硫辛酸对高脂日粮小鼠消化系统自由基清除作用研究

目的研究硫辛酸(LA)对高脂日粮小鼠消化系统自由基生成及机体抗氧化能力的影响。方法选取6w龄雌性昆明种小鼠40只,随机平均分成4组:即正常对照组(正常日粮),高脂日粮组(高脂日粮),LA组(高脂日粮+0.05%LA和高脂日粮+0.1%LA)。6w后测定小鼠血液、胃、胰腺、十二指肠、空肠及回肠自由基水平和机体抗氧化指标。结果饲喂高脂日粮可显著提高小鼠血液、胃、胰腺、十二指肠、空肠及回肠自由基水平,显著降低小鼠机体抗氧化能力,添加0.05%LA对高脂日粮小鼠消化系统自由基清除及抗氧化能力的提高作用不显著,添加0.1%LA可使高脂日粮小鼠血液及组织自由基水平和抗氧化能力恢复到正常日粮组水平。结论高脂日粮摄入,增加小鼠消化系统自由基的生成,降低机体抗氧化能力,适量的LA添加可有效清除高脂日粮小鼠消化系统自由基,提高机体抗氧化能力,缓解营养性氧化应激。     

硫辛酸对高脂饲养小鼠氧化应激及血糖血脂的影响

目的研究高脂日粮和硫辛酸(lipoic acid,LA)对不同饲养阶段小鼠氧化应激和血糖血脂的影响。方法 6w龄雌性昆明小鼠130只,随机分为3组:即正常饲料组(Cont)50只,高脂饲料组(HFD)40只,高脂饲料+0.1%硫辛酸组(HFD+0.1%LA)40只,在0w时处死Cont组小鼠10只,之后分别在实验第1w、2 w、4 w、8w末处死3组小鼠各10只,测定血、肝脏、肌肉组织活性氧(ROS)水平、氧化应激和血糖(BG)、血脂指标。结果与实验开始时相比,随着饲养时间的增加,Cont组小鼠全血、肝脏和肌肉ROS和丙二醛(MDA)水平逐渐升高,过氧化氢酶(CAT)和总抗氧化能力(T-AOC)水平逐渐下降,在第8w时差别有统计学意义(P<0.05),HFD和HFD+LA组也呈现出类似趋势。与Cont组相比,HFD组ROS和MDA,BG,血脂水平均高于同期Cont组,CAT和T-AOC均低于同期Cont组,在第8w时差别有统计学意义(P<0.05)。HFD+LA组表现出与HFD组相似的趋势。结论随着饲养时间的增加,HFD组小鼠出现营养性氧化应激,血糖、血脂代谢紊乱,LA通过清除ROS改善高脂日粮小鼠机体氧化还原状态,改善血糖、血脂代谢紊乱。     

高脂日粮介导小鼠十二指肠氧化应激与肠钙吸收的关系

目的探讨高脂日粮对小鼠十二指肠氧化还原状态与肠钙吸收的影响及其相关性。方法50只5周龄C57BL/6雄性小鼠,体重13～14g,根据体重随机分为对照组(0.6%Ca,w/w),高脂日粮组(19.64%猪油,0.6%Ca),添加0.1%硫辛酸(LA)高脂日粮组,钙补充高脂日粮组(1.6%Ca)和添加0.1%LA钙补充高脂日粮组,饲养8w,最后1w,通过代谢实验评价钙吸收情况,并检测血和十二指肠的活性氧(ROS)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、丙二醛(MDA)、还原型/氧化型谷胱甘肽(GSH/GSSG)和总抗氧化能力(T-AOC)等氧化应激相关指标。结果高脂日粮导致C57BL/6小鼠十二指肠氧化应激并且减少肠钙吸收。钙净吸收与十二指肠的GSH/GSSG(r=0.801,P0.01)、T-AOC(r=0.777,P0.05)呈正相关,而与ROS(r=-0.716,P0.05)呈负相关。结论高脂日粮导致十二指肠氧化应激是肠钙吸收减少的重要原因。     

