人参皂苷Rh_4对小鼠移植性肿瘤的抑制作用

本文阐述了三七中人参皂苷Rh4的体内抗肿瘤作用。建立S180肉瘤和肝癌H22荷瘤小鼠动物模型,将接种后的小鼠随机分为阴性对照组、阳性对照组及人参皂苷Rh4高、中、低剂量组,采用腹腔给药和灌胃给药两种方式,观察人参皂苷Rh4对小鼠移植性肿瘤的体内抑制作用以及对动物免疫器官重量的影响。结果表明:采用腹腔注射给药和灌胃给药,人参皂苷Rh4各剂量组对S180肉瘤小鼠和肝癌H22小鼠肿瘤生长均有抑制作用。与阴性对照组比较,当人参皂苷Rh4剂量为4.5 mg/kg灌胃给药时,对肉瘤S180的抑制率为47.84%(P0.01);当Rh4剂量为10.0 mg/kg腹腔注射给药时,对肝癌H22的抑制率为52.72%(P0.01)。人参皂苷Rh4对荷瘤小鼠免疫器官未见明显影响。     

藻蓝蛋白的抑瘤活性及抗氧化作用的研究

目的:观察藻蓝蛋白(phycocyanin,PC)对接种S180肉瘤小鼠的肿瘤生长及抗氧化功能的影响。方法:昆明小鼠随机分为6组(10只/组)。即模型组、PC低、中、高、最高剂量组(25,50,100,200mg/kg·d)、环磷酰胺组(CY对照组)。各组小鼠右前腋窝皮下接种S180肉瘤细胞,第二天除模型组外,其余5组分别以不同剂量的PC灌胃、CY(40mg/kg·d)腹腔注射,15天后处死,完整剥离出肿瘤,称重,计算抑瘤率;测定血浆中SOD活力、MDA含量及红细胞溶血度。结果:1.除PC低剂量组外,中、高、最高剂量组肿瘤生长比模型组显著缓慢(P<0.01),抑瘤率分别为34.8%、56.9%、68.4%、61.9%。2.PC高、最高剂量组可升高小鼠血浆中SOD酶的活力(P<0.05);PC各剂量组均能降低小鼠血浆中MDA的含量,最高剂量组与模型组比较有统计学意义(P<0.05),PC低、中、高剂量组与模型组比较有显著差异(P<0.01)。3.除PC低剂量组外,中、高、最高剂量组均能降低红细胞溶血度(P<0.05),其中高剂量组与模型组比较有显著差异(P<0.01)。结论:PC各剂量组可以抑制小鼠S180肿瘤...     

低硒心肌损伤与钾离子通道蛋白的关系研究

目的:心肌上的离子通道蛋白与心肌损伤有很大的关系,本研究通过低硒喂养对C57BL/6小鼠心肌组织损伤的影响及其对钾通道蛋白的改变。方法:将实验小鼠分为4组:对照组,低硒30天组,低硒90天组和低硒180天组。采用低硒饲料(硒含量0.0045μg/g)喂养的方法建立低硒小鼠模型,对照组给予正常饲料(硒含量0.256μg/g),与低硒组同时喂养;硒含量的测定和HE染色方法观察心肌损伤情况,Western Blotting方法检测其钾通道蛋白的表达。结果:低硒饲料喂养小鼠的心脏硒含量与正常饲料喂养的硒含量相比明显降低(P0.01);并出现轻微的心肌损伤,钾通道蛋白的表达量在低硒30天组,低硒90天组和低硒180天组下调(P0.01)。结论:成功建立低硒小鼠模型,低硒能引起小鼠心肌损伤,这种改变可能有心脏的钾通道蛋白的表达水平有关。     

