缺锌及补锌对大鼠体内元素分布和血脂的影响

为了解锌缺乏及补锌对大鼠体内元素分布和血脂的影响。将出生后断乳一周的SD大鼠随机分为缺锌组、配喂组、对照组、补锌组和高锌组五组,缺锌组、对照组和高锌组分别用缺锌饲料(锌含量<1mg/kg)、常锌饲料(锌含量为50 mg/kg)和高锌饲料(锌含量为150mg/kg)喂养8周,补锌组用缺锌饲料喂养三周后改用高锌饲料喂养五周,配喂组用常锌饲料喂养,给料量按缺锌组前一天实际进食量添加。8周后处死,用极谱法测定血清中锌、铜、铁和钙的含量,用原子吸收分光光度法测定肝、肾、脾和睾丸中锌、铜、铁和钙的含量,用酶法测定血清中血脂的含量。结果发现,缺锌使大鼠血清、肝脏、脾脏、肾和睾丸中锌和铁的含量显著降低,肾、脾脏中铜的含量下降,缺锌大鼠体内血清中甘油三酯、胆固醇、高密度脂蛋白和低密度脂蛋白的含量未见下降。说明锌缺乏不仅直接导致组织器官中锌含量降低,而且对其他元素在体内的代谢与分布产生影响。缺锌对大鼠体内血脂的影响不明显。     

缺锌对衰老小鼠抗氧化系统和肝脏DNA损伤修复功能的影响

目的　通过D 半乳糖诱导小鼠衰老模型 ,探讨缺锌对衰老小鼠抗氧化系统和肝脏DNA损伤与修复的影响。　方法　雄性 3月龄小鼠 70只 ,随机分成 5组 :青年组、衰老模型组、衰老缺锌组、衰老配喂组和衰老补锌组。各衰老组按 10 0mg /kg经颈背部皮下给予D 半乳糖注射液 ,青年组给予等剂量的生理盐水 ,连续 30d。衰老缺锌组和补锌组喂饲缺锌饲料 (含锌 1 6 1μg/kg) ,其他组喂饲正常锌饲料 (含锌 5 0 μg/kg) ,最后 2周补锌组喂饲补锌饲料 (10 0 μg/kg)。第 30天处死小鼠 ,取样检测血清锌、肝锌、超氧化物歧化酶、丙二醇、肝脂褐质和DNA损伤情况。　结果　与衰老模型组相比 ,衰老缺锌组血清锌 (0 5 3± 0 1)mg/L、肝锌 (14 5 4± 2 18)mg/L水平下降 ,血清和肝超氧化物歧化酶活性〔(14 2 87± 10 16 )NU/ml和 (180 11± 13 2 2 )NU/ml,P <0 0 5〕降低 ,丙二醇含量升高 ,肝脂褐质含量增高 ;彗星试验显示衰老缺锌组小鼠肝DNA损伤加重 ,彗星细胞尾长 /总长比值显著增加。补锌后上述指标均有改善。　结论　锌可有效的影响衰老的速度和程度 ,缺锌可加速衰老的进程 ,适当补锌有助于延缓衰老。     

补锌对衰老大鼠睾丸细胞凋亡和一氧化氮合酶的影响

探讨补锌对衰老过程睾丸细胞凋亡的影响及其可能机制。方法选用２４月龄Ｗｉｓｔａｒ雄性大鼠１６只,均分为实验组和对照组,实验组和对照组分别喂养补锌和常锌饲料,喂养４ｗ后,采用原子吸分光光度法测定血清锌含量;采用放射免疫分析法测定血清睾丸酮酮含量;采用ＮＡＤＰＨ－ｄ组织化学法显示睾丸细胞一氧化氮合酶活性;采用原位缺口平移技术显示睾丸凋亡细胞数目。结果与对照组相比,老年大鼠补锌４ｗ后,血清锌含量明显升高;     

中药治疗对血吸虫肝纤维化鼠血清微量元素的影响

将30只大鼠随机分为3组,正常对照组、感染组及治疗组.感染组及治疗组大鼠经腹部感染尾蚴100尾,感染第7周,以吡喹酮杀虫治疗,第8周开始治疗组给予中药制剂灌胃治疗.对比各组微量元素锌、铜、钙、镁、铁含量.发现与对照组比较,感染组鼠血清锌、铁、钙含量明显降低,铜含量明显升高;治疗组鼠各血清微量元素含量随着用药时间延长逐渐恢复正常.提示中药制剂对血吸虫肝纤维化有较好的治疗作用.     