硫辛酸对高脂饲料小鼠氧化应激与糖、脂代谢基因表达的影响

目的探讨硫辛酸(LA)对高脂饲料小鼠血糖、血脂代谢和抗氧化能力的影响。方法24只C57BL/6雄性小鼠,随机分为3组:即对照组(正常饲料),高脂组(高脂饲料),LA组(高脂饲料+0.1%LA),6周后测定空腹血糖(FPG)、胰岛素(FINS)、甘油三酯(TG)、总胆固醇(TC)等糖脂代谢指标以及丙二醛(MDA)、超氧化物歧化酶(SOD)和总抗氧化能力(TAC)等抗氧化指标,同时用Affymetrix MOE430A基因芯片分析肝脏抗氧化、糖脂代谢相关功能基因的表达。结果与高脂组相比,LA组MDA含量显著降低,TAC明显升高(P<0.05)。LA显著降低血浆TG、TC、LDL-C和FPG、FINS的水平(P<0.05),MDA含量与HDL-C/TC(r=-0.47,P<0.05)和胰岛素抵抗指数(r=0.74,P<0.05)显著相关。硫辛酸改变高脂组自由基/氧化应激、糖脂代谢相关通路大部分响应基因的表达水平。结论高脂引发氧化-抗氧化系统失衡,硫辛酸通过直接清除自由基以及恢复自由基/氧化应激通路相关基因的表达水平解除氧化应激而有助于防治高脂引发的糖脂代谢紊乱。     

大蒜素对小鼠脾脏T淋巴细胞亚群影响的实验研究

目的观察大蒜素对小鼠脾脏指数及其T淋巴细胞亚群分化的影响。方法将80只清洁级昆明小鼠随机化分组:生理盐水对照组、大蒜素低剂量组、大蒜素中剂量组和大蒜素高剂量组,每组20只,并分别按0.1ml/(10g bw)、100mg/(kg bw)、200mg/(kg bw)、400mg/(kg bw)的剂量连续灌胃14d,每天灌胃1次并称重。灌胃结束7d后处死小鼠,无菌分离脾脏称重,计算脾脏系数,制作单细胞悬液,采用流式细胞仪检测小鼠T淋巴细胞亚群中CD4~+T淋巴细胞、CD8~+T淋巴细胞和CD4~+/CD8~+的值。结果大蒜素中、高剂量组和生理盐水对照组比较,脾脏指数、脾脏淋巴细胞CD4~+T淋巴细胞比例和CD4~+/CD8~+值均升高,CD8~+T淋巴细胞比例降低,差异有统计学意义(F=5.52,P0.05),而大蒜素低剂量组与生理盐水对照组比较,脾脏指数、脾脏淋巴细胞CD4~+T淋巴细胞、CD8~+T淋巴细胞和CD4~+/CD8~+值差异无统计学意义(F=1.87,P0.05)。结论大蒜素能够使得小鼠脾脏指数、脾脏淋巴细胞CD4~+T淋巴细胞比例和CD4~+/CD8~+值均升高,CD8~+T淋巴细胞比例降低,对正常小鼠脾脏免疫功能具有正向调节作用。     

低聚木糖对摄食高脂饲料的小鼠自由基水平及抗氧化作用的影响

目的研究高脂饲料条件下,不添加和添加中、高剂量(0.0835%和0.1650%)的低聚木糖(XOS)对小鼠体内自由基及抗氧化功能的影响。方法将24只小鼠分成4组,设置对照,通过向高脂饲料中添加XOS,观察对小鼠机体自由基及抗氧化功能的影响。结果与正常对照组相比,高脂饲料可导致小鼠氧化应激,升高体内自由基水平,降低机体抗氧化能力,而添加XOS的饲料能显著降低机体自由基水平,增强血清及组织中SOD、GSH-Px及CAT活性,显著升高血清T-AOC水平,显著降低血清MDA含量。并且,XOS添加量与抗氧化作用呈现量效关系。结论低聚木糖具有较好的清除机体自由基及抗氧化功能。     

高脂日粮对小鼠肠道基因表达谱的影响

目的探讨长期饲喂高脂日粮对小鼠肠道基因表达谱的影响。方法16只C57BL/6雄性小鼠,体重约12～13g,饲喂正常日粮1w后,根据体重随机分为正常对照组(正常日粮)和高脂组(高脂日粮),饲养6w,眼球采血宰杀小鼠,迅速分离空肠一段,同组4只小鼠的约100μg空肠合并在一起,应用含13097寡核苷酸探针的小鼠Affymetrix MOE430A基因芯片检测肠道基因表达的改变。结果与对照组相比,模型组共出现267条差异表达基因,这些差异表达的基因主要涉及自由基/氧化应激、DNA修复、细胞凋亡、物质转运、细胞信号转导和炎症/免疫反应等相关基因。结论长期高脂日粮可能通过影响小鼠肠道氧化还原状态,广泛调控肠道多种基因表达。     

