碘对环孢霉素A抑制免疫性甲状腺炎拮抗作用

目的研究碘过量对环孢霉素A(Cyclosporin A,CsA)抑制实验性自身免疫性甲状腺炎(EAT)形成的拮抗作用,进一步探讨碘在自身免疫性甲状腺炎发病中的作用。方法给予Lewis大鼠不同碘摄入量,EAT诱发组和EAT+CsA组均用猪Tg进行免疫诱发EAT形成,EAT+CsA组于首次免疫后的第10 d开始腹腔注射CsA,5 mg/(kg.d),非EAT对照组不做任何处理,末次免疫后2周处死各组大鼠并取材。观察大鼠甲状腺组织的病理改变和炎细胞浸润程度,采用放射免疫法检测血清中甲状腺球蛋白抗体(TG-Ab)、甲状腺过氧化物酶抗体(TPO-Ab)和T3、T4水平。结果(1)不同碘摄入量的EAT组和EAT+CsA组的大鼠甲状腺组织均有不同程度的炎性细胞浸润,非EAT对照组大鼠甲状腺未见明显炎性细胞浸润。EAT组大鼠甲状腺的炎症反应重于EAT+CsA组,诱发EAT的2组甲状腺的炎症反应随碘摄入量的增加而加重。(2)EAT组和EAT+CsA组的血清中自身抗体TG-Ab和TPO-Ab水平均高于对照组(P<0.05),EAT+CsA组的TG-Ab和TPO-Ab水平均低于EAT组,2组自身抗体水平亦随着碘摄入量的增加有升高趋势。(3)100倍碘水平的各组T4水平下降,各组的血清T3含量比较差异无统计学意义。结论增加碘的摄入量会明显加重EAT的炎症反应,促进EAT的形成和发展;CsA对EAT的形成及甲状腺自身抗体的产生有一定的抑制作用,碘过量可以拮抗CsA的这种作用,且随碘摄入量的增加拮抗效应增强;碘摄入过多可以抑制甲状腺激素的合成和释放。     

碘对自身免疫性甲状腺炎大鼠抗氧化能力影响

目的 探讨不同碘水平对实验性自身免疫甲状腺炎(experimental autoimmune thyroiditis,EAT)大鼠抗氧化活性的影响。方法 选择雌性Lewis大鼠,随机分为4组;于实验第8周处死动物,观察大鼠甲状腺组织的病理变化,测定甲状腺球蛋白抗体(TGAb)、甲状组甲状腺腺微粒体抗体(TMAb),肝和脑组织中谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)活性。结果 各造模组织出现淋巴细胞浸润,高碘时以甲状腺滤泡扩张、融合为主,低碘时以增生为主;高碘+造模组大鼠的TGAb和TMAb水平分别为(75.00±15.44)%,(72.15±15.00)%,明显高于造模组的(63.01±12.36)%,(60.62±11.24)%和低碘+造模组的(58.87±9.57)%,(57.89±9.67)%(P<0.05);低碘组EAT大鼠肝组织GSH-Px和SOD活性最低,分别为(122.01±10.34),(522.81±54.62)U/(mg.prot)(P<0.05)碘过量时脑组织谷胱甘肽过氧化物酶(GPX)活性最低,为(412.09±115.71)U/(mg.prot)(P<0.05)。结论 碘缺乏和碘过量均能够加重EAT大鼠甲状腺的炎性损伤和氧化损伤,其中碘缺乏对EAT大鼠作用明显。     

