维生素A对免疫的影响

近年来发现,维生素A及其同类物对免疫功能具有一定影响,在抗感染和抗肿瘤的免疫方面有重要意义。一、维生素A影响免疫系统功能动物实验研究表明,维生素A缺乏的小鼠呈现胸腺和淋巴器官萎缩,胸腺淋巴细胞减少。喂去维生素A饲料的鸡,胸腺和法氏囊重量下降,鼻、副鼻窦和粘液束淋巴上皮组织中     

阿特拉津对BALB／c小鼠T淋巴细胞功能的影响

目的探讨阿特拉津对小鼠T淋巴细胞功能的影响。方法健康BALB／c小鼠按体重随机分为阿特拉津高剂量组（400mg／kg）、中剂量组（200mg／kg）、低剂量组（100mg／kg）和阴性对照组（蒸馏水）,经口灌胃,每天1次,连续21d。试验结束后,眼球取血,处死小鼠,观察胸腺组织病理学变化,采用MTY还原法和流式细胞仪分别检测脾脏T淋巴细胞增殖情况和胸腺T淋巴细胞亚群分布,酶联免疫吸附法检测血清中白细胞介素-2（interleu—kin-2,IL-2）和白细胞介素．4（interleukin-4,IL-4）含量。结果阿特拉津暴露使小鼠胸腺皮质细胞减少,各剂量组脾脏T淋巴细胞转化率低于阴性对照组（均有P〈0．05）。阿特拉津中、高剂量组胸腺CD3＋T淋巴细胞亚群比例以及CD4＋T／CD8＋T比值均低于阴性对照组（均有P〈0．05）,各剂量组CD4＋T淋巴细胞亚群比例均明显低于阴性对照组（均有P〈0．05）,CD8＋T淋巴亚群比例随染毒剂量增高有降低趋势,但差异无统计学意义（均有P〉0．05）。阿特拉津高剂量组血清IL-2和IL4含量明显降低（均有P〈0．05）。结论阿特拉津能抑制小鼠T淋巴细胞功能,因而有免疫毒性作用。     

脂肪酸合成酶抑制剂对Wistar大鼠免疫指标影响的研究

[目的]探讨脂肪酸合成酶抑制剂浅蓝菌素对wistar大鼠免疫指标的影响。[方法]腹腔注射浅蓝菌素，测定大鼠血清IL-2和INF-γ的变化及淋巴细胞转化率，在试验结束后测定胸腺和脾脏指数。[结果]与对照组和控制摄食组比较试验组IL-2水平显著升高（P〈0．05），INF-γ水平、脾脏指数和淋巴细胞转化率显著高于控制摄食组，胸腺指数高于对照组和控制摄食组。[结论]浅蓝菌素可明显改善机体的免疫机能。     

应用环孢菌素A制备小鼠免疫缺陷动物模型

目的探讨环孢菌素A制备免疫缺陷动物模型的方法与效果，为中医药防治艾滋病的实验研究提供合适的模型。方法小鼠腹腔注射环孢菌素A，注射量为25mg/kg·d，隔天一次，共3次。通过观察动物的一般症状和脾脏、胸腺、肺组织病理变化，并检测动物脾脏重量指数、胸腺重量指数、外周血CD4^＋、CD8^＋T细胞亚群百分率，综合评价免疫缺陷动物模型。结果与正常对照组比较，动物模型组出现反应迟钝，毛失光泽等一般症状，胸腺重量指数下降，CD4^＋T细胞百分率明显减少，CD8^＋T细胞百分率增高，胸腺组织萎缩、出现局部脂肪变性，肺脏有局灶性肺泡壁增厚、部分肺泡扩大。结论环孢菌素A可以成功诱导以CD4^＋T细胞减少为主要特征的免疫缺陷，可以建立符合HIV主要致病特点的动物模型。     

