration (tmax) was reduced in the hyperthyroid state. Hypothyroidism had no significant effect on tmax. Serum bilirubin concentration was lower in the patients while hyperthyroid before treatment than when euthyroid and also lower than in the hypothyroid patients. There was no significant correlation between serum bilirubin concentrations and oxazepam elimination. These results suggest that glucuronyl transferase activity is increased in hyperthyroidism but is not altered in most patients with hypothyroidism. The extent of increase in glucuronyl transferase activity is similar to that produced by enzyme inducing drugs.     

The effect of thyroid dysfunction on the chronotropic response to noradrenaline

Dose-response curves to noradrenaline in the presence and absence of beta-receptor antagonists were established with isolated atria from euthyroid, hypothyroid and hyperthyroid rats. Baseline atrial rate and Emax were significantly lower than normal in the hypothyroid group and significantly higher than normal in the hyperthyroid group. Differences between the groups were minimal for pD2 and range of response to noradrenaline. The response to beta-receptor antagonists was the same in all 3 groups with the exception of the hypothyroid group which showed an attenuated increase in baseline atrial rate with compounds possessing partial agonist activity. This was particularly marked for practolol. These results do not provide evidence for an altered responsiveness to catecholamines due to altered thyroid status but suggest that thyroid hormones have a direct action on cardiac tissue.     

Influence of altered thyroid state on the inotropic potency of isoproterenol--studies with isolated rat left atria paced at different frequencies

The influence of thyroid status upon the inotropic effect of isoproterenol has been examined using left atrial preparations isolated from hypothyroid, control (untreated), and hyperthyroid rats. Atria were paced at 5 Hz with submaximal field pulses, and isoproterenol was added cumulatively. Mean maximum inotropic responses to isoproterenol were 1.4 mN (hypothyroid), 1.2 mN (control), and 0.3 mN (hyperthyroid). Analysis of log concentration-fractional response curves revealed that isoproterenol was approximately 10 times less potent in preparations from hypothyroid rats. In preparations from hyperthyroid rats, the potency of isoproterenol was similar to that observed in control preparations. These results cast doubt upon the functional significance of the increased responsiveness to isoproterenol observed in other studies in which atria were paced at low frequencies. When applied at a concentration approximating the appropriate EC50 to atria paced at varying frequencies (1, 3, 5, and 5.8 Hz), isoproterenol enhanced contractile force developed in response to stimulation at the lower frequencies in atria from hypothyroid rats, and depressed the response of atria from hyperthyroid rats to stimulation at the higher frequencies.     

Effect of altered states on liver and kidney uptake of 109Cd in rats.

Hypothyroid and hyperthyroid states were induced in rats by drug treatment with propylthiouracil and thyroxine, respectively. The thyroid states were verified by measuring serum thyroxine using a commercial competitive protein-binding technique. A single ¹⁰⁹Cd ip injection was then given to three groups: hypo-, eu-, and hyperthyroid. The uptake of ¹⁰⁹Cd in liver and kidneys was measured at times ranging from 1 to 120 hr. On a per gram basis, ¹⁰⁹Cd uptake in livers and kidneys of hypothyroid rats was significantly greater than that of eu- and hyperthyroid rats, even though there was a dwarfing effect in the hypothyroid group. The transfer of ¹⁰⁹Cd from the liver to the kidneys was not affected by the altered thyroid states.     

Pharmacokinetics of theophylline in hyperthyroid and hypothyroid patients with chronic obstructive pulmonary disease

Summary The pharmacokinetics of theophylline was investigated in five hyperthyroid, five hypothyroid, and five euthyroid patients, all with chronic obstructive pulmonary disease. Wide individual variability was found in theophylline kinetics, but the rate of elimination of theophylline was significantly higher in hyperthyroid, and lower in hypothyroid patients than in the euthyroid patients (k_el=0.155, 0.060 and 0.107 h^–1, respectively). The values for clearance and volume of distribution were not consistently changed compared with those in the euthyroid group, although all the parameters except AUC were significantly different in hyperthyroid and hypothyroid patients. There was a positive correlation between both thyroxine and triiodothyronine serum concentrations and total body clearance of theophylline (r=0.795 and r=0.791, respectively). It is concluded that in spite of the wide interindividual variability and the relatively small differences in the pharmacokinetics of theophylline in thyroid dysfunction compared with the euthyroid status, these differences have to be considered in certain clinical situations, as they may require changes in the therapeutic regimen for administration of theophylline in hyperthyroid or hypothyroid patients.     

