黑米花色苷对果糖喂养大鼠胰岛素敏感性影响

目的 观察黑米花色苷提取物(AEBR)对果糖喂养大鼠胰岛素敏感性的影响,并从c-Jun氨基端激酶(JNK)活化程度的变化分析其作用机制.方法 将48只SD大鼠分成4组,设置对照,向高果糖饲料中添加8周或4周的AEBR(5 g/kg饲料),检测各组大鼠胰岛素敏感性、脂肪组织胰岛素信号转导和JNK的活化情况.结果 AEBR能够预防和改善高果糖膳食引起的大鼠胰岛索抵抗,抑制其脂肪组织内JNK的活化,显著增加胰岛素刺激后胰岛素受体底物-1(IRS-1)的酪氨酸磷酸化和葡萄糖转运体-4(GLUT4)的易位(P<0.05).结论 AEBR可能是通过抑制JNK的活化来改善果糖喂养大鼠的胰岛素敏感性.     

花色苷对ApoE基因缺陷小鼠炎症信号转导的影响

目的:探讨黑米皮(BRF)花色苷(ANTH)对ApoE基因(ApoE-/-)缺陷小鼠动脉粥样硬化(AS)斑块形成及炎症信号转导的影响。方法:将45只雄性ApoE-/-小鼠随机分为三组:阳性对照组(A组)、花色苷提取后黑米皮组(B组)和黑米皮花色苷组(C组);15只正常小鼠为阴性对照组(D组)。B组和C组分别加入黑米皮花色苷提取物及5%花色苷提取后的黑米皮,饲养20w,取血后处死动物,测定主动脉脂质斑块大小和血液各型NOS水平及NO水平,Western-blot法检测血管壁内ICAM-1及NF-κB表达。结果:C组的主动脉脂质斑块面积大小明显低于A组和B组;C组总一氧化氮合酶(tNOS)水平明显高于A组和B组;C组血清中iNOS水平略有降低,但差异不显著;C组血清cNOS和NO水平显著升高;C组COX-2mRNA、ICAM-1及NF-κB蛋白质表达下降。结论:黑米皮花色苷是黑米皮抗AS的活性成分,其作用机制与抑制NF-κB介导的炎性因子iNOS、COX-2表达及促进血管舒张因子NO生成有关。     

花色苷对高脂血症人群血脂及体内氧化应激水平的影响

目的比较纯品花色苷、黑米花色苷对高脂血症人群体内氧化应激水平的影响。方法选取高脂血症志愿者90名,按性别、年龄、收入、教育、患病服药情况匹配后随机分为黑米花色苷、纯品花色苷、安慰剂三组,每组30例,分别给予对应胶囊,每日2次,每次2粒(黑米花色苷提取物200 mg/d,纯品花色苷320 mg/d,淀粉糊精1000 mg/d),连续12w,于干预前后进行体格测量、膳食调查,并留血、尿样本检测氧化应激指标。结果干预前后各组每日膳食摄入量、营养素摄入量及供能百分比差异无统计学意义(P>0.05);黑米花色苷组干预后血清TC、TG较干预前明显降低(P<0.05);纯品花色苷组干预后血清TC、LDL较干预前明显降低(P<0.05),HDL与干预前比较明显升高(P<0.05);安慰剂组血脂各项指标干预前后无明显变化(P>0.05)。干预后纯品花色苷组的T-AOC水平较干预前以及与安慰剂组比较明显升高(P<0.05);黑米花色苷组干预后及与安慰剂组比较,差异无统计学意义(P>0.05)。干预后纯品花色苷及黑米花色组血清总SOD活性比干预前明显升高(P<0.05);亦明显高于安慰剂组(P<0.05)。三组间干预前后尿8-异前列烷浓度差异无统计学意义(P>0.05)。结论黑米花色苷与纯品花色苷具有不同程度改善高脂血症人群血脂及体内氧化应激水平的作用。     

黑米皮花色苷对动脉硬化斑块稳定性影响

目的探讨黑米皮花色苷提取物对载脂蛋白E基因缺陷(ApoE-/-)小鼠动脉粥样硬化(As)斑块稳定性及血脂的影响.方法48只ApoE-/-小鼠(C57BL/6J品系)饲喂美国营养学会1993年版啮齿类动物纯化饲料(AIN-93)30周,建立As不稳定斑块动物模型,随机分为黑米皮花色苷组、辛伐他汀组及对照组.膳食干预20周后观察无名动脉斑块形态学变化,测定不稳定斑块出现频率、相对面积和血脂水平.结果黑米皮花色苷组和辛伐他汀组与对照组相比,血清TG、TC、LDL-C、HDL-C含量显著降低,LDL-C/HDL-C比值差异无统计学意义(P＞0.05),不稳定斑块出现频率减少,斑块相对面积分别降低15.77%与14.72%(P＜0.05),但3组间血清总抗氧化能力差异无统计学意义(P＞0.05).结论黑米皮花色苷提取物能促进ApoE-/-小鼠晚期斑块的稳定性,其作用效果类似于他汀类药物,该作用可能与其改善脂代谢有关,而与抗氧化能力无关.     