新生期大鼠接种极低密度脂蛋白对部分免疫学及生物化学指标的影响

目的 探讨新生期大鼠接种极低密度脂蛋白是否能产生免疫耐受,以及接种后对血脂和内皮素水平的影响.方法选取体重在150～180 g雄性Wistar大鼠40只,制作高脂模型后取血,梯度密度离心提取极低密度脂蛋白并测定其蛋白含量.将出生4 h内的Wistar雄性乳鼠按窝别随机分为两组,极低密度脂蛋白组腹腔注射极低密度脂蛋白0.3 mg,对照组注射等体积生理盐水,普通饲料喂养3周.从两组大鼠中各随机抽取10只腹腔注射极低密度脂蛋白,喂养15天后取血测血清抗极低密度脂蛋白水平;剩余大鼠高脂饲料喂养60天,取血测血脂、内皮素及T细胞增殖水平.结果与对照组相比,极低密度脂蛋白组抗体水平降低(P<0.05),T细胞增殖水平有所下降(P<0.05),而血脂及内皮素水平变化不明显.结论 新生期大鼠接种极低密度脂蛋白可以诱导免疫耐受.     

微量元素与冠心病及其血脂的关系探讨

目的探讨微量元素与冠心病及其高血脂的关系.方法 用电感耦合等离子体原子发射光谱法测定了82例冠心病患者的6种微量元素变化,并与血脂做相关分析.结果示血清铁、锌、锌、铜比和铅在冠心病组较正常组明显增高,铬明显降低(P<0.01或0.001),铜和镉两组间无统计学差异.总胆固醇和低密度脂蛋白胆固醇分别与铁、锌、铅呈显著正相关,与铬呈显著负相关,高密度脂蛋白胆固醇与锌呈显著负相关(P<0.05或0.01).结论 提示部分微量元素的不平衡可能影响脂质代谢,并在冠心病中有重要发病学意义.     

缺锌儿童体内T淋巴细胞及其相关细胞因子变化的研究

目的探讨缺锌对余杭地区儿童体内T淋巴细胞及相关细胞因子的影响。方法选择当地缺锌（血锌〈75μg/L）儿童43例（缺锌组）和健康儿童40例（健康对照组）,观察身高和体重。采用ELISA法检测血清中γ干扰素（IFN-γ）、白细胞介素-2（IL-2）和白细胞介素-4（IL-4）水平;采用流式细胞术检测CD^3＋T细胞和CD^4＋T细胞。结果缺锌组儿童平均身高和体重均低于健康对照组;缺锌组儿童血清中IFN-γ、IL-2和IL-4和体内CD^3＋T细胞和CD^4＋T细胞水平均显著低于健康对照组（P〈0.05）。结论锌缺乏可影响儿童细胞免疫功能。     

甲醛染毒对雄性大鼠脏器及血清微量元素的影响

目的探讨甲醛染毒对雄性大鼠脏器及血清微量元素的影响.方法选用体重(110～130)g Wistar大鼠40只,随机分为4组, 染毒浓度分别为,高浓度组:(119.6±15.4) mg/m3、中浓度组:(25.2±4.6) mg/m3、低浓度组:(4.8±1.3) mg/m3和对照组;室内空气,采用静式吸入法,每天染毒1h,连续染毒9w后处死,测定大鼠各脏器的脏器系数、甲醛浓度、及大鼠血清中Fe,Cu,Zn的含量.结果高剂量组雄性大鼠肺、肾和肝脏中甲醛浓度明显高于对照组,各染毒组雄性大鼠体重明显低于对照组(P<0.05),高剂量组雄性大鼠各脏器的脏器系数与对照组比较均有显著性差异(P<0.05),雄性大鼠血清中锌含量明显降低、铜含量显著升高(P<0.05).结论长期高剂量吸入甲醛可影响雄性大鼠的生长及其血清Cu、Zn水平,并可损伤雄性大鼠的肝、肺、肾、心、脑、睾丸.     