Bcl-2家族参与碘诱发自身免疫性甲状腺炎小鼠甲状腺细胞凋亡

目的研究Bcl-2家族成员在高碘诱发实验性自身免疫性甲状腺炎(experimental autoimmune thyroiditis,EAT)小鼠甲状腺细胞凋亡中的作用,初步探索自身免疫性甲状腺炎的发病机制。方法选取24只4～5周龄雌性NOD-SCID小鼠,随机分为4组,每组6只:对照组、高碘组、聚肌胞苷-聚胞苷酸[Poly(I:C)]组、高碘联合Poly(I:C)组,对照组和Poly(I:C)组自由饮用蒸馏水,高碘组和高碘联合Poly(I:C)组自由饮用0.05%NaI水,持续16周,Poly(I:C)组和高碘联合Poly(I:C)组第11周和第15周的周一、三、五每天腹腔注射一次1μg/μL Poly(I:C) 100μL。16周末取血清和甲状腺,分别利用ELISA法和病理学HE染色法验证EAT模型,TUNEL法和细胞色素C(Cyt-C)免疫组化法检测甲状腺滤泡细胞凋亡情况,real-time qPCR法检测Bcl-2家族成员在小鼠甲状腺中的mRNA表达水平。结果高碘饲养联合Poly(I:C)腹腔注射NOD-SCID小鼠建立了EAT模型;甲状腺滤泡上皮细胞凋亡程度和Cyt-C表达水平与炎症成正相关。高碘组和高碘联合Poly(I:C)组中Bcl-2家族促凋亡成员Noxa、PUMA、Bid的mRNA表达水平显著高于对照组和Poly(I:C)组(P<0.05)。结论线粒体细胞凋亡途径参与高碘诱发EAT的甲状腺细胞凋亡过程,细胞凋亡可能受到Bcl-2家族促凋亡成员Noxa、PUMA和Bid表达上调的调控。     

Effects of dietary trans-fatty acids on reproductive performance of Wistar rats

1. Wistar rats were fed for three successive generations on a semi-purified diet, in which the fat was provided by butter, sunflower oil, rapeseed oil or hydrogenated vegetable fat, differing in the content of cis,cis-18:2 and trans-18:1 fatty acids. Effects of these fats on the composition of adipose tissue and reproductive performance were studied. Fatty acids were analysed using high-performance liquid chromatography. 2. The fatty acid pattern of adipose tissue was closely related to dietary fat composition and, established in the first generation, did not change significantly in successive generations of rats. 3. Hydrogenated fat adversely affected litter size, sperm morphology and regularity of oestrous cycle, and prolonged the period of gestation in experimental animals. Differences observed between the generations were not significant. 4. Hydrogenated fat decreased the level of serum testosterone in males, but the differences observed in levels of serum progesterone in females were not apparently related to the dietary trans-fatty acids.     

Effect of a dietary fiber (beet fiber) on dimethylhydrazine-induced colon cancer in Wistar rats.

The modifying effect of a dietary fiber, Fibeta (beet fiber), on experimentally induced colorectal cancer was studied in Wistar rats. The rats were fed a powdered semisynthetic casein-based diet in which the carbohydrate pool was substituted with Fibeta as the sole source of fiber. Dimethylhydrazine dihydrochloride (DMH-2HCl) was used as initiator in a dose of 20 mg/kg body wt and given by gavage once a week for 10 weeks. Throughout the experiment the rats were offered the diets with different levels of fiber in a preinitiation period of 8 weeks, during the initiation, or in a 30-week postinitiation period. The study was terminated after one year. A protective effect of the fiber was not found at any stage of the colorectal carcinogenic process. Even though differences (not statistically significant) in tumor incidences were seen, these did not reflect any effect of the high or low fiber intake during the study. Analysis for volatile fatty acids in cecal content showed that continuous feeding with a fiber-rich diet resulted in significant increase in most of the volatile fatty acids. The relative change was highest for butyric acid. These findings do not support the hypothesis that butyric acid has a protective effect on colorectal cancer. The tumor yield in the present study was low compared with that reported in the literature, and possible causes for this are discussed.     