单纯性维生素A缺乏大鼠模型建立及相关指标观察

目的采用参照AIN-93G纯化饲料要求略加改良配制的维生素A缺乏饲料，建立维生素A缺乏大鼠模型，观察其营养状况及相关指标的变化。方法将雄性SD大鼠（n=16）随机分为正常对照组和维生素A缺乏组。实验至12周，测量血、肝脏维生素A含量及血常规、血生化和血中锌、铁、铜的含量。结果与正常组比较，维生素A缺乏大鼠的总摄食量、血清及肝脏维生素A含量、白细胞总数、血清锌、铜含量明显下降，血清AST、铁含量、锌铜比值显著升高。结论使用该维生素A缺乏动物饲料，可以成功建立维生素A缺乏动物模型，尤其对血中微量元素含量有一定的影响。     

氟对大鼠免疫器官的影响及“抗氟灵”对氟拮抗作用的研究

本文研究了对大鼠免疫器官的影响及“抗氟灵”对氟的拮抗作用。２４只大鼠被随机分成３组,Ａ组为阴性对照组,Ｂ组对染氟组,Ｃ组为氟加“抗氟灵”组,观察与检测了所有动物的胸腺及脾脏的蛋白质含量,脏器重量,脏器系数及形态学变化。结果显示;Ｂ组动物胸腺与脾脏的蛋白含量,脏器重量,脏器系数均明显下降,胸腺皮质明显变薄,淋巴细胞稀疏;Ｃ组动物的这些指标变化不明显。     

慢性应激对大鼠免疫功能损伤机制的实验研究

[目的]研究慢性应激对大鼠免疫功能的影响及其作用机制.[方法]通过建立慢性应激动物模型,免疫组织化学法检测脾脏T淋巴细胞亚群的阳性率,电镜观察脾脏超微结构的改变,黄嘌呤氧化酶法测定超氧化物歧化酶(SOD)活性,硫代巴比妥酸(TBA)法测定丙二醇(MDA)含量,彗星实验评价大鼠外周血淋巴细胞DNA损伤情况.[结果]与对照组相比,实验组大鼠脾脏超微结构异常明显,T淋巴细胞亚群比例异常,CD3 T细胞百分率、CD4 /CD8 值均下降(P＜0.05),CD8 T细胞百分率升高(P＜0.01),血清SOD活性(56.70±15.65)U/ml降低,MDA含量(9.21±2.75)nmol/ml升高(P＜0.05),彗星细胞发生率升高(P＜0.05).淋巴细胞DNA损伤与MDA含量呈正相关,SOD活性与CD3 T细胞、CD4 /CD8 比值呈正相关;MDA含量与细胞免疫功能下降水平呈正相关,淋巴细胞DNA损伤与细胞免疫功能下降水平呈正相关.[结论]慢性应激使大鼠血清MDA含量增加,SOD活性下降,脾脏超微结构改变,损伤外周血淋巴细胞DNA,从而影响机体的免疫功能.     

双酚A暴露对大鼠器官结构及细胞因子表达的影响

目的研究双酚A暴露对大鼠器官结构及细胞因子表达的影响。方法F344大鼠按体重随机分为对照组和低、中、高剂量组,分别给予0、4、40和400mg/kg双酚A,观察脾脏、胸腺、肝脏、肾脏组织形态学的改变,实时定量PCR测量脾脏IL-2、IL-12、IFN-γ、TNF-α和胸腺Fas、FasL六种细胞因子mRNA表达的改变。结果与对照组相比,高剂量组体重降低(P<0.05),脾脏白髓减少,脾小体缩小,肾小球缩小,肝脏出现肝细胞浑浊变性和纤维化,其它指标无明显改变。与对照组相比,各剂量组脾脏IL-2、IL-12、IFN-γ、TNF-α mRNA表达均显著降低(P<0.01),胸腺Fas表达下降(P<0.01),FasL表达在低剂量组出现一个短暂的下降后(P<0.05),在中、高剂量组明显上升(P<0.01)。结论双酚A,可改变靶器官的生长、发育及生理功能,影响细胞因子的表达,进而影响机体免疫功能。     