锌对不同碘营养水平大鼠垂体甲状腺形态学影响的实验研究

目的：观察锌对不同碘营养水平大鼠垂体,甲状腺形态学的影响;方法：缺碘饲料喂养Wistar大鼠复制缺碘动物模型,同时设补碘,补锌和补碘补锌组。3个月时应用光镜和秀射电镜观察垂体和甲状腺超微结构变化。结果：各组垂体重量及光镜下窦样毛细血管和细胞均无明显差异,补碘及补碘补锌组甲状腺细胞,高度。滤泡直径,胶质含量和超微结构与对照组相一致。补锌组甲状腺生理低于缺碘组,上细胞高度及滤泡直径介于缺碘和对照组之间,电镜下缺碘组表现为细胞器明显减少,补锌组则表现为线粒体肿胀,内质网扩张。结论：补锌可降低缺碘大鼠甲状腺肿大程度,对甲状腺上皮细胞具有保护作用。     

丹参酚酸B山楂黄酮联用对大鼠非酒精性脂肪性肝病相关因素的干预作用

[目的]探讨中药成份复方(丹参酚酸B、山楂黄酮)对大鼠非酒精性脂肪性肝病相关因素的影响.[方法]大鼠被随机分为:①正常对照组,普通鼠饲料喂养;②模型组,高脂饲料喂养;③中药预防组,高脂饲料喂养的同时加每天1次灌服丹参酚酸B(200 mg/kg)和山楂黄酮(40 mg/kg);④中药治疗组,高脂饲料喂养4周后加每天1次灌服丹参酚酸B(200mg/kg)和山楂黄酮(40mg/kg);⑤西药组:高脂饲料喂养4周后加每天1次灌服二甲双胍片(0.5 g/kg).实验共12周.[结果]①12周时中药预防组大鼠血清脂联素含量较模型组显著升高(P＜0.01);②各组大鼠血清游离脂肪酸和肿瘤坏死因子-α含量比较差异无统计学意义;③与模型组相比,6、8、12周时,中药预防组和中药治疗组大鼠肝组织三酰甘油含量明显降低(P＜0.01).[结论]丹参酚酸B和山楂黄酮联用对大鼠非酒精性脂肪性肝病相关因素具有干预作用.     

Zinc deficiency impairs T cell function in mice with primary infection of Heligmosomoides polygyrus (Nematoda)

This study was designed to determine whether severe zinc deficiency would prolong the course of a primary Heligmosomoides polygyrus infection in mice, and whether this could be related to impaired T cell function. Female BALB/c mice were fed a zinc-sufficient (Zn+; 60 mg/kg), a zinc-deficient (Zn-; 0.75 mg/kg) or an energy restricted (PF; 60 mg zinc/kg) diet. After four weeks, some mice in each dietary group were given a primary infection with 100 larvae; nutritional, parasitological and immunological parameters were assayed over the following five weeks. Liver zinc concentrations were significantly reduced in Zn- mice compared with Zn+ mice. In certain cases, PF mice also had reduced liver zinc concentrations, showing the negative effects of restricted food intake on zinc status. Zinc deficiency prolonged the course of a primary infection, with the effects being most evident five weeks post-infection when Zn+ mice had only 40% as many worms as Zn- mice. Parasite infection induced strong immunological responses in Zn+ mice in contrast to Zn- mice. The reduced production of IL-4 and IFN-γ, the reduced peripheral eosinophilia and reduced serum levels of IgE and IgG1 in Zn- mice were attributed to the zinc deficiency, whereas the reduced delayed type hypersensitivity response to parasite antigen and reduced production of IL-5 were in certain instances attributed to reduced energy intake rather than zinc deficiency. These results show that zinc deficiency significantly impairs functions normally attributed to both Th1 and Th2 cell populations, and that these alterations are associated with elevated worm numbers in zinc-deficient mice.     