硒对实验性自身免疫性甲状腺炎大鼠甲状腺Fas/FasL表达的影响

目的 研究适碘条件下不同硒摄入水平对实验性自身免疫性甲状腺炎(EAT)大鼠甲状腺细胞凋亡蛋白Fas/FasL表达的影响.方法 将32只雌性Lewis大鼠按数字表法随机分成4组,分别设为对照组(C组),模型组(M组),补硒+模型组(Se++M组),低硒+模型组(Se-+M组),在适碘条件下(含10.90 mg/kg)对各组先施加不同水平的硒(Se++M组2 mg/kg,C与M组0.20 mg/kg,Se-+M组0.02 mg/kg)干预2周后,再采用猪甲状腺球蛋白免疫大鼠建立EAT模型,取甲状腺组织制成石蜡切片,采用免疫组织化学检测、比较Fas/FasL表达情况的差异.结果 EAT大鼠甲状腺Fas及FasL较对照均出现表达增加,其中Fas的表达有随补硒水平的升高而下降的趋势,Se++M组吸光度值(0.036±0.004)与M组(0.059±0.006)相比,Fas表达明显受到抑制(q=11.591,P=0.000),与Se-+M组(0.050±0.005)相比,Se++M组Fas呈较低表达水平(q=7.055,P=0.000);但补硒对FasL的表达无明显影响.结论 补硒能减少Fas在甲状腺细胞中的表达,对自身免疫性甲状腺疫病的发展具有抑制作用.     

The effect of selenium therapy on autoimmune thyroiditis

Selenium as an essential trace element is capable of exerting complex effects on the endocrine and immune system by its antioxidant capacity. The role of selenium is important because the level of free oxygen radicals is elevated in the physiological thyroid hormone synthesis. THE AIM OF STUDY: was to determine whether selenium therapy can influence the level of antithyroid peroxidase and antithyroglobulin antibodies or whether there is a correlation between antioxidant capacity and the titer of autoantibodies. METHOD: 132 patient with autoimmune thyroiditis were investigated in a prospective, blind and placebo-controlled study. L-thyroxine substitution therapy was made in both groups and the level of TSH remained in the normal range. The selenium-treated group (n = 70 patients, 68 female, mean age 41,4 +/- 9,5 year) was compared with the placebo-treated group (n = 62 patients, 61 female, mean age 42,7 +/- 8,3 year). Selenium therapy was continued by L-seleno-methionine (per os 2 x 100 microg/day) for one year. Determination of TSH, fT4, fT3 and autoantibodies was carried out by chemiluminescence method. Total antioxidant capacity was determined by Randox kit, the level of selenium in the sera by atomic absorption technique was measured. In the follow-up study, patients were controlled every third month and at the end of a one-year observation period. RESULTS: The level of selenium in the untreated patients was significantly lower than in treated patients and controls. The fT3/fT4 ration proved to be higher in patients after selenium therapy. The titer of antithyroid antibodies (mostly the antithyroid peroxidase) significantly decreased at the end of the study. An inverse correlation was found between antioxidant capacity and the level of antithyroid peroxidase antibodies. The volume of thyroid gland slightly diminished in treated patients. Side effects were not observed. CONCLUSIONS: Selenium completed with L-thyroxine is a suitable therapy for patients with autoimmune thyroiditis.     

Effect of dietary protamine on lipid metabolism in rats

Protamine has been widely used as a pharmaceutical product and natural food preservative. However, few studies have been conducted to assess the beneficial function of dietary protamine. This study examined the effects of dietary salmon protamine on serum and liver lipid levels and the expression levels of genes encoding proteins involved in lipid homeostasis in the liver of rats. Groups of male Wistar rats were fed AIN93G diet containing 2% or 5% protamine. After 4 weeks of feeding these diets, markedly decreased serum and liver cholesterol (CHOL) and triacylglycerol levels were noted. Increased activity of liver carnitine palmitoyltransferase-2 and acyl-CoA oxidase, which are key enzymes of fatty acid β-oxidation in the mitochondria and peroxisomes, was found in rats fed on protamine. Furthermore, rats fed protamine showed enhanced fecal excretion of CHOL and bile acid and increased liver mRNA expression levels of ATP-binding cassette (ABC) G5 and ABCG8, which form heterodimers and play a major role in the secretion of CHOL into bile. The decrease in triacylglycerol levels in protamine-fed rats was due to the enhancement of liver β-oxidation. Furthermore, rats fed protamine exhibited decreased CHOL levels through the suppression of CHOL and bile acid absorption and the enhancement of CHOL secretion into bile. These results suggest that dietary protamine has beneficial effects that may aid in the prevention of lifestyle-related diseases such as hyperlipidemia and atherosclerosis.     