农达对小鼠脾脏淋巴细胞亚群和氧化应激状态的影响

目的探讨农达(roundup,活性成分为草甘膦)对小鼠脾脏淋巴细胞亚群和氧化应激状态的影响。方法将48只成熟SPF级雄性Balb/c小鼠随机分为阴性对照(蒸馏水)组和20、200、2 000 mg/kg农达染毒组,每组12只,灌胃染毒0.02ml/g,每日1次,连续染毒30 d。计算脾脏系数,采用流式细胞仪分析小鼠脾脏CD3~+、CD4~+、CD8~+T细胞,CD45r~+B细胞,CD49b~+NK细胞比例并计算CD4~+T/CD8~+T比值;测定小鼠脾脏中丙二醛(MDA)含量和超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活力。结果染毒30 d后,各农达染毒组小鼠脾脏重量呈下降趋势;与阴性对照组相比,200、2 000mg/kg农达染毒组小鼠脾脏CD3~+、CD4~+、CD8~+T细胞比例明显升高,CD45r~+B细胞比例明显下降,200 mg/kg农达染毒组CD4~+T/CD8~+T比值下降,差异有统计学意义(P0.01)。各染毒组小鼠脾脏中MDA含量均增加,GSH-Px活力均降低,差异有统计学意义(P0.01)。结论除草剂农达可能通过影响小鼠脾脏淋巴细胞亚群和氧化应激状态,抑制小鼠免疫功能。     

克山病病区粮及硒补充对小鼠免疫功能的影响

用克山病病区粮和在病区粮中补加不同水平硒的饲料喂养C_(57)BL/6J断乳小鼠7周,病区粮组小鼠脾脏免疫特异玫瑰花形成细胞(RFC)数、溶血空斑形成细胞(PFC)数、脾脏淋巴细胞介导的体外绵羊红细胞溶血反应(QHS)均明显低于非病区粮组,病区粮补硒各组小鼠的上述免疫反应虽有增强,但未达到非病区粮对照组水平。提示补硒只能部分改善病区粮致病因素对免疫功能的抑制作用。     

外源核苷酸对小鼠免疫功能的影响

目的 :　本实验研究了日粮核苷酸促进免疫抑制小鼠的免疫功能恢复的作用。方法 :　选取 5～ 6 w龄 ,体重为 (2 0± 2 ) g的健康昆明种小鼠 6 0只 ,设 0、0 .0 5 %、0 .2 5 %三个核苷酸水平处理 ,每个处理中又分成正常和免疫抑制两个组 ,其中所有免疫抑制组在实验的第 2 d一次性大剂量腹腔注射环磷酰胺 (1 5 0 mg/kg bw) ,制备免疫抑制模型 ;正常组注射等同剂量的生理盐水。饲养 1 0 d后观察小鼠增重、脾脏和胸腺的脏器指数、脾淋巴细胞转化率、脾脏中抗 SRBC抗体形成细胞数量以及血清中抗 SRBC抗体水平。结果 :　日粮中添加核苷酸能够提高正常小鼠的增重 (P<0 .0 5 )、胸腺指数、淋巴细胞转化率 (P<0 .0 5 )及血清中抗体水平 ,极显著提高免疫抑制小鼠抗体水平 (P<0 .0 1 ) ,使抑制小鼠的各项指标接近正常。抗 SRBC抗体形成细胞数量没有显著变化。结论 :　在无核苷酸日粮中添加核苷酸能够促进正常小鼠免疫功能的提高 ,使免疫抑制小鼠免疫功能得到改善。     

Lipoic acid attenuates high-fat-diet-induced oxidative stress and B-cell-related immune depression