缺锌对大鼠肠粘膜超微结构的影响

目的:为了解决缺锌时肠道粘膜的形态及结构的变化情况.方法:本文通过建立缺锌、常锌大鼠模型,对大鼠肠道粘膜的超微结构进行研究,结果;①第四周末和第七周末血浆、红细胞膜和肠组织的锌含量,ZD(Zinc-Deficiency)组明显低于ZN(Zinc-Normal)组;③第四周末和第七周末ZD组光镜下肠粘膜未见异常改变;但是电镜下见肠道粘膜严重的超微结构损害.结论:可见缺锌对肠道粘膜的结构有严重的影响.因此,机体应保持适当的锌摄入,对人们(尤其是儿童和老年)健康保健和临床相关疾病的治疗具有非常重要的意义.     

Continuous administration of growth hormone does not prevent the decrease of IGF-I gene expression in zinc-deprived rats despite normalization of liver GH binding

To determine the role of reduced liver GH binding (GHR) in the decreased IGF-I observed in zinc-deficient (ZD) animals, we investigated the effects of GHR restoration on growth, insulin-like growth factor I (IGF-I) and its binding proteins (IGFBPs) in ZD rats. Rats were fed for 4 weeks a zinc-deficient diet (ZD Zn, 0 ppm) or a Zinc-normal diet (pair-fed or PF; Zn, 75 ppm). ZD rats received continuous s.c. infusion of bovine growth hormone (bGH) (100 microg/d) for the 4 weeks or for the last week of the study. Compared with pair-fed rats, zinc deficiency produced attenuated weight gain (-43%, P < 0.001), lower serum IGF-I and liver IGF-I mRNA (-52%, P < 0.001 and -44%, P < 0.05), lower serum IGFBPs (IGFBP-3 -66%, IGFBP-4 -48%, 34-29 kDa IGFBP cluster -53%, P < 0.05), lower liver GHR and its mRNA (-20 and -34%, P < 0.05) and lower serum growth hormone binding protein (GHBP) and its mRNA (-56 and -48%, P < 0.05; all comparisons vs PF rats). Exogenous bGH given continuously normalized the liver GHR, serum GHBP and their liver mRNAs, as well as circulating IGFBPs. Despite restoration of GHR and GHBP to normal, growth, serum IGF-I and its liver mRNA were not stimulated by GH infusion in ZD rats, indicating that IGF-I synthesis requires the presence of zinc in addition to GH, and that the lack of growth-promoting action of GH in zinc-deprived rats results from a defect beyond GH binding to its liver receptors.     

Effect of zinc deficiency on serum somatomedin levels and skeletal growth in young rats

We have studied potential mechanisms by which zinc deficiency (ZD) may result in growth impairment in young animals. Dietary-induced ZD in young rats resulted in diminished skeletal growth as measured by tibial epiphyseal width. Treatment with bovine GH (bGH) did not increase skeletal growth suggesting GH resistance rather than GH deficiency in zinc-deficient rats. Serum levels of basic somatomedin (SM) were lower in zinc-deficient rats than in control rats receiving a zinc adequate diet, either ad libitum or in pair matched amounts, and were restored to normal by zinc repletion but not by bGH treatment, suggesting that SM production is impaired by ZD. There was a high correlation between tibial epiphyseal widths and serum or femur zinc concentrations. These findings, along with observations that despite similar levels of serum basic SM the bGH-treated zinc-deficient rats had smaller tibial epiphyseal widths than pair fed control rats, additionally suggest that the action of SM on skeletal growth is impaired by ZD.     

