富硒酵母对CCl4肝损伤小鼠免疫功能的影响

目的:研究富硒酵母对CCl4肝损伤小鼠免疫功能的影响.方法:将50只小鼠随机分为空白组、模型组、硒酵母组、维生素E(VE)组和混合绀(混合喂食硒酵母和VE),每组10只.空白组和模型组灌胃蒸馏水,硒酵母组灌胃富硒酵母,VE组灌胃VE,混合组同时灌胃和硒酵母组、VE组等量的酵母和VE,连续30 d.实验结束后一次性给予8 g/LCCl4的香油溶液5 mL/kg,空白组给香油.然后测定小鼠T和B淋巴细胞转化率、NK细胞活性和巨噬细胞的吞噬功能.结果:富硒酵母能够显著提高小鼠T和B淋巴细胞转化率、NK细胞活性和巨噬细胞的吞噬功能,且和VE具有协同作用.结论:富硒酵母能提高CCl4肝损伤小鼠的免疫功能.     

不同剂量铁对小鼠肝脏损伤作用的实验研究

目的探讨不同剂量的右旋糖酐铁对小鼠肝脏抗氧化水平和病理损伤的影响。方法将雌雄各半的昆明小鼠随机分为4组，以不同浓度的右旋糖酐铁隔日腹腔注射（IP），注射6周后，测定肝组织中丙二醛（MDA）的含量、超氧化物歧化酶（SOD）以及谷胱甘肽过氧化物酶（GSH-PX）的活性，测定血清谷丙转氨酶（ALT）、谷草转氨酶（AST）、碱性磷酸酶（AKP）、酸性磷酸酶（ACP）活性，并做肝脏病理组织学检查。结果与正常对照组相比，肝组织中MDA的含量较对照组明显升高（P〈0．001），SOD和GSH-PX的活性则明显下降（P〈0．001）。血清ALT、ANT活性较对照组明显升高（P〈0．001），且有剂量效应关系；而血清AKP、ACP活性较对照组则无显著性差异（P〉0．05）。病理组织学检查，经铁染色后镜下可见低剂量组有少量铁均匀分布，中高剂量组则有大量铁存在。结论过量的铁可对肝脏造成严重的损害，且呈剂量依赖性，其机制可能与铁在肝脏内代谢释放出铁离子，游离的铁离子介导脂质过氧化而造成肝脏损害有关。     

铜过量小鼠肝损伤模型的建立及各项指标的观察研究

目的探讨昆明小鼠在不同剂量的铜负荷时所引起的肝脏抗氧化水平和相关病理的改变。方法32只昆明小鼠平均分为4组，第1组为对照组，每天灌胃生理盐水2次，第2、3、4组作为实验组，分别用不同浓度（12．8、25．6和38．4mg／mL）的硫酸铜每日灌胃2次，16周后，观察肝组织中丙二醛（MDA）含量、超氧化物歧化酶（SOD）以及谷胱甘肽过氧化物酶（GSH-Px）的活性，测定血清谷丙转氨酶（ALT）和谷草转氨酶（AST）以及血清和肝组织中铜含量，并做肝脏病理以及电镜检查。结果与正常对照组相比，实验组肝组织中MDA含量明显升高（P〈0．05），而SOD和GSH-Px活性明显下降（P〈0．05）；血清ALT、AST活性以及血清、肝脏铜含量明显升高（P〈0．05）；病理组织学检查可见高剂量铜灌胃组小鼠肝细胞变性坏死以及少量铜颗粒沉积：电镜提示肝细胞核、线粒体等细胞器异常．并可见铜颗粒。结论过量的铜可对肝脏造成损害，其机制可能与释放出的铜离子介导脂质过氧化而造成肝脏损害有关。其病变过程与Wilson’s病相似，可为进一步研究铜代谢异常等疾病提供动物模型。     