低剂量辐射对大鼠免疫功能影响的研究

目的本实验采用X射线全身照射Waister大鼠,观察低剂量照射诱导免疫适应性反应。方法通过流式细胞术检测低剂量照射后外周血NK细胞活性测定、CD4 、CD8 细胞的变化,通过免疫组化的方法来研究照射后细胞因子的变化。结果淋巴细胞亚群NK细胞活性测定、CD4 、CD8 细胞在100mGy照射后活性明显增强(P<0.05),而在500mGy照射后活性降低。100mGy照射后细胞因子IL-2、TNF-а的含量较其他组明显提高,胞浆着色成棕黄色。体重和脏器指数没有显著性变化。结论100mGy可增强大鼠免疫功能,增高淋巴细胞反应性,而500mGy可以抑制大鼠的免疫功能。     

维生素A强化食用油干预对少年儿童免疫功能的改善作用

目的:观察维生素A(VA)强化食用油营养干预对少年儿童免疫功能的改善作用。方法:在四个不同地区选择VA缺乏的小学生作为研究对象,用VA含量为7500μg/kg的食用油对受试儿童进行5个月营养干预,观察血清VA水平、免疫球蛋白(IgA,IgG,IgM)和补体C3含量的变化。结果:干预组儿童的血清VA水平明显高于对照组,血清IgA和补体C3含量得到显著改善,但IgG,IgM含量与对照组未见明显差别。结论:VA强化食用油可以有效改善儿童的VA营养状况,提高其免疫功能。     

Men with low vitamin A stores respond adequately to primary yellow fever and secondary tetanus toxoid vaccination

Current recommendations for vitamin A intake and liver stores (0.07 micromol/g) are based on maintaining normal vision. Higher levels may be required for maintaining normal immune function. The objective of this study was to assess the relationship between total body vitamin A stores in adult men and measures of adaptive immune function. We conducted an 8-wk residential study among 36 healthy Bangladeshi men with low vitamin A stores. Subjects received a standard diet and were randomized in a double-blind fashion to receive vitamin A (240 mg) or placebo during wk 2 and 3. Subjects received Yellow Fever Virus (YFV) and tetanus toxoid (TT) vaccines during wk 5. Vitamin A stores were estimated by isotopic dilution during wk 8. Vaccine-specific lymphocyte proliferation, cytokine production, and serum antibody responses were evaluated before and after vaccination. Vitamin A supplementation increased YFV- and TT-specific lymphocyte proliferation and YFV-specific interleukin (IL)-5, IL-10, and tumor necrosis factor-alpha production but inhibited development of a TT-specific IL-10 response. Both groups developed protective antibody responses to both vaccines. Some responses correlated positively with vitamin A stores. These findings indicate that the currently recommended vitamin A intake is sufficient to sustain a protective response to YFV and TT vaccination. However, YFV-specific lymphocyte proliferation, some cytokine responses, and neutralizing antibody were positively associated with liver vitamin A stores > 0.084 micromol/g. Such increases may enhance vaccine protection but raise the question of whether immune-mediated chronic diseases may by exacerbated by high-level dietary vitamin A.     

Effect of cholesterol feeding on tissue lipid perioxidation, glutathione peroxidase activity and liver microsomal functions in rats and guinea pigs.

The effect of cholesterol feeding on liver and aortic nonenzymatic lipid peroxidation and glutathione peroxidase activities, and on liver microsomal NADPH-dependent lipid peroxidation, codeine hydroxylation and cytochrome P-450 levels was examined in rats and guinea pigs. One percent cholesterol was added to a casein-sucrose-soybean oil basal diet for rats or a stock diet with 2% soybean oil for guinea pigs. The effect of vitamin E and cholestyramine was also examined in some experiments. Cholesterol feeding increased the rate of lipid peroxidation in liver and aortic homogenate both in rats and guinea pigs when fed non-vitamin E supplemented basal diets. Vitamin E supplementation prevented the increase in the aorta, but not as completely in the liver in rats, while the reverse was true in guinea pigs. The effect of cholestyramine was dependent on the level of vitamin E in the diet. Cholesterol feeding decreased glutathione peroxidase activities in rats and guinea pigs. In guinea pigs, cholesterol feeding also markedly decreased liver microsomal NADPH-dependent lipid peroxidation, codein hydroxylation and cytochrome P-450 levels especially when fed non-vitamin E supplemented basal diets. In rats, cholesterol feeding reduced liver microsomal NADPH-dependent lipid peroxidation and in some cases, increased microsomal codeine hydroxylation activities, but had no effect on microsomal cytochrome P-450 levels. Vitamin E supplementation increased liver and serum cholesterol levels in guinea pigs, but had no such effect in rats. Results of this study indicate that cholesterol feeding can result in various metabolic alterations in rats and guinea pigs. The implication of these alterations in atherogenesis requires further investigations.     

