基础营养

含金属硫蛋白蛋奶粉对小鼠肝细胞实体瘤的治疗作用;乳凝集素对新生仔兔小肠粘膜及小肠CD4^＋,CD8^＋,CD25^＋淋巴细胞发育的影响;大豆异黄酮联合叶酸对胎鼠脑细胞Pax3和Cx43表达的影响;大豆异黄酮对大鼠肾脏局部辐射的防护作用;转金属硫蛋白基因平菇对小鼠辐射后抗氧化能力的影响     

重金属在金属硫蛋白基因表达中的调控作用

重金属具有诱导金属硫蛋白基因转录的能力,重金属的储存、运输、代谢及解毒与金属硫蛋白密切相关,研究其对金属硫蛋白基因的调控作用显得至关重要。本文对金属硫蛋白的基因结构、金属调控体系作了较详细的阐述,对重金属元素对其的调控作用及其对机体的影响等进行了综述。     

镉对Ⅱ型糖尿病小鼠金属硫蛋白基因表达的诱导与镉肾脏毒性之关系

目的 探讨金属硫蛋白基因诱导表达能力与Ⅱ型糖尿病小鼠（ob/ob小鼠）对镉金属硫蛋白肾脏毒性易感性之间的关系。方法 以β-actin为内参照,采用半定量RT－PCR方法检测在相同肾皮质镉水平条件下,镉对ob/ob小鼠和瘦型小鼠（正常小鼠）肾皮质MT1和MT2基因的诱导表达。结果 镉对ob/ob小鼠肾皮质MT1和MT2基因诱导表达的能力过低,而镉对瘦型小鼠MT1及MT2基因具有明显的诱导能力。结论 本研究提示Ⅱ型糖尿病小鼠对镉肾脏毒性易感的可能原因与糖尿病小鼠肾中镉对MT基因的诱导能力过低有关。     

大豆异黄酮对辐射小鼠免疫功能的防护作用

目的 研究大豆异黄酮(SI)对辐射小鼠免疫功能的防护作用,为SI抗辐射功能食品的开发提供参考.方法 96只雄性昆明小鼠,随机分为正常对照组、辐射对照组和实验组(补充0.5％SI),喂养2周后,后2组给与一次性的4Gy137CS辐射.辐射后24h和3d分批进行小鼠吞噬功能、耳廓肿胀率、血清溶血素值和免疫球蛋白水平检测....     

小鼠肾脏中金属硫蛋白基因诱导表达的时程变化

目的 探讨重复性注射CdMT诱导小鼠肾脏MT基因表达的时程变化。方法 采用RT-PCR方法半定量检测重复性短时间间隔皮下注射镉金属硫蛋白（CdMT)染毒后小鼠肾皮质金属硫蛋白（MT1、MT2）基因表达的时程变化。结果 自CdMT染毒后12h。与对照组相比肾皮质MT1基因表达有增强的趋势，染毒后12h及24h，肾皮质MT2基因表达明显增强，其表达高峰均出现在CdMT染毒后24h，至168hMT1gn MT2基因表达均恢复到基准水平，结论 重复性短时间间隔皮下注射CdMT能够诱导小鼠肾皮质MT1及MT2基因的表达，并且MT1及MT2基因表达的时程变化基本一致。     

金属硫蛋白的分子生物学研究进展

本文对金属硫蛋白的基因结构、表达调控及染色体定位做了较详细的阐述，对当前有关金属硫蛋白的分子生物学新技术和新进展包括金属硫蛋白增强子运用，锌敏感蛋白的纯化及功能、缺如金属硫蛋白基因表达小鼠的建立和应用等做了综述，并对金属硫蛋白家族新成员－－生长抑制因子做了简单介绍。     

大豆异黄酮对电离辐射小鼠抗氧化功能的影响

目的研究大豆异黄酮对电离辐射后抗氧化能力的影响 ,为研制防治辐射的功能食品提供理论依据。方法 30只雄性昆明小鼠 ,随机分为正常对照组、辐射对照组和补充 0 .5 %的大豆异黄酮组 ,喂养 2周后 ,后 2组以 4 .0Gyγ射线照射 ;于照射后 1周和 2周取血 ,2周杀死小鼠取脾脏、胸腺和肝脏 ,观察血和组织的抗氧化指标变化。结果辐射使小鼠血清和胸腺、肝脏的MDA水平明显升高 ,SOD和GSH -Px活力明显下降 (P <0 .0 5 )。补充大豆异黄酮 2周后 ,使血清、肝脏和胸腺MDA水平较辐射对照组分别降低 2 0 .7%、2 3.5 %和 2 4 .9% ,使血清、肝脏和胸腺SOD活性较辐射对照组分别提高 18.4 %、13.3%和 8.2 % ,使血清、肝脏和胸腺GSH -Px活力较辐射对照组分别提高 12 .6 %、13.6 %和 2 0 .5 % ,变化均具有统计学意义。结论膳食中补充 0 .5 %大豆异黄酮可明显提高电离辐射机体的抗氧化能力 ,进而提高机体抗辐射能力。     