铁死亡参与高蛋氨酸饮食诱导ApoE^(-/-)小鼠肝损伤的发病过程北大核心

背景:高同型半胱氨酸可以通过氧化应激、炎症反应和内质网应激等机制促进肝损伤的发生。高蛋氨酸饮食诱导的E型载脂蛋白基因敲除(ApoE^(-/-))小鼠可以引起肝损伤以及体内同型半胱氨酸水平升高,铁死亡是一种依赖于细胞内的铁并引起脂质过氧化物过量蓄积的细胞调节性死亡途径。然而,它是否参与了高蛋氨酸饮食诱导肝损害的形成需进一步研究和探讨。目的:探讨铁死亡在ApoE^(-/-)小鼠高同型半胱氨酸致肝损伤中的作用。方法:12只6-8周龄雄性ApoE^(-/-)小鼠,体质量20-25 g,随机分为对照组和高蛋氨酸组,每组6只,分别采用普通饲料和高蛋氨酸饲料喂养13.5周。喂养结束后通过病理学观察以及肝组织中天冬氨酸转氨酶、丙氨酸转氨酶活性检测评估小鼠肝损伤情况;组织铁检测试剂盒测定小鼠肝组织中的铁离子含量;通过肝组织中丙二醛含量和荧光强度评估小鼠肝组织中脂质过氧化程度;实时荧光定量PCR与Western blotting方法分别检测两组小鼠肝组织中P53和谷胱甘肽过氧化物酶4的mRNA和蛋白表达水平。结果与结论:①与对照组相比,高蛋氨酸组发现大量肝细胞排列紊乱,间隙增大,胞浆疏松的典型肝损伤组织病理学改变;天冬氨酸转氨酶以及丙氨酸转氨酶活性升高(P<0.01);肝组织中铁离子含量增加(P<0.01),丙二醛含量(P<0.01)及荧光强度均增加;②实时荧光定量PCR与Western blotting检测发现,高蛋氨酸组小鼠肝组织中谷胱甘肽过氧化物酶4的表达水平降低(P<0.01),P53的表达水平升高(P<0.05);③提示铁死亡参与高蛋氨酸饮食诱导ApoE^(-/-)小鼠肝损伤的发病过程。     

铁摄入过量对人体健康的影响

铁摄入过量会造成大量铁在机体内蓄积。当正常的铁储存机制不能容纳总的机体铁时,过量的铁会导致组织炎症、多器官的损伤和纤维化,因为铁是自由基反应的催化剂,可将超氧化物和氢氧化物转变为极其活跃的自由基,从而引起氧化反应导致细胞老化和死亡。本文就铁摄入过量与癌症、肝脏疾病、神经变性性疾病、心血管疾病、免疫系统疾病等对人体健康的影响作一综述。     

牡蛎粉对化学性肝损伤保护作用的实验研究

目的探讨牡蛎粉对化学性肝损伤的保护作用.方法对NIH种小鼠每日经口灌胃给予0.15g/kg、0.75g/kg和3.00g/kg的牡蛎粉.4周后,以0.1ml/10g的剂量一次性经腹腔注射给予0.1%CCl4.结果 3.00g/kg剂量组的血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST))水平降低,与CCl4对照组比较(p<0.01);0.75g/kg和3.00g/kg剂量组发生肝细胞气球样变的动物例数明显减少,病变程度减轻,气球样变评分低于CCl4对照组(p<0.01).结论牡蛎粉对CCl4化学性肝损伤具有保护作用.     

冬虫夏草对免疫性肝损伤小鼠模型的保护作用研究

目的:观察冬虫夏草多糖(CP)对免疫性肝损伤小鼠模型的保护作用及其作用机制。方法:序贯注射卡介苗(BCG)和脂多糖(LPS)诱导小鼠产生免疫性肝损伤模型。造模过程中,小鼠每日灌胃(ig)冬虫夏草多糖(125、250、500 mg/kg),共12天。比色法测定血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)的含量、肝匀浆中超氧化物歧化酶(SOD)活力以及丙二醛(MDA)浓度,并作肝组织病理切片观察。采用ELISA法测定肝脏中TNF-α和IL-1的含量。结果:冬虫夏草多糖(125、250、500 mg/kg)ig给药明显降低BCG+LPS诱导的免疫性肝损伤后小鼠血清中升高的ALT和AST水平,抑制肝匀浆中上升的MDA水平和升高降低的SOD活性。显著降低肝脏中TNF-α和IL-1的含量。病理检查结果显示冬虫夏草多糖有明显的保肝作用。结论:冬虫夏草多糖对小鼠免疫性肝损伤有一定的保护作用,其机制可能与降低TNF-α、IL-1的含量、平衡细胞因子有关。     