Vitamin A deficiency modifies lipid metabolism in rat liver

Liver fatty acid metabolism of male rats fed on a vitamin A-deficient diet for 3 months from 21 d of age was evaluated. Vitamin A restriction produced subclinical plasma and negligible liver retinol concentrations, compared with the control group receiving the same diet with 4000 IU vitamin A (8 mg retinol as retinyl palmitate)/kg diet. Vitamin A deficiency induced a hypolipidaemic effect by decreasing serum triacylglycerol, cholesterol and HDL-cholesterol levels. The decrease of liver total phospholipid was associated with low phosphatidylcholine synthesis observed by lower [14C]choline incorporation into phosphatidylcholine, compared with control. Also, liver fatty acid synthesis decreased, as was indicated by activity and mRNA expression of acetyl-CoA carboxylase (ACC), and incorporation of [14C]acetate into saponified lipids. A decrease of the PPARalpha mRNA expression was observed. Liver mitochondria of vitamin A-deficient rats showed a lower total phospholipid concentration coinciding with a decrease of the cardiolipin proportion, without changes in the other phospholipid fractions determined. The mitochondria fatty acid oxidation increased by 30 % of the control value and it was attributed to a high activity and mRNA expression of carnitine palmitoyltransferase-I (CPT-I). An increase in serum beta-hydroxybutyrate levels was observed in vitamin A-deficient rats. Vitamin A deficiency alters the mitochondria lipid composition and also enhances fatty acid oxidation by modifying the production of malonyl-CoA, the endogenous inhibitor of CPT-I, due to decreased activity of liver ACC. The incorporation of vitamin A into the diet of vitamin A-deficient rats reverted all the changes observed.     

Expression of retinoic acid nuclear receptors and tissue transglutaminase is altered in various tissues of rats fed a vitamin A-deficient diet.

The effects of vitamin A nutritional status on the levels of expression of retinoic acid nuclear receptors (RAR), and the retinoic acid-responsive gene, tissue transglutaminase, were determined in rats. Weanling male Sprague-Dawley rats fed a vitamin A-deficient diet for approximately 7 wk developed vitamin A deficiency, as confirmed by the depletion of liver retinol and retinyl palmitate. Controls were fed the same diet supplemented with 24 mg/kg retinyl acetate. The levels of expression of RAR beta mRNA were approximately 80% lower in bladder, brain, liver, lung and trachea and those of RAR gamma mRNA were approximately 50% lower in bladder, lung and trachea of rats fed the vitamin A-deficient diet than in controls. The levels of expression of RAR alpha mRNA were approximately 90% lower in brain and approximately 30% greater in liver, kidney, intestine and lung of rats fed the vitamin A-deficient diet. Vitamin A deficiency also resulted in reduced expression of tissue transglutaminase in the bladder, lungs and trachea, which paralleled the effects observed for RAR beta and RAR gamma. When vitamin A-deficient rats were subsequently fed a retinol-deficient diet supplemented with retinoic acid for 4 wk, the expression of RAR (beta and gamma) and tissue transglutaminase returned to the control levels. These results indicate that vitamin A nutritional status in rats influences the expression of both RAR and tissue transglutaminase in certain tissues.     

The effect of vitamin A deficiency on the in vitro cellular immune response of rats.