大豆多糖联合环磷酰胺对S180荷瘤小鼠抗肿瘤增效作用研究

目的 从免疫学角度研究大豆多糖对环磷酰胺的减毒增效作用及其机制.方法 选用昆明种小鼠80只,随机分为阴性对照;大豆多糖(SSPS)组:50、100、200 mg/(kg· d);阳性对照:环磷酰胺(CP) 25 mg/(kg·d);大豆多糖联合环磷酰胺组:(1)CP 25 mg/(kg·d)+SSPS mg/(kg·d)、(2)CP 25 mg/(kg·d)+SSPS 100 mg/(kg·d)、(3)CP25 mg/(kg·d)+SSPS200 mg/(kg·d);0.2 mL/只,腋下接种S180,腹腔给药,连续给药10d.测定大豆多糖联合环磷酰胺对S180荷瘤小鼠瘤重、胸腺指数、脾指数的影响,ELISA法检测S180荷瘤小鼠外周血血清中细胞因子IL-2含量的影响.结果 大豆多糖能够抑制S180荷瘤小鼠的肿瘤生长,其抑瘤率分别为24.10％、35.39％和39.75％,与环磷酰胺合用后其抑瘤率为89.87％、91.91％和92.63％(P＜0.05,P＜0.01),q值0.99 ～1.00,具有协同作用;且合用后提高了环磷酰胺所致免疫低下小鼠的胸腺指数和脾指数;并促进S180荷瘤小鼠分泌IL-2.结论 大豆多糖通过增加荷瘤小鼠免疫功能而减轻环磷酰胺对机体的毒副反应,增强其抗肿瘤作用.     

低硒心肌损伤与钾离子通道蛋白的关系研究

目的：心肌上的离子通道蛋白与心肌损伤有很大的关系,本研究通过低硒喂养对C57BL／6小鼠心肌组织损伤的影响及其对钾通道蛋白的改变。方法：将实验小鼠分为4组：对照组,低硒30天组,低硒90天组和低硒180天组。采用低硒饲料（硒含量0．0045μg／g）喂养的方法建立低硒小鼠模型,对照组给予正常饲料（硒含量0．256μg/g）,与低硒组同时喂养;硒含量的测定和HE染色方法观察心肌损伤情况,WesternBlotting方法检测其钾通道蛋白的表达。结果：低硒饲料喂养小鼠的心脏硒含量与正常饲料喂养的硒含量相比明显降低（P〈0．01）;并出现轻微的心肌损伤,钾通道蛋白的表达量在低硒30天组,低硒90天组和低硒180天组下调（P〈0．01）。结论：成功建立低硒小鼠模型,低硒能引起小鼠心肌损伤,这种改变可能有心脏的钾通道蛋白的表达水平有关。     

海胆黄多糖SEP对S180的体内抑制作用

研究海胆黄多糖SEP对S180肉瘤的抑制作用及初步机制。MTT法检测SEP对体外培养的S180细胞生长的抑制作用;建立小鼠S180肉瘤模型观察SEP抗肿瘤活性;检测SEP协同ConA/LPS刺激小鼠脾淋巴细胞增殖作用;同时,考察SEP对NK细胞和杀伤性T淋巴细胞(cytotoxic T lym-phocyte,CTL)活性的影响;碳粒廓清检测SEP对小鼠单核巨噬细胞吞噬功能的影响。研究表明,海胆黄多糖SEP高中低剂量(16、8、4 mg/kg)显著抑制小鼠180实体瘤生长,增加小鼠脾指数和胸腺指数,协同ConA/LPS刺激小鼠脾淋巴细胞增殖,提高小鼠NK细胞和CTL活性,增强小鼠单核巨噬细胞的吞噬功能,通过免疫调节提高小鼠免疫功能达到抑制S180作用。     

洁丽香菇胞外粗多糖对小鼠移植性S180肉瘤的抑制作用和免疫功能调节

对洁丽香菇胞外粗多糖中多糖和蛋白含量进行测定,其中多糖含量为21.87%,蛋白含量为7.14%。通过体内实验研究该多糖对S180肉瘤的生长抑制作用。结果表明洁丽香菇胞外粗多糖高、中、低剂量组均能不同程度抑制S180 肉瘤的生长,其中高剂量组（500mg/kg）抑瘤率最高（为39.44%）,同时能显著增加胸腺指数,降低脾指数,有效改善免疫器官受损现象;中、低剂量（250mg/kg,125mg/kg）亦能抑制肿瘤生长,抑瘤率分别为30.43%和23.40%。实验中采用ELISA法对血清中各种细胞因子含量进行测定,结果表明洁丽香菇胞外粗多糖高剂量组可明显诱导血清中TNF-α、IL-12的分泌,低剂量组可诱导IFN-γ、IL-10的分泌。由此认为洁丽香菇胞外粗多糖通过恢复免疫器官功能,增加血清中TNF-α、IL-12、IFN-γ和IL-10的含量,从而达到增强细胞免疫的作用,发挥抗肿瘤活性。     