牡蛎粉对化学性肝损伤保护作用的实验研究

目的　探讨牡蛎粉对化学性肝损伤的保护作用 .方法　对NIH种小鼠每日经口灌胃给予 0 .15g/kg、0 .75g/kg和 3.0 0g/kg的牡蛎粉 . 4周后 ,以 0 .1ml/ 10g的剂量一次性经腹腔注射给予 0 .1?l4.结果　 3.0 0g/kg剂量组的血清丙氨酸氨基转移酶 (ALT)、天门冬氨酸氨基转移酶 (AST) )水平降低 ,与CCl4对照组比较 (p <0 .0 1) ;0 .75g/kg和 3.0 0g/kg剂量组发生肝细胞气球样变的动物例数明显减少 ,病变程度减轻 ,气球样变评分低于CCl4对照组 (p <0 .0 1) .结论　牡蛎粉对CCl4化学性肝损伤具有保护作用     

铁负荷对离体大鼠心脏和分离心室肌细胞的作用

目的：研究水溶性Fe³⁺和透膜的脂溶性Fe³⁺复合物对心肌功能和心肌脂质过氧化水平的影响。方法：采用离体灌流心脏和酶解分离心室肌细胞模型，检测心肌力学指标、乳酸脱氢酶（LDH）、肌酸激酶（CK）、丙二醛（MDA）及冠脉流量等指标。结果：FeCl₃缩短舒张期心室肌细胞长度，5、15 μmol/L FeCl₃增加细胞收缩幅度和速度；FeCl₃使灌流心脏LVDP、±dp/dt_max、心率、冠脉流量增大，对心肌LDH、CK释放量和MDA无明显影响。Fe-HQ使心室肌细胞舒张期长度、收缩幅度和±dL/dt_max减小，引起灌流心脏LVDP、±dp/dt_max、心率、冠脉流量先增加后降低的双相变化，高浓度时可使冠脉流出液LDH和CPK量明显增高，心肌MDA增高，心律失常加重。结论：心肌细胞内铁增加可引起心功能受损和脂质过氧化程度增高，水溶性Fe³⁺对心肌细胞功能的影响较脂溶性Fe³⁺小。     

环孢菌素对超抗原SEB致小鼠肝损伤的保护作用

用超抗原葡萄球菌肠毒素B(SEB)、D-氨基半乳糖(D-GalN)混合腹腔注射Balb/c/小鼠及预先注射过环孢菌素(CSA)的小鼠,动态观察小鼠肝细胞变化和血清TNF,IFN-γ水平及小鼠死亡率。结果发现SEB+D-GalN注射后2h、6h时出现肝细胞凋亡,12h后出现肝坏死,小鼠24小时死亡率达 50％。小鼠血清 TNF2h升到最高,IFN-γ在 6～12h较高。而预注CSA的小鼠上述指标正常。推测SEB+D-GalN对肝细胞的作用是由T细胞介导的,可被CSA抑制。     

Effect of Hepatic Isoferrttins from Iron Overloaded Rats on Lymphocyte Proldzerative Response: Role of Ferritin Iron Content

Abstract

Iron and ferritin impair a variety of immunological functions. To evaluate the effect of ferritin iron content on rat lymphocyte proliferative response, isoferritins that differ in their iron content and isoelectric point (pI) were isolated from iron overload rat livers by ultracentrifugation (isoferritins with high iron content and low pI) or crystallization (isoferritins with low iron content and high pI) methods. Additionally, commercial horse splenic ferritin (with a lower pI and higher iron content than rat isoferritins) was also tested. Proliferative response to Con A was decreased in a dose-dependent manner in all assays in which spleen cells were incubated with rat and horse isoferritins. However, isoferritins with higher iron contents (rat isoferritin obtained by ultracentrifugation and horse ferritin) caused a greater decrease of proliferative response at 5 and 25 μ/ml than the others. Rat and horse apoferritins showed no inhibitory effect on lymphocyte proliferative response, suggesting that the effect is due to iron probably through the damaging effect of reactive oxygen species generated by iron released by the isoferritins on lymphocyte functions.

Additionally, the role of serum ferritin level on proliferative response was studied in an experimental model of iron overload in rats. An inverse relationship between the proliferative response and serum ferritin levels was observed.