不同剂量花色苷补充改善血脂异常患者的血脂水平

目的评价不同剂量的花色苷对血脂异常人群血脂相关指标的影响。方法 176例血脂异常志愿者作为研究对象(对象),按照年龄、性别随机分配进入4个组,分别为安慰剂组(n=46)、40 mg/d花色苷组(n=45)、80 mg/d花色苷组(n=42)和320mg/d花色苷组(n=43)。对象每天早餐和晚餐后各口服胶囊2粒,共服用12 w。测定干预前以及干预12w的血脂、血糖相关指标、肾功能和肝功能相关指标的水平。结果相比安慰剂组,对象经口服320mg/d花色苷提取物胶囊12 w后,LDL-C降低了6.6%(P<0.01), non-HDL-C降低了6.4%(P<0.01),TC/HDL-C降低了5.7%(P<0.01),LDL-C/HDL-C降低了7.5%(P<0.01),HDL-C升高1%(P <0.01)。经线性趋势检验:LDL-C (P=0.046)、nonHDL-C (P=0.022)、TC/HDL-C (P=0.003)、LDL-C/HDL-C (P=0.001)的降低与花色苷摄入(40~320mg/d)呈现明显的剂量相关性。其余指标未见明显变化。结论 12w随机对照干预试验表明,320mg/d花色苷的摄入可以有效改善对象的血脂水平,且花色苷在40~320 mg/d的降脂作用存在明显的剂量效应关系。花色苷提取物或富含花色苷食物的摄入或可以成为心血管疾病预防的一个重要措施。[营养学报,2020,42(2):122-129]     

越橘提取物花色苷对宫颈癌HeLa细胞的作用

目的:研究越橘提取物花色苷对宫颈癌Hela细胞的影响作用。方法:以不同浓度的越橘提取物花色苷作用于宫颈癌Hela细胞48h,采用MTT法观察越橘花色苷对Hela细胞的生长抑制作用,荧光染色观察细胞形态学改变,以流式细胞术观察DNA含量和细胞凋亡的变化情况,同时检测细胞培养上清液中IL-10、IFN-γ、TNF-α的变化。结果:Hela细胞用10、20、30、40mg/ml的越橘提取物花色苷处理48h后,随越橘花色苷浓度加大,细胞抑制率显著升高;荧光染色可见,浓染致密的颗粒状荧光,并呈现凋亡核固缩形态;流式细胞仪检测,细胞周期改变明显;IFN-γ和IL-10高于对照组,但IFN-γ与对照组有显著差别(P0.05);各组之间TNF-α变化不明显(P0.05)。结论:越橘提取物花色苷在体外对宫颈癌Hela细胞的生长有明显地抑制作用,可能与其改变细胞DNA周期、促进调亡有关。     

黑米皮花色苷提取物对动脉粥样硬化不稳定斑块作用的实验研究

目的:探讨黑米皮花色苷提取物对载脂蛋白E基因缺陷(ApoE-/-)小鼠动脉粥样硬化(atherosclerosis,AS)不稳定斑块的作用及其相关机制。方法:48只ApoE-/-小鼠(C57BL/6J品系)饲喂AIN-93基础饲料30w建立AS不稳定斑块动物模型,随机分为三组:黑米皮花色苷组(BRA)、辛伐他汀组及对照组。膳食干预20w后,应用苏木精-伊红(H-E)染色观察无名动脉处不稳定斑块变化,免疫组化法检测基质金属蛋白酶-1(matrixmetalloproteinase-1,MMP-1)和Ⅰ型胶原表达变化,RT-PCR法检测组织因子(tissuefactor,TF)mRNA表达变化。结果:BRA组和辛伐他汀组与对照组相比,无名动脉处不稳定斑块薄纤维帽和大脂核出现的频率减少,MMP-1表达下降,Ⅰ型胶原表达增加,TFmRNA表达降低。结论:黑米皮花色苷提取物对ApoE-/-小鼠AS不稳定斑块的促进作用与改变斑块的构成以及抑制TFmRNA的表达有关。     

黑米花色苷抑制人乳腺癌细胞促血管生成因子表达的机制

目的探讨黑米花色苷抑制HER-2/neu高表达人乳腺癌细胞株MDA-MB-453促血管生成因子表达的分子机制。方法以黑米花色苷和表皮细胞生长因子(EGF)单独或联合处理MDA-MB-453细胞株,Western blot检测HER-2/neu及MAPK信号通路关键蛋白ERK-1/-2的磷酸化水平改变,免疫荧光检测NF-κB p65的细胞内定位,RT-PCR检测肿瘤细胞促血管生成因子(包括VEGF、MMP-2/-9和uPA)在mRNA水平的表达变化。结果黑米花色苷能够显著抑制HER-2/neu和ERK-1/-2蛋白的磷酸化,阻止NF-Κb p65向细胞核内转位,并在mRNA水平抑制各促血管生成因子的表达。结论黑米花色苷可能通过对HER-2/neu及其下游EGFR/Ras/MAPK信号通路的阻断最终实现对肿瘤细胞促血管生成因子表达的抑制作用。     