ObjectiveThis study investigated whether spleen oxidative stress induced by a high-fat diet (HFD) influences the expression of genes involved in B-cell activation, thus leading to B-cell–related immunosuppression.MethodsMale C57BL/6 mice were randomly assigned to one of three groups with eight mice in each group. The control group consumed an ordinary diet (4.9% fat, w/w). The other two groups were fed an HFD (21.2% fat) and an HFD plus 0.1% lipoic acid (LA). After 10 wk, plasma and spleen oxidative stress biomarkers including superoxide dismutase, catalase, glutathione peroxidase, total antioxidant capacity, reduced glutathione/oxidized glutathione ratio, and malondialdehyde were examined. The B-cell–related immune function was evaluated by examining the number of B cells, and the apoptotic percentages of splenic lymphocytes were determined by flow cytometry. Furthermore, the B-cell activation and reactive oxygen species scavenger-related genes differentially expressed between mice fed an HFD and those fed an HFD supplemented with LA were identified through complementary DNA microarray.ResultsThe HFD induced marked decreases in the number of B cells and significantly increased the apoptotic percentages of splenic lymphocytes, accompanied by oxidative stress and increased oxidative damage, in the plasma and spleen. In addition, complementary DNA array analysis results showed that the HFD induced the decreased expression of genes associated with antioxidant defense, such as superoxide dismutase-3 (1.5-fold), metallothionein-1 (3.03-fold), glutathione peroxidase-5 (17.15-fold), and peroxiredoxin-4 (1.5), and B-cell activation, such as immunoglobulin heavy chain 6 (2.46-fold), immunoglobulin κ-chain (1.74-fold), Fc receptor (1.41-fold), and RAS-related C3 botulinum substrate-1 (7.46). The LA supplement prevented the buildup of oxidative stress and upregulated related gene expressions.ConclusionThese results indicate a role for LA as a possible effective supplement with an HFD to prevent the development of oxidative stress and to attenuate B-cell damnification by increasing the gene expression of the B-cell receptor signaling pathway.     

牛磺酸与高脂膳对二甲基苯蒽诱发大鼠乳癌的影响

目的 :　探讨牛磺酸和 /或高脂饲料对二甲基苯蒽 ( DMBA)诱发大鼠乳腺癌的影响 ,初步探讨其可能的机制。方法 :　初断乳雌性 SD大鼠 1 0 1只 ,随机分为牛磺酸组 ( Tau)、牛磺酸 +高脂组 ( TH)、高脂组 ( HF)和对照组 ( CL) ,于 6w龄灌胃给予 DMBA后 ,分别饲以不同饲料。实验期 2 6w,实验结束时处死全部动物 ,检查肿瘤发生情况并进行血清抗氧化、血脂及免疫学指标检测。结果 :　Tau组乳腺肿瘤发生率低于 HF组而与 CL组差异未见显著性 ;平均瘤重 Tau组低于 CL组和 HF组 ;各组肿瘤平均潜伏期未见明显差异。与 CL组比较 ,Tau组血清 SOD、GSH- Px活力增高 ,LDL- C、MDA含量下降 ;HF组可见 GSH- Px活力和抗体生成能力下降 ,血清 TC升高 ;而添加了 Tau的高脂饲料组 ( TH)则仅出现了 GSH- Px活力的下降。结论 :　膳食中补充 5 %牛磺酸对诱发肿瘤的生长具有一定的抑制作用 ,并在一定程度上对抗高脂膳食的促癌作用。该作用可能是通过调节免疫功能、增强抗氧化能力及调节脂代谢等多种途径实现的     

Lymphocyte subpopulations in the thymus, lymph nodes and spleen of iron-deficient and rehabilitated mice

Three groups of weanling female mice were fed one of two iron-deficient diets (5 and 12 mg Fe/kg diet) or a normal diet (30 mg Fe/kg diet) for 6 wk. A control pair-fed group was included. Seven mice received the 5 mg Fe/kg diet for 6 wk, then were rehabilitated using the 30 mg Fe/kg diet for 10 d. Mice fed the 5 mg Fe/kg diet were moderately iron-deficient, as shown by indices of iron status. No significant differences were observed in thymus weight or in the proportion and number of thymocyte subsets in thymuses of anemic, moderately iron-deficient and control mice. Thymus weight was decreased in pair-fed mice. No significant difference was found in lymph node subsets. In the spleen of anemic mice, the proportions and total number of Thy-1+ splenocytes, CD4-8+ and CD4+8- cells were very low compared with control (P less than 0.01) and iron-deficient (P less than 0.02) mice. The decrease was not only observed for the percentage of subsets but also for the absolute number of cell subtypes per spleen. Thy-1+ splenocyte subpopulations were normalized after rehabilitation. These quantitative modifications could explain alterations in the blastogenic response of splenic lymphocytes described by other authors.     