Our results suggest that the inhibitory effect of the isoferritins on lymphocyte proliferative response is due, at least partially, to the iron content of this protein and not exclusively to variation in pi as suggested by other authors. These results are in agreement with the possible immunosuppressor role of ferritin in vivo.     

Effect of Hepatic Isoferrttins from Iron Overloaded Rats on Lymphocyte Proldzerative Response: Role of Ferritin Iron Content

Iron and ferritin impair a variety of immunological functions. To evaluate the effect of ferritin iron content on rat lymphocyte proliferative response, isoferritins that differ in their iron content and isoelectric point (pI) were isolated from iron overload rat livers by ultracentrifugation (isoferritins with high iron content and low pI) or crystallization (isoferritins with low iron content and high pI) methods. Additionally, commercial horse splenic ferritin (with a lower pI and higher iron content than rat isoferritins) was also tested. Proliferative response to Con A was decreased in a dose-dependent manner in all assays in which spleen cells were incubated with rat and horse isoferritins. However, isoferritins with higher iron contents (rat isoferritin obtained by ultracentrifugation and horse ferritin) caused a greater decrease of proliferative response at 5 and 25 μ/ml than the others. Rat and horse apoferritins showed no inhibitory effect on lymphocyte proliferative response, suggesting that the effect is due to iron probably through the damaging effect of reactive oxygen species generated by iron released by the isoferritins on lymphocyte functions.

Additionally, the role of serum ferritin level on proliferative response was studied in an experimental model of iron overload in rats. An inverse relationship between the proliferative response and serum ferritin levels was observed.

Our results suggest that the inhibitory effect of the isoferritins on lymphocyte proliferative response is due, at least partially, to the iron content of this protein and not exclusively to variation in pi as suggested by other authors. These results are in agreement with the possible immunosuppressor role of ferritin in vivo.     

柚皮素下调galectin-3可缓解高糖诱导的小鼠足细胞损伤

目的 研究柚皮素联合下调半乳糖凝集素-3(galectin-3)对高糖诱导的小鼠足细胞损伤的影响.方法 小鼠足细胞给予高糖、柚皮素、galectin-3 siRNA、NF-κB信号激活剂PMA处理,MTT方法检测细胞增殖,流式细胞术检测细胞凋亡,Western印迹检测C-Caspase-3、NF-κBp65蛋白表达,硫...     

Protective Effect of Quercetin on Cadmium‐Induced Oxidative Toxicity on Germ Cells in Male Mice

Cadmium is a toxic heavy metal that is widely distributed in the environment. As a critical process, oxidative toxicity mediates the morphological and functional damages in germ cells after cadmium exposure. In this study, the protective effect of quercetin on cadmium‐induced oxidative toxicity was investigated in mouse testicular germ cells. After oral administration of cadmium chloride at 4 mg/kg body weight for 2 weeks, damages in spermatozoa occurred in the early stage of spermatogenesis. Cadmium treatment significantly decreased the testicular antioxidant system, including decreases in the glutathione (GSH) level, superoxide dismutase (SOD), and GSH peroxidase (GSH‐Px) activities. Moreover, exposure to cadmium resulted in an increase of hydrogen peroxide production and lipid peroxidation in testes. In addition, cadmium provoked germ cell apoptosis by upregulating expression of the proapoptotic proteins Bax and caspase‐3 and downregulating expression of the antiapoptotic protein Bcl‐XL. However, combined administration of a common flavonoid quercetin at 75 mg/kg body weight significantly attenuated cadmium‐induced germ cell apoptosis by suppressing the hydrogen peroxide production and lipid peroxidation in testicular tissue. Simultaneous supplementation of quercetin markedly restored the decrease in GSH level and SOD and GSH‐Px activities elicited by cadmium treatment. Additionally, quercetin protected germ cells from cadmium‐induced apoptosis by downregulating the expression of Bax and caspase‐3 and upregulating Bcl‐XL expression. These results indicate that quercetin, due to its antioxidative and antiapoptotic characters, may manifest effective protective action against cadmium‐induced oxidative toxicity in mouse testicular germ cells. Anat Rec, 2011. © 2010 Wiley‐Liss, Inc.     