CYCLIC ADENOSINE 3'',5''-MONOPHOSPHATE CONTENT AND BRONCHIAL SMOOTH MUSCLE CONTRACTILITY OF HYPER- AND HYPOTHYROID LUNGS

1. Male Sprague-Dawley rats were made either hyper- or hypothyroid with thyroxine or 4-methyl-2-thiouracil, respectively. Bronchial smooth muscle (BSM) contractility and lung cyclic adenosine 3',5'-monophosphate (cAMP) content were measured in both conditions. 2. Bronchial smooth muscle contractility was significantly weaker in hyperthyroid rats, while the BSM contractility of hypothyroid rats was the same as controls. 3. The cAMP content of hyperthyroid rat lungs was similar to controls but was decreased in hypothyroid rats. 4. These studies demonstrated that both the hyper- and hypothyroid states affect respiration, although the mechanisms involved with different for each condition.     

Oxidative stress induced by thyroid dysfunction in rat erythrocytes and heart

The aim of this study was to determine whether the effects of thyroid dysfunction induce oxidative stress in the blood and heart of male Wistar rats. Rats were randomly divided into three groups: group I served as control rats. Group II was treated daily with 0.05% benzythiouracile (BTU) administered in drinking water. Rats of group III have received l-thyroxine sodium salt (0.0012%), in drinking water. The results showed that thyroid dysfunction rats had poor growth performance. On the other hand, in hyperthyroid rats, a marked decrease compared with control occurred of some hematological parameters such red blood cell number (RBC), haemoglobin (Hb) concentration and haematocrit (Ht). There was also a significant increase in erythrocyte numbers and heart TBARS concentrations in hypothyroid rats compared with control. These results were associated with a fall in the total antioxidant status (TAS) in the serum of the hyperthyroid rats. Alteration of the antioxidant system in the hypo-/hyperthyroidism-induced rats was confirmed by the significant increase of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities and a decline in glutathione (GSH) content in both tissues were detected in hyperthyroid group compared to controls. On the other hand, serum transaminase activities (aspartate transaminase (AST); alanine transaminase (ALT)) were elevated indicating hepatic cellular damage after treatment with exogenous L-thyroxine. Moreover, serum lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT) and creatine phosphokinase (CPK) activities were increased in the hyperthyroidism rats. These results indicated that excessive thyroxin (long term) ingestion had an adverse effect on animal health and performance. We conclude that thyroid dysfunction induces oxidative stress and modifies some biochemical parameters of erythrocytes, heart and liver disease; our results show the occurrence of a state of oxidizing stress in relation to hyperthyroidism.     

Digoxin-desethylamiodarone interaction in the rat: comparison with the effects of amiodarone

We have shown that there is a pharmacokinetic interaction between amiodarone and digoxin that results in an increase in steady-state serum and tissue concentrations of digoxin in rats. There is a linear correlation between serum levels of amiodarone, as well as desethylamiodarone, and steady-state serum digoxin levels in rats treated with amiodarone. Since desethylamiodarone is formed in amounts equal to that of the parent compound during chronic amiodarone therapy, we investigated the possibility of desethylamiodarone directly interacting with digoxin in rats. Rats that received digoxin alone showed a serum level of 0.32 +/- 0.08 ng/ml, whereas those that received combination therapies showed a serum level of 3.25 +/- 1.06 ng/ml (p less than 0.001) with desethylamiodarone administration, and 3.00 +/- 0.87 ng/ml with amiodarone administration. Concomitant administration of desethylamiodarone and digoxin increased digoxin concentration in the myocardium by 110% (p less than 0.001), in the skeletal muscle by 208% (p less than 0.001) and in the brain by 110% (p less than 0.001). The corresponding figures for amiodarone-digoxin administration were 94% (p less than 0.001), 172% (p less than 0.001) and 80% (p less than 0.001). The tissue/serum ratios of digoxin concentrations in the myocardium, skeletal muscle, and brain were decreased in the rats that received combination therapies, indicating reduced tissue binding of digoxin. The data indicate that desethylamiodarone interacts with digoxin in a manner similar to that of the parent compound.     