金属硫蛋白对镍致小鼠肝损伤的保护作用

目的探讨金属硫蛋白对镍致小鼠肝损伤的保护作用及其机制。方法利用硫酸镍染毒复制小鼠肝损伤的模型,然后腹腔注射不同剂量的金属硫蛋白7 d,检测肝脏器系数、肝功能及肝组织脂质过氧化等指标,并行肝组织病理学观察。结果肝损伤模型组与金属硫蛋白(MT)保护组小鼠肝脏器系数差异有统计学意义(P<0.05),随着MT剂量的增加,肝脏器系数逐渐降低(P<0.05);MT保护组肝细胞炎性浸润、水肿及坏死明显减轻,肝窦结构有恢复;MT保护组小鼠血清AST、ALT、GGT及总胆汁酸均低于损伤模型组(P<0.05),肝组织MDA、GSH低于损伤模型组(P<0.05),而SOD、GSH-Px活性则高于损伤模型组(P<0.05),并均有较强的剂量依赖关系。结论金属硫蛋白对镍致小鼠肝损伤有保护作用,保护机制可能与减轻氧化损伤有关。     

火麻仁蛋白对小鼠抗疲劳和免疫调节功能的初步研究

目的研究火麻仁蛋白对小鼠抗疲劳和免疫调节的作用。方法通过游泳时间、血乳酸和血清尿素氮测定观察小鼠的抗疲劳能力,应用免疫器官相对重量称重、细胞和体液免疫功能测定、以及脾脏T淋巴细胞亚群分类实验研究小鼠的相关免疫学指标。结果火麻仁蛋白能明显延长小鼠游泳时间、降低血乳酸值、增加肝糖原含量;并且火麻仁蛋白明显增强小鼠ConA诱导的脾淋巴细胞转化和迟发型变态反应,提高小鼠抗体生成数和半数溶血值,增强小鼠巨嗜细胞吞噬能力,增加小鼠外周血液中T淋巴细胞百分比。结论火麻仁蛋白可能增强小鼠抗疲劳能力和可增强小鼠免疫调节作用。     

戊型肝炎病毒嵌合蛋白的免疫应答的初步研究

目的：对含有HEV主要抗原表位的嵌合蛋白进行表达与纯化，并对其免疫原性进行研究。方法：将含有一段HEV ORF2基因片段（394-660aa）和HEVORF3全基因的表达质粒pHEV23在大肠杆菌中进行异丙基硫代半乳糖苷（IPTG）诱导表达，其表达产物经Ni^2＋-NTA树脂亲和纯化，透析复性。纯化蛋白免疫小鼠，用ELISA检测小鼠血清IgG抗体，T细胞增殖反应检测细胞免疫应答。以Western-blot检测纯化蛋白对患者阳性血清的免疫反应性。结果：纯化蛋白的分子量为55KDa，纯度达90％以上；实验组特异性抗体水平明显高于对照组；T细胞增殖反应实验组与对照组比较有极显著性差异。纯化蛋白能与患者阳性血清呈特异反应。结论：嵌合蛋白具有良好的免疫原性和免疫反应性，为进一步研究开发HEV诊断试剂盒及基因工程疫苗提供了基础。     

The cholesterolaemic effects of dietary fats in cholesteryl ester transfer protein transgenic mice.