山莨菪碱对过度训练大鼠急性肾损伤的保护作用

目的 研究过度训练致急性肾损伤的特点及山莨菪碱的保护作用。方法 采用大鼠游泳至力竭建立过度训练致急性肾损伤模型。将大鼠随机分为7组，即安静对照组、力竭即刻组、力竭6h组、力竭12h组、力竭24h组、山莨菪碱6h组、山莨菪碱24h组，用全自动生化仪检测各组大鼠血Cr、Ur、CK及尿γ-GT的改变；光镜观察各组肾组织结构的改变：用TUNEL法检测各组大鼠肾组织细胞凋亡，采用图像分析仪计算肾组织细胞凋亡率。结果 力竭后大鼠站立不稳，对声光刺激反应淡漠。力竭后即刻组大鼠血Ur、CK明显升高（P〈0．05），力竭6h后血Ur、CK继续升高（P〈0．01），力竭12h后血ur、Cr、CK均有所下降，尿γ-GT明显升高（P〈0．01），力竭24h后血Ur、Cr、CK均恢复到正常，尿γ-GT继续升高（P〈0．01）。光镜下力竭后即刻组大鼠肾组织结构仅见部分肾小球囊及肾小管扩张．在皮髓质交界处及髓质小血管内可见大量红细胞堆积，力竭12h大鼠可见肾小管上皮细胞刷状缘不规整，部分脱落，肾小管管腔内可见颗粒管型和透明管型，在皮髓质交界处及髓质可见大量细胞核深染，有固缩现象；力竭后即刻、6、12、24h组大鼠肾组织凋亡细胞数逐渐增多，多位于皮髓质交界处及髓质的肾小管和集合管，各组大鼠尿γ-GT与肾组织细胞凋亡率有明显相关性（P〈0．01）。应用山莨菪碱后，力竭大鼠精神状态较好，游泳时间明显延长（P〈0．01）；力竭后6h及24h血Ur、Cr、CK及尿γ-GT均明显降低（P〈0．05），肾组织结构改善，肾组织凋亡细胞数明显减少。结论 过度训练可引起急性肾损伤，肾组织细胞捌亡是其损伤的主要表现形式：山莨菪碱可提高运动能力，同时可减少肾组织细胞凋亡，进而对肾损伤起到明显的保护作用。     

几种维生素对噪声暴露小鼠肝脏糖原含量和GPT活性变化的影响

小鼠噪声暴露(3.5KH_z,103dB)60min时,肝糖原含量.饱食鼠噪声组显著低于对照组(P<0.01),事先腹腔注入Vit B_(12)、C各组高于噪声组(P<0.05),接近对照组(P>0.05);饥饿鼠噪声组.Vit B_(12)和C组均高于对照组(P<0.05和P<0.01)。肝GPT活性:饱食鼠噪卢组显著高于对照组(P<0.01),而Vit B_(12) C和E各组与对照组无差异。饥饿鼠各组间比均无差导。说明Vit B_(12)C和E均有对抗噪声引起饱食鼠肝糖原含量下降和阻碍噪声所致饱食鼠肝GPT活性上升等作用。     

Protective Effects of Indomethacin and Cyclophosphamide but Not of Infliximab on Liver Metabolic Changes Caused by Adjuvant-Induced Arthritis

In the study, indomethacin, cyclophosphamide, and infliximab were administered to adjuvant-induced arthritic rats to determine if they were able to prevent the abnormalities caused by arthritis on hepatic metabolism. The drugs were administered to arthritic rats, and at the clinical onset of arthritis (day 14 after adjuvant injection), the livers were perfused to evaluate gluconeogenesis, ureagenesis, oxygen uptake, l-lactate, pyruvate, and ammonia release from l-alanine. The effects of the drugs on body weight gain and the signs of arthritis (paw edema, appearance of secondary lesions, and weights of lymphoid tissues) were also evaluated. Cyclophosphamide could completely prevent liver metabolic changes and the inflammatory response. Indomethacin restored ureagenesis, minimized the decrease in gluconeogenesis, and exerted a partially beneficial effect on inflammatory reactions. Infliximab did not improve arthritis-induced liver metabolic alterations or inflammatory responses. These results suggest the participation of prostaglandins, but not TNF-α, on arthritis-induced liver metabolic alterations.