Effects of dantrolene on force development in slow- and fast-twitch muscle of euthyroid, hypothyroid, and hyperthyroid rats.

1 The effects of dantrolene on twitch and tetanic force development were determined in soleus and gastrocnemius muscle of euthyroid, hypothyroid, and hyperthyroid rats. 2 Maximum twitch force of the gastrocnemius muscle was significantly more depressed by dantrolene than that of the soleus muscle in euthyroid and hyperthyroid rats. In hypothyroid rats, the effect of dantrolene on maximum twitch force was similar in soleus and gastrocnemius muscle. 3 Maximum tetanic force in soleus and gastrocnemius muscle was less depressed by dantrolene than the twitch force in either thyroid state. The effect of dantrolene on maximum tetanic force increased in both muscles in the direction hypothyroid----euthyroid----hyperthryoid. 4 The results are discussed in terms of an effect of thyroid hormones on Ca2+ -cycling during force development, as a result of thyroid hormone-induced proliferation of the sarcoplasmic reticulum.     

甲亢和甲减患者血脂和载脂蛋白的变化

本文观察35例Graves 甲亢(GD)和20例甲状腺功能减退(甲减)患者药物治疗前后血脂和载脂蛋白(APO)的变化,GD 患者治疗前血清总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)和APOB 均明显降低,经抗甲状腺药物(ATD)治疗甲亢缓解后,上述指标恢复正常。治疗前后GD 患者血清甘油三脂(TG)及APOA 浓度无明显变化。治疗前血清TC、APOB 浓度与T_3,T_4水平呈负相关。甲减患者治疗前血清TC、TG 和LDL-C 高于对照组,替代治疗后,其浓度降至正常。患者APOB 浓度比治疗前下降,但治疗前后血清HDL-C 和APOA 水平无显著变化。治疗前血清T_c与血清T-3、T_4浓度呈负相关。     

The effect of thyroid state on the distribution of ethanol in experimental ethanol poisoning

Hyperthyroidism increases the mortality of rats to ethanol poisoning, but the exact mechanism has not yet been established. In the present study, rats were protected against ethanol poisoning by hypothyroidism. The rate of absorption of a single large oral dose of ethanol from the gastrointestinal tract was increased in hyperthyroid and decreased in hypothyroid animals. At death, the ethanol levels in the cerebrospinal fluid were lower in hyperthyroid rats than in hypo- and euthyroid ones. The equilibration was influenced by both the dose of ethanol and the thyroid state. The results demonstrate that the blood concentrations cannot be used to estimate the functionally important ethanol concentrations affecting the vital neural centers of the brain before the equilibration of ethanol is completed. The lethal blood concentrations of ethanol for rats are probably not different from those for humans.     

Monoamine concentrations changes in the PTU-induced hypothyroid rat brain and the ameliorating role of folic acid

Thyroid hormones are recognized as the key metabolic hormones that play a critical role in the development of central nervous system (CNS) throughout life. The present study was designed to determine the changes in brain monoamine concentrations in 6-n-propyl thiouracil (PTU)-induced hypothyroid rats, in addition to the ameliorating role of folic acid treatment. Fifty male albino rats were equally divided into five groups; first and second groups were the control and folic acid groups, respectively, while the third group was the hypothyroid group in which the rats received PTU in drinking water for 6 weeks. The fourth and fifth groups were co- and post-treated folic acid groups with hypothyroid rats, respectively. Our results revealed that serotonin and norepinephrine concentrations were significantly decreased in the hypothalamus and cortex, while it significantly increased in the hippocampus of hypothyroid rats when compared with control group. Serotonin and norepinephrine concentrations were decreased in hypothalamus and cortex in co- and post-treated folic acid groups with hypothyroid rats, while the concentration of dopamine were significantly increased in the hypothalamus and hippocampus of the hypothyroid rats and co-treated folic acid group with hypothyroid rats. In cortex, the dopamine concentration was significantly increased in hypothyroid rats and post-treated folic acid group with hypothyroid rats, while it significantly decreased in co-treated folic acid group with hypothyroid rats when compared with the control group. Also, our results revealed that, folic acid treatment was better if it is administered as an adjuvant after returning to the euthyroid state by withdrawing PTU from the drinking water.     