婴儿双歧杆菌对小鼠肉瘤S180的抑制作用

本文主要观察婴儿双歧杆菌(Bif. 189—3)对小鼠皮下移植肉瘤180(S180)的抑制作用。结果发现,该菌无论在S180移植前或移植后经皮下注射,均能明显抑制皮下移植S180的增长,并使带瘤鼠存活期显著延长。病理检查见实验组肿瘤坏死明显,肿瘤周围有大量炎症细胞浸润。提示该菌能非特异性增强肿瘤局部的免疫反应。     

人基质金属蛋白酶-2C端片段PEX的高效表达及活性研究

将人的PEX基因克隆到表达载体pET-15b上,构建重组工程菌BL21(DE3)/pETPEX。采用5L发酵罐补料分批培养,当菌体密度增长到OD₆₀₀为35时,用IPTG诱导,PEX蛋白形成包涵体,最终OD₆₀₀达到90,PEX的表达水平达2.2g/L。包涵体蛋白经过纯化、复性后,获得生物活性。PEX能够有效抑制HUVECs的增殖,加药96h后,20nmol/L PEX对HUVECs生长有77.9%的抑制率;PEX能阻断bFGF诱导的鸡胚尿囊膜血管生成,抑制率为85%;小鼠实验表明,当给药剂量为5mg/kg时,PEX对S180肉瘤有31.4%的抑瘤率(P<0.05)。PEX是一个有效的抑制新血管生成和肿瘤生长的蛋白质因子。     

地鳖虫蛋白提取物对小鼠S180肉瘤及鸡胚尿囊膜血管生成的抑制作用

用不同浓度的地鳖虫蛋白粗提物(0.2~0.8g/ml)作用于S180肉瘤荷瘤小鼠,观察各组的抑瘤效果及重要生理指标的差异;同时分别用地鳖虫蛋白粗提物以及经过盐析、离子交换层析、分子筛由地鳖虫蛋白粗提物分离纯化得到的活性蛋白,作用于鸡胚尿囊膜,观察它们对新生血管生成的抑制作用。结果显示,地鳖虫蛋白粗提物对S180肉瘤荷瘤小鼠有显著的抑瘤作用;蛋白质粗提物以及纯化得到的活性蛋白对鸡胚尿囊膜新生血管的生成有明显的抑制作用,纯化品的抑制活性高于粗品,且二者对鸡胚生长发育的影响较阳性对照(地塞米松组)小,差异显著。因此,地鳖虫蛋白提取物有良好的体内抑瘤作用及血管生成抑制活性。     

Natural occurrence of zearalenone in rice and soybean produced in Korea

88 rice and 75 soybean samples were collected from 8 provinces of Korea from March through September in 1988. The Fusarium mycotoxins, zearalenone was analyzed by direct competitive enzyme linked immunosorbent assay. 10.2% of rice and 9.3 % of soybean samples contained detectable zearalenone. The average levels of zearalenone of rice and soybean samples were 11.78μg/kg and 7.70μ/kg, respectively.     

Sterigmatocystin and aflatoxin B<Subscript>1</Subscript> contamination of corn,soybean meal,and formula feed in Japan

Sterigmatocystin (STC) and aflatoxin B₁ (AFB₁) were analyzed in 246 corn samples, 126 soybean meal samples, and 861 formula feed samples from the Japanese market between April 2010 and March 2015. The detection rate, the highest concentration, and the mean concentration of STC were respectively 14%, 6.4 μg/kg, and 1.2 μg/kg for corn; 14%, 1.1 μg/kg, and 0.63 μg/kg for soybean meal; and 43%, 9.1 μg/kg, and 0.97 μg/kg for formula feed. The detection rate, the highest concentration, and the mean concentration of AFB₁ were respectively 46%, 24 μg/kg, and 3.9 μg/kg for corn; 30%, 6.7 μg/kg, and 1.1 μg/kg for soybean meal; and 47%, 20 μg/kg, and 1.6 μg/kg for formula feed. A weak negative correlation between the STC and AFB₁ concentrations was observed: there was a high concentration of AFB₁ in samples that contained a lower concentration of STC and vice versa. Spearman’s rank correlation coefficient showed a weak negative correlation of ? 0.30 (p < 0.001, n = 128) for corn and ? 0.23 (p < 0.001, n = 575) for formula feed. In conclusion, no correlation was observed between the mean concentrations of STC contamination in formula feed (0.97 μg/kg) and in corn (1.2 μg/kg) and the blending rate (approximately 50%). The rate of STC contamination in the formula feed (43%) was higher than that in corn (14%). Therefore, it is likely that ingredients other than corn contribute to the contamination of formula feed with STC. In this study, regarding STC, problematic samples were not found.     