The effect of vitamin A deficiency on the response of splenic lymphocytes to mitogenic stimulation was determined in an experimental rat model. Male Lewis rats were divided into three groups. The ad libitum group (AL) was fed unlimited amounts of a vitamin A-supplemented diet. The vitamin A-deficient group (DEF) received a commercial vitamin A-free diet. The pair-fed group (PF) received a vitamin A-containing diet equivalent in amount to that consumed by the DEP group. During the early stages of vitamin A deficiency (determined by cessation of weight gain), the rats were killed and the isolated splenic lymphocytes subjected to mitogenic stimulation. Lymphocytes from DEF rats had one-third the transformation response to the mitogens Concanavalin A, Phytohemagglutinin and E. coli Lipopolysaccharide S of the AL and PF groups. When the DEF rats were supplemented with vitamin A, the transformation response returned to control values within 3 days. In addition to the alterations in the immune response, the DEF rats showed a marked leukopenia, a decrease in the number of circulating lymphocytes and an increase in the number of circulating neutrophils.     

Effects of vitamin A deficiency on mitochondrial function in rat liver and heart

The aim of this study was to investigate comparative effects of vitamin A deficiency on respiratory activity and structural integrity in liver and heart mitochondria. Male rats were fed a liquid control diet (control rats) or a liquid vitamin A-deficient diet (vitamin A-deficient rats) for 50 days. One group of vitamin-A deficient rats was refed a control diet for 15 days (vitamin A-recovered rats). To assess the respiratory function of mitochondria the contents of coenzyme Q (ubiquinone, CoQ), cytochrome c and the activities of the whole electron transport chain and of each of its respiratory complexes were evaluated. Chronic vitamin A deficiency promoted a significant increase in the endogenous coenzyme Q content in liver and heart mitochondria when compared with control values. Vitamin A deficiency induced a decrease in the activity of complex I (NADH-CoQ reductase) and complex II (succinate-CoQ reductase) and in the levels of complex I and cytochrome c in heart mitochondria. However, NADH and succinate oxidation rates were maintained at the control levels due to an increase in the CoQ content in accordance with the kinetic behaviour of CoQ as an homogeneous pool. On the contrary, the high CoQ content did not affect the electron-transfer rate in liver mitochondria, whose integrity was preserved from the deleterious effects of the vitamin A deficiency. Ultrastructural assessment of liver and heart showed that vitamin A deficiency did not induce appreciable alterations in the morphology of their mitochondria. After refeeding the control diet, serum retinol, liver and heart CoQ content and the activity of complex I and complex II in heart mitochondria returned to normality. However, the activities of both whole electron transfer chain and complex I in liver were increased over the control values. The interrelationships between physiological antioxidants in biological membranes and the beneficial effects of their administration in mitochondrial diseases are discussed.     

Low vitamin a intake affects milk iron level and iron transporters in rat mammary gland and liver

Marginal vitamin A deficiency is common and can result in a secondary iron (Fe) deficiency. A positive correlation between maternal Fe status and milk Fe was observed in lactating women supplemented with both vitamin A and Fe but not with Fe alone, suggesting effects of vitamin A on mammary gland Fe transport. We hypothesized that low vitamin A intake during lactation elicits differential effects on mammary gland and liver Fe transport and storage proteins, thus affecting milk Fe concentration but not maternal Fe status. We fed rats a control (CON, 4 RE/g) or a marginal vitamin A diet (AD, 0.4 RE/g) through midlactation. Effects on plasma, milk, liver and mammary gland Fe and vitamin A concentrations, and divalent metal transporter-1 (DMT1), ferroportin (FPN), ferritin (Ft), and transferrin receptor (TfR) expression were determined. Dams fed AD were not vitamin A or Fe deficient. Milk and liver vitamin A and Fe and mammary gland Fe concentrations were lower in rats fed AD compared with rats fed CON. Liver TfR expression was higher, whereas mammary gland TfR expression was lower in rats fed AD compared with rats fed CON. Liver Ft was unaffected, whereas mammary gland Ft was lower in rats fed AD compared with rats fed CON. Liver and mammary gland DMT1 and FPN protein levels were lower in rats fed AD compared with rats fed CON. Our results indicate that the mammary gland and liver respond differently to marginal vitamin A intake during lactation and that milk Fe is significantly decreased due to effects on mammary gland Fe transporters, putting the nursing offspring at risk for Fe deficiency.     