褪黑素改善高糖高脂饲养大鼠胰岛素敏感性

目的:观察褪黑素对高糖高脂饲养大鼠胰岛素敏感性的影响。方法:将18只雄性SD大鼠(150~200g)随机分为正常组(CD组)与高糖高脂组(HFSD组),分别饲以正常饲料与高糖高脂饲料(53%基础饲料含蔗糖37%和猪油10%)喂养6个月后,给药治疗2个月;治疗期间,给褪黑素组(Mel组)每天腹腔注射药物褪黑素(Melatonin,Mel,4 mg/kg),对照组腹腔注射生理盐水。测定空腹血糖、胰岛素、甘油三酯(TG)、游离脂肪酸(FFA)、高密度脂蛋白胆固醇(HDL—C)水平,做口服葡萄糖耐量实验(OGTT)和胰岛素敏感性实验。结果:高糖高脂饮食可诱导SD大鼠产生胰岛素抵抗,引起SD大鼠空腹血糖、血清胰岛素、TG、FFA水平升高;胰岛素敏感性、HDL—C水平下降。褪黑素治疗后,胰岛素敏感性增强,改善了胰岛素抵抗。结论:Mel能降低高糖高脂饲养SD大鼠糖脂状况,提高胰岛素敏感性,改善胰岛素抵抗。     

Effects of reduced dietary linoleic acid intake, alone or combined with an algal source of docosahexaenoic acid, on MDA-MB-231 breast cancer cell growth and apoptosis in nude mice

Diets rich in linoleic acid (LA), an n-6 fatty acid, stimulate the progression of human breast cancer cell solid tumors in athymic nude mice, whereas docosahexaenoic acid (DHA) and eicosapentaenoic acid, long-chain n-3 fatty acids, exert suppressive effects. In the present study we used a novel source of DHA, in triglyceride form, to determine the effects of feeding low levels of the fatty acid on the growth of MDA-MB-231 cells injected into the thoracic mammary fat pads of female nude mice. Four different isocaloric diets were used, all of which provided 20% (wt/wt) total fat. The control diets contained 8% (20 mice) or 4% (50 mice) LA; the n-3 fatty acid-supplemented groups of 50 mice were fed 4% LA-containing diets plus 2% or 4% DHA. The tumor growth rates were reduced significantly in mice fed the 4% LA compared with the 8% LA diet; the addition of 4% DHA to the 4% LA-containing diet produced a further reduction in tumor growth rate (p < or = 0.003 at and after Week 6). The final tumor weights were also reduced in the DHA-fed mice compared with the 8% LA dietary group (2% DHA, p = 0.02; 4% DHA, p = 0.01) and in the 4% DHA-fed mice compared with the 4% LA control group (p = 0.02); a similar trend for mice fed the lower level of DHA did not achieve statistical significance. Tumor prostaglandin E2 concentrations were reduced by feeding the lower LA level; further dose-dependent decreases occurred in the DHA dietary groups and were accompanied by reduced levels of 12- and 15-hydroxyeicosatetraenoic acids. These changes in eicosanoid biosynthesis may have been responsible for the observed decreases in cell proliferation, indicated by suppressed Ki-67 expression, and increases in apoptotic activity, as reflected in TdT-mediated dUTP nick end labeling immunohistochemical staining.     

Acanthopanax senticosus extract prepared from cultured cells decreases adiposity and obesity indices in C57BL/6J mice fed a high fat diet

The herb Acanthopanax senticosus was cultured from a cell suspension by a proprietary process, and evaluated for protective effects against obesity in C57BL/6J mice fed high fat diets. Forty 4-week-old male C57BL/6J mice (n = 10) were fed either a normal diet (10 kcal fat%) or high fat diet (60 kcal fat%) given with or without oral administration of A. senticosus extract (ASE; 0.5 g/kg of body weight) for 12 weeks. Feed consumption was not different among the groups, but energy intake was higher in the groups fed high fat diets than in the groups fed normal diets. Body weight gain, abdominal fat accumulation, and serum leptin concentrations were significantly higher in the high fat-fed groups than the other groups. Animals fed the high fat diet had significantly higher low-density lipoprotein (LDL)-cholesterol in serum and higher triglyceride accumulation in liver, but the ASE supplement restored both to the same levels as in the animals fed low fat diets. Total carnitine concentration were not significantly different between the two diet groups; also the oral administration of ASE did not alter carnitine status. Accordingly, the current results suggest the oral administration of ASE seemed to lower the weight gain, serum LDL-cholesterol concentration, and liver triglycerides accumulation in mice with obesity induced by high fat diets. These results seemed to suggest that supplementation with ASE might have a role in the prevention of obesity in high fat-fed mice.