Zinc deficiency exaggerates diabetic osteoporosis

Streptozotocin diabetic rats showed an increase of bone fragility (11.9 ± 2.1 kg/cm² vs. 16.8 ± 2.0, P < 0.005) which was normalized by insulin treatment (18.3 ± 4.2), indicating that osteoporosis was induced in diabetic rats. The rats were fed a zinc-deficient diet (0.16 mg/100 g) or a control diet (5.2 mg/100 g). This mild zinc-deficient diet did not lower the serum zinc level. The cortical bone of diabetic rats was shown to be markedly thinner by microscopic examination of ground cross-sections of the tibia. Zinc deficiency induced a reduction in the calcium content of diabetic bone when compared with the rats on a control diet. Urinary excretion of calcium and phosphorus was significantly increased in diabetic rats, and increased further when the rats were fed a zinc-deficient diet. Moreover, the bone calcium and phosphorus concentrations were significantly lower in these animals. These changes in the zinc-deficiency rats were not reversed by insulin treatment. Our findings suggest that osteoporosis in the diabetic rats was due to thinning of the bone cortex secondary to mineral loss and can be reversed by insulin treatment, and that these skeletal changes are greatly enhanced by mild zinc deficiency. In addition, the effects of zinc deficiency cannot be completely reversed by insulin treatment.     

Regulation of metabolic rate and substrate utilization by zinc deficiency

The trace metal zinc (Zn) is essential for the catalytic activity of many enzymes involved in energy nutrient metabolism and appears to regulate hormones, such as insulin, leptin, and thyroid hormone that play key roles in metabolism. Thus, this study used the continuous monitoring of oxygen consumption, carbon dioxide production, locomotion, and food intake to determine the effect of dietary Zn restriction on metabolic rate (MR), basal metabolic rate (BMR), and respiratory quotient (RQ). Rats were fed a Zn-adequate (ZA, 28 ppm) or Zn-deficient (ZD, <1 ppm) diet for 8 days, followed by a 4-day refeeding period. To control for reductions in food intake that characteristically occur in ZD rats, an additional group was pair-fed (PF) the same amount ZA food eaten by ZD rats. The mean caloric intake of ZD rats was significantly lower than ZA rats by day 3. By day 8, ZD and PF rats weighed 64% and 67% of ZA rats, respectively, (P <.01). Pair feeding resulted in increased locomotor activity, such that the distance traveled for PF rats (316 +/- 43 m) was 6 times that of ZA (53 +/- 6 m). Despite the fact that PF and ZD rats had the same food intake, there was no increase in locomotor activity in ZD rats suggesting that the mechanisms responsible for increased physical activity in food restricted animals may be Zn dependent. Furthermore, differences in activity between PF and ZD animals were not reflected in differences in MR. Both ZD and PF significantly reduced MR compared with ZA rats beginning on day 4. There was a significant relationship between RQ and caloric intake (r = 0.708, P <.01), but no specific effect of Zn status. Thus, while there may be an effect of Zn on locomotion and the energetic cost of activity, it appears that the most profound effect of Zn status on MR and substrate utilization is the result of Zn deficiency-induced anorexia.     

Zinc Deficiency Anemia and Effects of Zinc Therapy in Maintenance Hemodialysis Patients

Quantitative adjuvant zinc therapy using polaprezinc was performed to examine the correlation between zinc concentration and anemia in maintenance hemodialysis patients to propose appropriate treatment. Anemia and serum zinc concentration were measured in 117 patients with chronic renal failure receiving outpatient maintenance hemodialysis at Tsuyama Chuo Kinen Hospital. Two bags of polaprezinc (containing zinc 34 mg/day) were administered to 58 patients with lower than normal zinc levels (Zn < 80 mg/dl) as adjuvant zinc therapy to assess anemia improvement. Zinc concentration and all anemia parameters showed significant positive correlation, indicating that anemia improves in patients with high serum zinc levels. Regarding the effects of adjuvant zinc therapy for improving anemia, hemoglobin levels were found to increase significantly to the highest value at 3 weeks. During treatment, the dosage of erythropoietin was reduced significantly from baseline at all assessment points. No zinc poisoning from therapy was seen, but two patients had diarrhea (1.9%). Zinc‐treated patients required iron therapy due to the development of iron deficiency. Most maintenance hemodialysis patients suffer from zinc deficiency anemia, and zinc‐based polaprezinc has been confirmed to be an effective and safe adjuvant zinc treatment. Most patients diagnosed as refractory anemia with no response to erythropoietin also suffer from zinc deficiency anemia, many of whom are expected to benefit from zinc therapy to improve their anemia. Possible zinc deficiency anemia should be considered in the treatment of refractory anemia with no response to erythropoietin.     