Vitamin A levels in regenerating rat liver. Effects on microsomal drug metabolism

After being maintained on a vitamin A-deficient or complete diet for a period of five weeks, male Sprague-Dawley rats were subjected to a two-thirds partial hepatectomy (PH) or sham operation. The vitamin A content of the liver of vitamin A-deficient, PH rats was below the limit of detection (less than 1 microgram/g liver). Rats fed the control diet and subjected to PH had hepatic levels of vitamin A that were 37% and 49% lower 48 and 72 hours after surgery, respectively, when compared with sham-operated controls. Hepatic microsomal cytochrome P-450 levels were significantly reduced in PH rats fed the complete diet 48 hours after PH and in PH rats fed either the deficient or complete diet 72 hours after. Vitamin A deficiency alone significantly reduced cytochrome P-450 levels. A combination of vitamin A deficiency and PH had the most dramatic effect on cytochrome P-450 and aminopyrine N-demethylase, which reduced the activity to approximately 50% of the activities found in the sham-operated control group. PH resulted in the greatest reduction in the rate of disappearance of benzo[a]pyrene in the presence of liver microsomes prepared from vitamin A-deficient rats.     

维生素A缺乏对大鼠脂质过氧化和抗氧化系统的影响

目的 :　研究维生素 A(VA)缺乏对 3w龄大鼠的脂质过氧化和抗氧化系统的影响。方法 :　健康 Wistar雄性大鼠 33只 ,按体重随机分为 A(VA完全缺乏组 ) ,B(VA轻度缺乏组 ) ,C(VA正常对照组 )三组。每组 1 1只 ,实验期为 84d。观察指标有 :血清 VA,血清、肝脏及脑组织的超氧物岐化酶 (SOD)活性 ,全血、肝脏及脑组织的谷胱甘肽过氧化物酶 (GSH- Px)活性 ,血清、肝脏及脑组织的丙二醛 (MDA)含量 ,并采用电子自旋共振 (electron spin resonance,ESR)和自旋捕捉技术直接测定大鼠肝组织中的氧自由基。结果 :　 A、B组大鼠血清、肝脏及脑组织 SOD活性明显下降 ,全血、肝脏及脑组织 GSH- Px活性明显降低 ,血清、肝脏及脑组织 MDA含量显著升高 ,ESR图谱出现了 N- H偶合的三组双峰波。结论 :　 VA完全或轻度缺乏均可以使大鼠脂质过氧化反应明显增强 ,而抗氧化能力明显减弱     

Exposure to the carcinogen benzopyrene depletes tissue vitamin A: beta-carotene prevents depletion

Evidence in humans and laboratory animals supports a cancer-protective effect of vitamin A, but the mechanism remains unclear. While vitamin A deficiency causes squamous metaplasia, and lung cancer patients have lower vitamin A status, their serum vitamin A levels are not indicative of deficiency. We hypothesize that local enzymatic degradation of vitamin A can be induced by exposure to carcinogens such as benzopyrene found in cigarette smoke. This study was designed to determine if benzopyrene exposure depletes tissue vitamin A and whether beta-carotene might prevent the depletion. Weanling male Fischer rats were fed a nutritionally complete purified diet, supplemented with or without benzopyrene at 400 mg/kg feed or beta-carotene at 2 g/kg feed. Vitamin A content of the liver, small intestine, and serum was determined by high-performance liquid chromatography. There was no effect of benzopyrene feeding on serum retinol levels through four weeks. However, there was a decline in tissue retinol in the liver and small intestine by two weeks, with a 30% decline by four weeks (p less than 0.05). In rats fed beta-carotene, there was no effect of benzopyrene on tissue vitamin A level. These results indicate that exposure to benzopyrene induces a local tissue vitamin A depletion despite a vitamin A-sufficient diet and maintenance of serum vitamin A levels. A high intake of beta-carotene prevented the vitamin A depletion effect of benzopyrene exposure. Further studies appear warranted to determine whether some of the adverse effects of environmental carcinogens, as found in cigarette smoke, charcoal-broiled meats, and industrial wastes, might be alleviated by dietary intervention.