In order to investigate the role of cholesteryl ester transfer protein (CETP) in the cholesterolaemic response to dietary fats, we analysed plasma lipid profiles of CETP-transgenic and control C57BL/6 mice fed standard chow (AIN-93G; AIN), a low-fat diet, and diets high in butter (saturated fatty acids; SFA), high-oleic acid safflower oil (monounsaturated fatty acids; MUFA), and safflower oil (polyunsaturated fatty acids; PUFA) for 5 weeks. Each group contained four or five mice. There were significant diet and dietxgenotype effects on plasma total cholesterol (TC; and respectively), liver TC ( and respectively), and esterified cholesterol (EC; and respectively); diet effects on plasma triacylglycerol liver free cholesterol and body weight a genotype effect on body-weight gain and a dietxgenotype effect on energy intake In transgenic mice the SFA diet caused significantly higher plasma TC than the PUFA diet In control mice MUFA and PUFA diets, but not the SFA diet, caused significantly higher plasma TC than the low-fat and AIN diets Transgenic mice fed PUFA had lower plasma TC while transgenic mice fed MUFA had lower LDL+VLDL-cholesterol than controls in the same dietary groups. Transgenic mice fed MUFA and PUFA diets also had significantly higher liver TC and respectively) and EC and respectively) than controls fed the same diets. In the present study we showed that: (1) CETP transgenic mice had a cholesterolaemic response to dietary fats similar to that in human subjects; (2) CETP transgenic mice fed PUFA showed significantly lower plasma TC, while those fed MUFA had lower LDL+VLDL-cholesterol than controls; (3) hepatic accumulation of cholesterol, possibly resulting from the combination of the enhanced cholesteryl ester transfer to apolipoprotein B-containing lipoproteins and increased hepatic uptake of cholesterol, may contribute to the cholesterol-lowering effect of MUFA and PUFA in CETP-transgenic mice; (4) CETP may play a role in appetite and/or energy regulation.     

Effect of moderate caloric restriction and/or weight cycling on mammary tumor incidence and latency in MMTV-Neu female mice

Recently, we reported that intermittent caloric restriction-refeeding reduces mammary tumor (MT) incidence and extends latency in murine mammary tumor virus (MMTV)-transforming growth factor (TGF)-a mice to a greater extent than does chronic caloric restriction. Here, this same weight-cycling protocol was applied to MMTV-Neu female mice, which develop MTs at a much younger age than do TGF-a mice. This study consisted of three experimental groups: mice fed an AIN-93M diet ad libitum, mice intermittently fed an AIN-93 modified diet (2-fold increase in protein, fat, vitamins, and minerals) at 50% of the amount fed to the ad libitum-fed mice for 3-wk intervals and then fed an AIN-93M diet ad libitum for 3-wk intervals, and mice chronically restricted, pair fed to the intermittently restricted mice by feeding 2:1 mixtures of AIN-93M-AIN-93 modified diets for each 6-wk feeding interval. Mice were euthanized when MTs reached a length of 20 mm or at 80 wk of age. Cumulative caloric intake was 10% lower (not significant) for intermittently restricted mice and 16% lower (P < 0.05) for chronically restricted mice than for ad libitum-fed mice. Final body weights were significantly different as follows: ad libitum-fed > intermittently restricted > chronically restricted. Fat pad weights were greater in ad libitum-fed than in intermittently restricted and chronically restricted mice. MT incidence of ad libitum-fed mice was 37% compared with 22% for intermittently restricted mice and 33% for chronically restricted mice (not significant). There were no differences in MT weight or number among the groups. These results indicate that intermittent caloric restriction-refeeding provides a moderate protective effect, whereas chronic caloric restriction provides no significant protection against MT development in transgenic Neu mice.     

转基因大米的免疫毒理学评价

目的　评价转基因大米和非转基因大米对小鼠免疫功能的异同。方法　以转豇豆胰蛋白酶抑制剂 (cowpeatrypsininhibitor ,CpTI)基因大米和母系非转基因大米喂养BALB C小鼠 30天 (均配成AIN 93G的全价营养饲料 ,并且含有最大量的转基因大米或非转基因大米 ) ,比较各组小鼠的各项免疫毒理指标 :体重、脏器指数、血常规、淋巴细胞分类、血清抗体滴度、空斑试验 (PFC)、迟发型皮肤过敏反应 (DTH)、腹腔巨噬细胞吞噬鸡红细胞试验。结果　发现转基因大米和非转基因大米喂养的小鼠各项免疫毒理指标无差异。结论　转基因大米对小鼠的免疫功能的影响与非转基因大米基本相同 ,转基因大米与非转基因大米在免疫毒理学方面的评价具有“实质等同性”。     