丙基硫氧嘧啶联用卡托普利对甲亢大鼠心肌的保护作用

目的研究卡托普利对甲亢大鼠心肌的保护作用。方法大鼠ig左甲状腺素钠片14 d,测定血清中FT3、FT4、TSH,制作大鼠甲亢模型;分组给药治疗14 d后,再次测定大鼠血清中FT3、FT4、TSH,并检测大鼠心肌MDA的含量、SOD和GSH-PX酶的活性。结果丙基硫氧嘧啶、卡托普利、丙基硫氧嘧啶联合卡托普利3组均可降低大鼠血清中FT3、FT4,升高TSH;丙基硫氧嘧啶及卡托普利单独给药具有降低MDA含量、升高SOD活性的趋势;丙基硫氧嘧啶 卡托普利给药可显著降低心肌MDA含量,升高SOD、GSH-PX酶活性(P<0.01)。结论给予卡托普利后,较单纯丙基硫氧嘧啶抗甲亢治疗具有明显的心肌保护作用。     

Amiodarone-digoxin interaction in rats. A reduction in hepatic uptake

The interaction amiodarone-digoxin results in a marked increase in the digoxin serum concentrations. The mechanism of this interaction is still unexplained. The influence of amiodarone on digoxin hepatic extraction in rats was investigated. The digoxin hepatic extraction coefficients were determined using the isolated-perfused livers of control and amiodarone-treated (25, 50, and 100 mg/kg/day for 5 days) rats. When plotted as a function of time, an inverse relationship between the extraction coefficients and the dose of amiodarone was evident. Significant dose-related reductions were observed in hepatic clearances calculated after 16 and 20 min of digoxin infusion when steady state was achieved. Analysis of the hepatic effluent by HPLC revealed only digoxin in the effluent of both control and amiodarone-treated rats; no metabolites were detected. Using liver homogenates, no differences were found in the ability of control or amiodarone-treated (50 mg/kg/day for 5 days) rats to metabolize digoxin. These changes occur without significant lesion of the hepatocytes, inasmuch as the serum concentrations of glutamic-pyruvic and glutamic-oxaloacetic transaminases were not affected by the administration of amiodarone (50 or 100 mg/kg/day for 5 days). Furthermore, a microscopic study of the hepatocytes revealed light cytoplasmic vacuolization, normal Kupffer cells, and no evidence of macrophage proliferation. It was concluded that amiodarone increases digoxin serum concentrations by inhibiting its uptake into the hepatocytes.     

Hypothyroidism protects di(n-butyl) phthalate-induced reproductive organs damage in Sprague-Dawley male rats

This study examined the deleterious effects of di(n-butyl) phthalate (DBP) on the male reproductive organs in hypothyroid rats. Hypothyroidism was induced in prepubertal male rats (28 days of age) by an intraperitonial (i.p.) injection of 10 mg/kg/day propylthiouracil (PTU) for 30 days. DBP (100 and 500 mg/kg/day) was administered by oral gavages to the intact or hypothyroid rats for 30 days. The body weight of the PTU-treated rats was significantly lower than the control group. The total triiodothyronine (T3) and thyroxine (T4) serum level was lower, and the thyroid-stimulating hormone (TSH) level was higher in the hypothyroid rats than in the control rats. The DBP treatment rats showed significantly lower testes, epididymides, seminal vesicles, and ventral prostate weights than the untreated rats. The hypothyroid rats had significantly higher thyroid weights and lower adrenal glands weights than the control rats. The histomorphological examination showed diffused Leydig cells hyperplasias and germ cells loss in the DBP (500 mg/kg)-treated rats, whereas these effects were mild in the DBP-treated hypothyroid rats. The serum levels of monobutyl phthalate (MBP) were significantly lower in PTU-induced hypothyroid rats than in the DBP-treated rats. This data suggests that the hypothyroid status might offer some protection from male reproductive organ toxicity caused by a disturbance in the metabolic activation of the parent compound, DBP.