氟对大鼠硒代谢的影响

为研究氟和硒的相互作用，按３×３析因实验设计，将氟和硒相配成９种实验饲料（氟水平为１、１５和６０ｍｇ／ｋｇ饲料，硒水平为０．０３、０．３和５．０ｍｇ／ｋｇ饲料），分别给予雄性Ｗｉｓｔａｒ大鼠，饲养１３周。结果显示：氟（６０ｍｇ／ｋｇ）虽对食用不同硒水平饲料大鼠体重增长和进食量无影响，但氟可缓解动物因硒中毒而引起全血谷胱甘肽含量和肛谷胱甘肽过氧化物酶活力下降，并且组织中有硒含量减少和毛硒含量增加的趋势。另一方面可见硒（５．０ｍｇ／ｋｇ饲料）能降低氟在骨骼中的积蓄。由此可认为氟和硒在体内存在拮抗作用。     

Effect of dietary homocysteine on copper status in rats

The effect on copper status of diets containing homocysteine, an intermediate in the transsulfuration pathway of methionine metabolism, was investigated in rats. Two groups of six male weanling Sprague-Dawley rats were provided with deionized water and pair-fed diets that were adequate (14.0 mg/kg) or deficient (1.3 mg/kg) in Cu to groups fed diets similarly adequate or deficient in Cu but containing DL-homocysteine (10 g/kg). Hemoglobin concentration, tissue Cu levels and the activities of the Cu-dependent enzymes--ceruloplasmin, superoxide dismutase and cytochrome c oxidase--were markedly lowered by Cu-deficient diets and by homocysteine. These dietary treatments also lowered the activity of glutathione peroxidase and produced concomitant increases in the activity of manganese-dependent superoxide dismutase and iron levels in the liver. However, dietary homocysteine decreased hepatic Mn and low Cu diets decreased cardiac iron content. Moreover, both dietary treatments significantly lowered kidney Fe levels. Homocysteine increased heart, liver and kidney weights (g/100 g body tissue) and greatly elevated the level of thiobarbituric acid reactive substances (TBARS) in heart tissue. These results indicate that dietary homocysteine can markedly lower Cu status in rats and result in tissue redistribution of Fe and increased cardiac levels of TBARS, a measure of lipid peroxidation.     

Hashimoto's thyroiditis, the model of organ-specific autoimmune disorders

Anti-thyroid antibodies were published first in this disease. Research of past fifty years provided evidence that the damage of thyrocytes was the result of a multistep process in which immunological, immunogenetic, epigenetic and environmental factors had been involved. It was clarified that the autoimmune thyroiditis was not identical with hypothyroidism since during this disease different functional stages were differentiated. Both the clinical picture and the immunological investigations have been proved to be important in the diagnosis. The author summarized the main principles for treatment and prevention of this disorder.     

Effect of sodium arsenite on reproductive organs of female Wistar rats

The present study was performed to investigate the subchronic effect of sodium arsenite on female Wistar rats. Mature female rats were divided into 4 groups of 12 animals each. Group I received distilled water, whereas the other 3 groups received sodium arsenite at 10, 30, and 50 µg/L doses for 60 days through drinking water. Half of the animals from each group were dissected after 30 days and the remaining after 60 days. A disruption in estrous cycle was observed with prolonged diestrous and metestrous phases. A significant increase in ovarian surface epithelium and follicular atresia was observed in treated rats (p ≤ .05). A significant decrease (p ≤ .05) in the uterine myometrium was observed. A significant increase (p ≤ .05) in the levels of lipid peroxidation along with decrease in the activities of antioxidant enzymes was observed. The results revealed that subchronic exposure of sodium arsenite causes degenerative changes in reproductive organs and induces oxidative stress in female rats.     