金属硫蛋白抗辐射的实验研究

目的 :　研究口服金属硫蛋白 (metallothionein,MT)对机体抵御电离辐射能力的影响。方法 :　采用灌胃方式给予受试小鼠 MT,连续灌胃 30 d后分别接受 7Gy、8Gy60 Co-γ一次性辐照及每周一次 1 Gy小剂量连续 8次辐照。于照后不同时间取血测定各组小鼠白细胞和淋巴细胞 ,并记录 8Gy一次性辐照后小鼠存活时间。结果 :　 (1 ) 7Gy辐照的实验条件对于抗辐射保健食品功能的观察较为适宜。 7Gy辐照后淋巴细胞的下降趋势与白细胞基本一致 ,淋巴细胞可以作为评价抗辐射保健食品实验的一项观测指标。 (2 )灌胃 MT0 .6mg/kg bw和 3mg/kg bw30 d的小鼠经 7Gy一次辐照后 ,白细胞和淋巴细胞数量明显高于未服 MT的辐照对照组。 (3)经 8Gy照射后服用 MT的小鼠比辐照对照组小鼠平均存活时间提高了 72 % (P<0 .0 5)。 (4)每周一次 1 Gy小剂量60 Co-γ射线照射小鼠 ,7次 (累计剂量 7Gy)和 8次 (累计剂量 8Gy)照射之后 ,服用 MT的小鼠白细胞和淋巴细胞数量明显高于未服 MT的辐照对照组小鼠。结论 :　口服 MT能够延长一次性大剂量电离辐射小鼠的存活时间 ,降低一次性大剂量和多次小剂量电离辐射对免疫系统的损伤     

Low-dose exposure and immunogenicity of transgenic maize expressing the Escherichia coli heat-labile toxin B subunit

BACKGROUND: Transgenic maize, which produces the nontoxic B subunit of the Escherichia coli heat-labile toxin (LT-B) in seed, has proven to be an effective oral immunogen in mice. Currently, there is considerable concern over accidental consumption of transgenic maize expressing LT-B by humans and domestic animals. We have yet to define nonimmunogenic levels of transgenic LT-B when ingested. OBJECTIVES: Our goal in this study was to determine the highest dose of LT-B orally administered in mice that does not result in a measurable immune response. We defined an immune response as specific serum or mucosal IgG or IgA significantly greater than background after three feedings (0.0002-20 mug) or a priming response induced by the intermittent feeding. METHODS: We fed transgenic maize pellets on days 0, 7, 21, and 49 and collected serum and fecal samples weekly. Serum was analyzed for LT-B-specific IgG and IgA, and feces was analyzed for LT-B-specific IgA. RESULTS: We observed a dose-dependent anti-LT-B antibody response with high specific antibody concentrations in groups fed high doses (0.2, 2, 20 mug) of LT-B maize. Mice fed 0.02 mug LT-B demonstrated immune priming in 62.5% of the animals. Mice that were fed 相似文献   

Analysis of the effects of overexpression of metallothionein-I in transgenic mice on the reproductive toxicology of cadmium.

Exposure to low levels of cadmium reduces fertility. In male mice spermatogenesis is highly sensitive to cadmium, whereas in females the peri-implantation period of pregnancy is sensitive. To examine the potential roles of the cadmium-binding protein, metallothionein (MT), in the reproductive toxicology of cadmium, we examined a transgenic mouse strain that overexpresses metallothionein-I (MT-I). These mice had dramatically increased steady-state levels of MT-I mRNA and MT in the testes and in the female reproductive tract during the peri-implantation period of pregnancy, and this overexpression occurred in a cell-specific and temporally regulated manner similar to that of the endogenous MT-I gene. Transgenic and control males were injected with cadmium, and the histology of the testes was examined. An injection of 7.5 mumol Cd/kg had no effect on histology of the testes in either transgenic or control mice. In contrast, an injection of 10 mumol Cd/kg caused rapid changes in the histology of the testes and resulted in pronounced testicular necrosis in both control and transgenic mice. Female transgenic and control mice were mated and then injected with cadmium (30-45 mumol Cd/kg) on the day of blastocyst implantation (day 4). In both of these groups, injection of cadmium reduced pregnancy rate, and no dramatic protection was afforded by maternal and/or embryonic overexpression of MT. Thus, overexpression of MT-I does not significantly protect against either of these cadmium-induced effects on fertility.     