Modulation of β-amyloid precursor protein trafficking and processing by the low density lipoprotein receptor family

Selenium is an essential micronutrient that function through selenoproteins. Selenium deficiency results in lower concentrations of selenium and selenoproteins. The brain maintains it's selenium better than other tissues under low-selenium conditions. Recently, the selenium-containing protein selenoprotein P (Sepp) has been identified as a possible transporter of selenium. The targeted disruption of the selenoprotein P gene (Sepp1) results in decreased brain selenium concentration and neurological dysfunction, unless selenium intake is excessive However, the effect of selenoprotein P deficiency on the processes of memory formation and synaptic plasticity is unknown. In the present studies Sepp1(-/-) mice and wild type littermate controls (Sepp1(+/+)) fed a high-selenium diet (1 mg Se/kg) were used to characterize activity, motor coordination, and anxiety as well as hippocampus-dependent learning and memory. Normal associative learning, but disrupted spatial learning was observed in Sepp1(-/-) mice. In addition, severe alterations were observed in synaptic transmission, short-term plasticity and long-term potentiation in hippocampus area CA1 synapses of Sepp1(-/-) mice on a 1 mg Se/kg diet and Sepp1(+/+) mice fed a selenium-deficient (0 mg Se/kg) diet. Taken together, these data suggest that selenoprotein P is required for normal synaptic function, either through presence of the protein or delivery of required selenium to the CNS.     

Deletion of selenoprotein P upregulates urinary selenium excretion and depresses whole-body selenium content

Deletion of the mouse selenoprotein P gene (Sepp1) lowers selenium concentrations in many tissues. We examined selenium homeostasis in Sepp1(-/-) and Sepp1(+/+) mice to assess the mechanism of this. The liver produces and exports selenoprotein P, which transports selenium to peripheral tissues, and urinary selenium metabolites, which regulate whole-body selenium. At intakes of selenium near the nutritional requirement, Sepp1(-/-) mice had whole-body selenium concentrations 72 to 75% of Sepp1(+/+) mice. Genotype did not affect dietary intake of selenium. Sepp1(-/-) mice excreted in their urine approximately 1.5 times more selenium in relation to their whole-body selenium than did Sepp1(+/+) mice. In addition, Sepp1(-/-) mice gavaged with (75)SeO(2-)(3) excreted 1.7 to 2.4 times as much of the (75)Se in the urine as did Sepp1(+/+) mice. These findings demonstrate that deletion of selenoprotein P raises urinary excretion of selenium. When urinary small-molecule (75)Se was injected intravenously into mice, over 90% of the (75)Se appeared in the urine within 24 h, regardless of selenium status. This shows that urinary selenium is dedicated to excretion and not to utilization by tissues. Our results indicate that deletion of selenoprotein P leads to increased urinary selenium excretion. We propose that the absence of selenoprotein P synthesis in the liver makes more selenium available for urinary metabolite synthesis, increasing loss of selenium from the organism and causing the decrease in whole-body selenium and some of the decreases observed in tissues of Sepp1(-/-) mice.     

The contribution of serotonin 5-HT2C and melanocortin-4 receptors to the satiety signaling of glucagon-like peptide 1 and liraglutide, a glucagon-like peptide 1 receptor agonist, in mice

Glucagon-like peptide 1 (GLP-1), an insulinotropic gastrointestinal peptide produced mainly from intestinal endocrine L-cells, and liraglutide, a GLP-1 receptor (GLP-1R) agonist, induce satiety. The serotonin 5-HT2C receptor (5-HT2CR) and melanoroctin-4 receptor (MC4R) are involved in the regulation of food intake. Here we show that systemic administration of GLP-1 (50 and 200μg/kg)-induced anorexia was blunted in mice with a 5HT2CR null mutation, and was attenuated in mice with a heterozygous MC4R mutation. On the other hand, systemic administration of liraglutide (50 and 100μg/kg) suppressed food intake in mice lacking 5-HT2CR, mice with a heterozygous mutation of MC4R and wild-type mice matched for age. Moreover, once-daily consecutive intraperitoneal administration of liraglutide (100μg/kg) over 3days significantly suppressed daily food intake and body weight in mice with a heterozygous mutation of MC4R as well as wild-type mice. These findings suggest that GLP-1 and liraglutide induce anorexia via different central pathways.     