The influence of marginal zinc deficient diet on post-vaccination immune response against hepatitis B in rats.

AIM: To evaluate in vitro T lymphocyte proliferation and specific antibody response to hepatitis B vaccination in two groups of rats fed with normal and marginal zinc content. METHODS: Twenty-two Wistar-Albino rats were randomly assigned into two groups and were fed with constant diet. Zinc was suplemented 10mg/kg dry weight in group I (marginal zinc content) (n=14) and 30mg/kg dry weight in group II (n=8). Hepatitis B vaccine (Engerix B, 4mug) was administered intramuscularly after 8 weeks on feeding and a booster dose was applied 4 weeks after the first injection. Rats were killed 3 weeks after the second injection. Peripheral blood mononuclear cells were stimulated in vitro by PHA (2.5mug/ml) and hepatitis B surface antigen (2.5, 5, 10mug/ml). Proliferation was evaluated by ELISA (celltiter-96 aqueous one solution cell proliferation assay). Serum zinc, anti-HBs titer and zinc per dry liver weight were also measured. Two groups were compared with respect to antigen specific antibody and lymphocyte proliferation responses. Proliferation response to HbsAg were expressed as net percent increase (pci) in lymphocyte proliferation from the baseline activity. RESULTS: Rats' mean body weight and weight gain per month were similar. Median serum zinc was 39 (23-75) and 76(64-115)mug/dl of groups I and II rats, respectively (p<0.05), while there was no difference in liver zinc content between the two groups (37mug/g dry weight versus 32mug/g dry weight). Median anti-HBs levels of groups I and II were 741 (0-10,000)IU/l, 5791 (558-10,000)IU/l, respectively (p<0.05). In lymphocyte proliferation assays, mean net pci with HbsAg of 5 and 10mug/ml were 9.4% and 11.3% in group I rats; while they were 25.3% and 26.1% in group II rats (p<0.01 and p<0.01, respectively). CONCLUSION: In vitro cell-mediated immune response and in vivo specific antibody response to hepatitis B vaccine was decreased in rats fed a diet with marginal zinc content. These observations have shown that marginal Zn deficiency might influence the efficacy of hepatitis B vaccination in humans.     

Knockout mice reveal a tumor suppressor function for Testin

The Testin (TES) gene was previously identified as a putative human tumor suppressor gene at 7q31.2, a region that is frequently deleted in hematopoietic malignancies, as well as in epithelial tumors. To determine whether TES acts as a tumor suppressor in vivo, we generated a Tes knockout mouse and then used it in an established model of carcinogen-induced gastric cancer. In mice a zinc-deficient (ZD) diet enhances cellular proliferation in the forestomach and susceptibility to N-nitrosomethylbenzylamine (NMBA)-induced carcinogenesis. Five-week-old Tes wild-type (+/+), heterozygous (+/-), and homozygous (-/-) mice were divided into four groups: mice fed a zinc-sufficient diet (ZS); mice fed a ZD diet; ZS fed plus NMBA-treated mice (ZS+NMBA), and ZD fed plus NMBA-treated mice (ZD+NMBA). After 4 weeks, the ZS+NMBA and ZD+NMBA groups were treated with three intragastric doses of NMBA. Animals were killed 8 weeks after NMBA administration: 25% of +/+ mice developed benign lesions; 88% of +/- showed multiple papillomas, atypical glandular metaplasia, and squamous cell carcinomasl; and 81% of -/- mice displayed very large papillomas, squamous cell carcinomas, and adenocarcinomas. A statistically significant difference in tumor incidence was found between +/- versus +/+ and -/- versus +/+ (P < 0.0001). These data suggest that Tes functions as a tumor suppressor gene in vivo.