Resveratrol From Transgenic Alfalfa for Prevention of Aberrant Crypt Foci in Mice

Transgenic alfalfa (Medicago sativa L.), which accumulated resveratrol-glucoside (RG), was incorporated into diets and fed to female, 6-wk-old CF-1 mice for 5 wk. Mice fed diets containing transgenic alfalfa with supplemented α -galactosidase had significantly fewer azoxymethane (AOM)-induced aberrant crypt foci (ACF) in their colon relative to mice fed the transgenic alfalfa diets without added α -galactosidase (P = 0.02). Resveratrol-aglycone (Rag) was detected in the colon of 100% of mice fed transgenic alfalfa diets with supplemented α -galactosidase and in 60% of mice fed transgenic alfalfa without α -galactosidase (P < 0.05). Colonic concentrations of Rag (< 0.5 nmol/g tissue) in mice fed transgenic alfalfa with α -galactosidase (0.22 ± 0.18 nmol/g tissue) tended to be higher than in animals fed diets without α -galactosidase (0.1 ± 0.08 nmol/g tissue; P = 0.09). The use of N-(Bn-butyl)-deoxygalactonojirimycin, an inhibitor of lactase-phlorizin hydrolase (LPH), in transport studies with everted jejunal sacs from CF-1 mice (N = 8) suggested that LPH is involved in the intestinal deglycosylation of RG. Our collective findings suggest that RG from transgenic alfalfa is metabolized and absorbed in the upper intestine and does not reach the colon in sufficient amounts to inhibit ACF.     

Metallothionein in mice reduces intestinal zinc loss during acute endotoxin inflammation, but not during starvation or dietary zinc restriction

Normal metallothionein [(MT)+/+] and MT-null (MT-/-) mice were used to examine the influence of MT on Zn retention and the metabolic consequences of 2 d food deprivation, with and without inflammation induced by intraperitoneal injection of bacterial endotoxin lipopolysaccharide (LPS). LPS reduced fecal Zn concentration in MT+/+ mice from 5.9 +/- 0.2 micromol/g on d 1 to 2.2 +/- 0.2 micromol/g on d 2, but not in MT-/- mice, 5.9 +/- 0.2 and 5.7 +/- 0. 5 micromol/g, respectively. MT+/+ mice fed an 8 mg Zn/kg diet and injected with LPS excreted 40% less Zn over 2 d than their MT-/- counterparts. Starvation for 2 d did not lower fecal Zn concentration in either genotype, although in MT+/+ mice, urinary Zn excretion was reduced from 12.7 +/- 1.3 nmol on d 1 to 5.9 +/- 1.8 nmol on d 2 and plasma Zn concentration was lowered to 9.8 +/- 0.4 micromol/L. Zn was not reduced in urine or plasma of MT-/- mice, with respective values of 10.8 +/- 2.0 nmol on d 1, 9.3 +/- 2.9 nmol on d 2 and 13.0 +/- 1.0 micromol/L. LPS injection resulted in much higher total liver Zn (677 +/- 27 nmol) and MT (106 +/- 2 nmol Cd bound/g) than starvation (Zn = 405 +/- 21, MT = 9 +/- 3) in MT+/+ mice after 2 d, but did not further reduce urinary Zn. LPS-injected MT-/- mice had no rise in liver Zn or fall in plasma and urine Zn. MT-/- mice fed a Zn-deficient (0.8 mg Zn/kg) diet lost 10% of body weight over 25 d compared with no loss in MT+/+ mice. Despite this, MT-/- mice excreted no more Zn via the gut than did MT+/+ mice. In summary, MT inhibits intestinal Zn loss when highly expressed. When uninduced, typically during Zn deficiency, MT appears to conserve Zn and body mass by reducing only urinary and other nonintestinal Zn losses.     

Zn-depleted mice absorb more of an intragastric Zn solution by a metallothionein-enhanced process than do Zn-replete mice

The influence of metallothionein (MT)(2) on Zn absorption was investigated in MT-null (MT-/-) and normal (MT+/+) mice fed Zn-depleted (ZnD) diets for 7 d and compared with those fed Zn-replete (ZnR) diets in a previous study. Mice were starved for 20 h, then administered an oral gavage of aqueous (65)ZnSO(4) solution at doses of 154, 770 or 1540 nmol of Zn, and the amount transferred into nongut tissues was determined 4 h later. (65)Zn transfer did not differ between genotypes in ZnR mice. However ZnD MT+/+ mice had a 30-40% greater transfer from the 154 and 770 Zn doses compared to ZnR MT+/+ mice. This was not observed in MT-/- mice. In MT+/+ mice, Zn depletion enhanced the induction of MT by Zn in the intestine and pancreas. (65)Zn uptakes in the liver and pancreas were greater in MT+/+ than MT-/- mice, and this was greater (50%) at the 154 and 770 doses in mice fed ZnD diets. Plasma Zn concentrations were raised to a similar extent in ZnR and ZnD MT-/- mice. ZnR MT+/+ mice had significantly lower plasma Zn levels than MT-/-mice; this difference was less marked in the ZnD mice. We conclude that a MT-facilitated enhancement in Zn absorption occurs in response to dietary Zn deficiency.