近红外荧光染料IR-783介导的肿瘤成像

目的评估近红外荧光染料IR-783在犬自发性肿瘤中的特异性成像。方法将IR-783染料(5μmol/kg)腹腔注射荷瘤裸鼠,通过活体成像仪检测IR-783的代谢周期,在此基础上,将IR-783染料(1.5μmol/kg)通过后肢静脉注射入自发肿瘤犬体内,5 d后手术切除肿瘤组织,分别进行荧光成像、组织切片HE染色、冰冻切片荧光观察。结果 IR-783染料注射荷瘤裸鼠后可以在肿瘤部位检测到特异性荧光,连续观察8 d,仍有较强的荧光。IR-783注射自发肿瘤犬5 d后,可在肿瘤组织中检测到特异性荧光。结论近红外荧光染料IR-783能够被肿瘤组织特异性吸收,可用于犬自发性肿瘤的特异性诊断,具有重要的临床应用前景。     

Insight into the Anti-Inflammatory Mechanism of Action of Atrial Natriuretic Peptide,a Heart Derived Peptide Hormone: Involvement of COX-2, MMPs,and NF-kB Pathways

We sought to determine the in vivo anti-inflammatory activity of atrial natriuretic peptide (ANP) using 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced acute and chronic skin inflammatory mice model. ANP treatment (2 μg/kg body weight/day/i.p. for acute and 0.5 μg/kg body weight/day/i.p. for chronic inflammatory study) was started after 30 min of TPA application. The standard drug, aspirin (ASP) (20 μg/kg body weight/day/i.p.; 10 μg/kg body weight/day/i.p., respectively) was used as a positive control for the both acute and chronic study. TPA alone treated mice exhibited a marked increase in the ear length (7 ± 0.08 vs. 13 ± 0.7 mm, p < 0.001) as well as in ear weight (80 ± 1.3 vs. 130 ± 1.5 mg, p < 0.001) as compared with control mice. Upon treatment with ANP, the increased ear length and weight were reverted back to near normal level. Similarly, ANP treatment markedly suppressed the TPA-induced chronic skin inflammatory lesion (5.7 ± 0.2 vs. 0.95 ± 0.05, p < 0.001) as compared with TPA-induced mouse skin. TPA-induced alterations in the levels of serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), total white blood cell (TWBC), serum tumor necrosis factor-α (TNF-α), natriuretic peptide receptor-A (NPR-A), cyclooxygenase-2 (COX-2), matrix metalloproteinase-2/-9 (MMP-2/-9) and nuclear factor kappa B (NF-κB) (p < 0.01, respectively) were reverted back to near normal levels. The results of the present study clearly show the in vivo anti-inflammatory activity of ANP, which is comparable with that of a standard drug, ASP. Our results suggest that ANP elicits its anti-inflammatory activity by down-regulating the expressions of NPR-A, COX-2, MMPs and NF-κB.     

Estrogen rescues heart failure through estrogen receptor Beta activation

Background

Recently, we showed that exogenous treatment with estrogen (E2) rescues pre-existing advanced heart failure (HF) in mice. Since most of the biological actions of E2 are mediated through the classical estrogen receptors alpha (ERα) and/or beta (ERβ), and both these receptors are present in the heart, we examined the role of ERα and ERβ in the rescue action of E2 against HF.

Methods

Severe HF was induced in male mice by transverse aortic constriction-induced pressure overload. Once the ejection fraction (EF) reached ~?35%, mice were treated with selective agonists for ERα (PPT, 850 μg/kg/day), ERβ (DPN, 850 μg/kg/day), or E2 (30 μg/kg/day) together with an ERβ-antagonist (PHTPP, 850 μg/kg/day) for 10 days.

Results

EF of HF mice was significantly improved to 45.3?±?2.1% with diarylpropionitrile (DPN) treatment, but not with PPT (31.1?±?2.3%). E2 failed to rescue HF in the presence of PHTPP, as there was no significant improvement in the EF at the end of the 10-day treatment (32.5?±?5.2%). The improvement of heart function in HF mice treated with ERβ agonist DPN was also associated with reduced cardiac fibrosis and increased cardiac angiogenesis, while the ERα agonist PPT had no significant effect on either cardiac fibrosis or angiogenesis. Furthermore, DPN improved hemodynamic parameters in HF mice, whereas PPT had no significant effect.

Conclusions

E2 treatment rescues pre-existing severe HF mainly through ERβ. Rescue of HF by ERβ activation is also associated with stimulation of cardiac angiogenesis, suppression of fibrosis, and restoration of hemodynamic parameters.