Effect of Aegle marmelos fruits on normal and streptozotocin-diabetic Wistar rats

The present study evaluates the antidiabetic effect of an aqueous extract of Aegle marmelos fruits (AMFEt) in diabetes. Female albino Wistar rats were randomly divided into five groups: normal (untreated), normal + AMFEt, streptozotocin (STZ)-treated, STZ-treated + AMFEt, and STZ-treated + glibenclamide. Rats were rendered diabetic by STZ (45 mg/kg) administered intraperitoneally. AMFEt (250 mg/kg) was given twice daily for 1 month. Blood glucose, plasma insulin, glycosylated hemoglobin, liver glycogen, and change in body weight were determined. Food intake and water intake were monitored daily. An oral glucose tolerance test was also performed to determine the effect of this extract. The results show that glucose level and glycosylated hemoglobin were increased and plasma insulin and liver glycogen were decreased in diabetic rats, and that treatment with AMFEt reversed the effects of diabetes on these biochemical parameters to near-normal levels.     

Effect of dietary fiber on hypercholesterolemia induced by dietary PCB or cholesterol in rats

Effects of 0.03% polychlorinated biphenyls (PCB) in the diet and various dietary fibers [konjac mannan (KM), pectin, sodium carboxymethyl cellulose (CMC) and cellulose] at a 5% level in the diet on serum and liver lipid metabolism and urinary ascorbic acid were studied. A comparison between dietary PCB and 1% cholesterol in the diet was also made. Serum albumin, protein, total and high density lipoprotein (HDL)-cholesterol, triglyceride, urinary and liver ascorbic acid, liver cholesterol and total lipids were increased in rats fed PCB. Pectin or KM depressed the elevation in serum protein, total and HDL-cholesterol, triglyceride and liver lipids due to PCB intake. Cellulose or CMC had no significant effect on these indices. Urinary ascorbic acid was not decreased by these dietary changes. Serum total cholesterol and low density lipoprotein (LDL) plus very low density lipoprotein (VLDL)-cholesterol, and liver total lipids, and cholesterol were significantly higher, and serum HDL-cholesterol and triglyceride were significantly lower in the cholesterol-fed group as compared to PCB-fed rats. Addition of KM to a cholesterol diet significantly depressed serum total cholesterol and LDL plus VLDL-cholesterol, liver cholesterol and total lipids. It seems likely that cholesterol metabolism is quite different during dietary PCB and cholesterol feeding.     

Effect of dietary restriction on liver protein synthesis in rats

At 6 wk of age, male Fischer F344 rats were fed a purified, casein-based diet either ad libitum or in the amount of 60% of the diet consumed by the rats fed ad libitum (restricted diet). Hepatocytes were isolated from the rats between 2.5 and 19 mo of age. The protein content of the hepatocytes isolated from the rats fed the restricted amount of diet was significantly lower than that of hepatocytes isolated from rats fed ad libitum. The DNA and RNA content of the hepatocytes were similar for the rats fed the two dietary regimens. The absolute rate of protein synthesis for hepatocytes isolated from rats fed ad libitum decreased 55% between 2.5 and 19 mo of age. However, the rate of protein synthesis by hepatocytes from rats fed the restricted amount of diet decreased only slightly with increasing age. At 19 mo of age, the rate of protein synthesis by hepatocytes from the rats fed the restricted amount of diet was significantly higher than the rate of protein synthesis for hepatocytes from rats fed ad libitum. Therefore, dietary restriction retards the age-related decline in liver protein synthesis.     

Effect of Wainan Rogo on body weight and plasma glucose in Wistar rats

Wainan Rogo (WR) is a deep-fat fried dough made from grated fresh cassava. It was found in a cross sectional case-control study to have a risk factor 3.2 times higher in diabetic than non diabetic indigenes of Borno State of Nigeria. This study examines the chemical composition, and effects of WR on body weight and blood glucose in Wistar rats. The study found a higher fat and lower protein composition of the WR diet, and found a higher plasma glucose in the WR fed rats and a more significant weight loss in this group than in the control (CF) fed rats. The findings of this study seem to support the high risk for diabetes associated with WR in the cross sectional study. The chemical composition of WR and its effect on body weight and blood glucose are further discussed, with a call for further studies of the food as a marker in the search for the pathophysiology of Malnutrition-Related Diabetes Mellitus (MRDM).