黑米花色苷对果糖喂养大鼠的抗氧化及胰岛素增敏作用

目的观察黑米花色苷提取物(AREBR)对果糖喂养胰岛素抵抗大鼠的抗氧化及胰岛素敏感性的影响。方法将48只SD大鼠分成4组,设置对照,通过向高果糖饲料中添加8w或4w的AREBR(5g/kgdiet),观察膳食添加花色苷对大鼠血液氧化应激水平、胰岛素敏感性和葡萄糖耐量的影响。结果摄入AREBR能预防果糖引起的胰岛素抵抗;显著降低果糖喂养大鼠血液中脂质过氧化产物丙二醛(MDA)和氧化型谷胱甘肽(GSSG)的含量,改善大鼠胰岛素敏感性和葡萄糖耐量,但AREBR干预4w不能消除高胰岛素血症。结论AREBR可预防和改善果糖引起的大鼠胰岛素抵抗及葡萄糖耐量异常,这可能与其抗氧化作用有关。     

复方中药CRFC-1对花生食物过敏拮抗作用的研究

目的探讨复方中药CRFC-1在食物过敏实验性小鼠动物模型中拮抗花生诱导的食物变态反应效果及机制。方法以花生全蛋白提取物(WPE)和葡萄球菌肠毒素B(SEB)混合物致敏、激发建立食物过敏实验性小鼠动物模型,设立CRFC-1实验组和对照组。观察小鼠过敏症状,ELISA检测血清特异性IgE、IL-4、组胺水平,并做脱颗粒肥大细胞计数。结果 CRFC-1实验组小鼠过敏症状、血清特异性IgE、IL-4、组胺水平及脱颗粒肥大细胞数明显低于对照组,差异有统计学意义(P﹤0.05)。结论复方中药CRFC-1在小鼠动物模型中能够阻断WPE诱导的食物变态反应。     

Inhibitory effect of honeybee-collected pollen on mast cell degranulation in vivo and in vitro

Bee-collected pollen (bee pollen [BP]) has been used as a folk medicine for centuries against various diseases, including allergy. There is no study elucidating how BP exerts such an anti-allergic effect. Since mast cells play a central role in the pathogenesis of various allergic diseases, we investigated the effect of BP on mast cell activation elicited by the Fc immunoglobulin E (IgE) receptor (Fc epsilon RI)-mediated pathways. The in vivo effect of orally administered BP on cutaneous mast cell activation was examined by passive cutaneous anaphylaxis reaction. In vitro mast cell degranulation and IgE binding to mast cells and the status of protein tyrosine phosphorylation were examined using bone marrow-derived mast cells. Daily oral administration of BP to mice significantly reduced the cutaneous mast cell activation elicited by IgE and specific antigens. BP also reduced in vitro mast cell degranulation and tumor necrosis factor-alpha production by inhibiting IgE binding to Fc epsilon RI on mast cells. The inhibitory effect of BP on mast cell degranulation by preventing IgE binding was confirmed by the reduced levels of protein tyrosine phosphorylation, which occurred as downstream events in activated mast cells via Fc epsilon RI. These results first revealed that the anti-allergic action of BP was exerted by inhibiting the Fc epsilon RI-mediated activation of mast cells, which plays important roles, not only in the early phase, but also in the late phase of allergic reactions.     

肠易激综合征回盲部肥大细胞的实验观察

目的观察肠易激综合征(IBS)患者肠黏膜回盲部肥大细胞的分布及变化,探讨其在IBS中的可能作用。方法符合入选标准IBS患者30例,按临床症状分为腹泻型、便秘型。与15例正常人经结肠镜钳取回盲部结肠黏膜,检测肥大细胞及脱颗粒肥大细胞的数目,进行比较。结果IBS患者回盲部肥大细胞的数目增多,与正常对照组比较,有高度统计学意义,腹泻型与便秘型之间差异无统计学意义;腹泻型、便秘型患者回盲部脱颗粒肥大细胞数明显多于正常组,差异有统计学意义;便秘型与腹泻型之间比较P<0.01,有高度统计学意义。结论肠易激综合征患者回盲部肥大细胞增多,提示与IBS临床症状有相关性;腹泻型肠易激综合征回盲部脱颗粒肥大细胞增多,提示肥大细胞活化是产生IBS腹泻的原因。     

Environmental estrogens induce mast cell degranulation and enhance IgE-mediated release of allergic mediators

BACKGROUND: Prevalence and morbidity of allergic diseases have increased over the last decades. Based on the recently recognized differences in asthma prevalence between the sexes, we have examined the effect of endogenous estrogens on a key element of the allergic response. Some lipophilic pollutants have estrogen-like activities and are termed environmental estrogens. These pollutants tend to degrade slowly in the environment and to bioaccumulate and bioconcentrate in the food chain; they also have long biological half-lives. OBJECTIVES: Our goal in this study was to identify possible pathogenic roles for environmental estrogens in the development of allergic diseases. METHODS: We screened a number of environmental estrogens for their ability to modulate the release of allergic mediators from mast cells. We incubated a human mast cell line and primary mast cell cultures derived from bone marrow of wild type and estrogen receptor alpha (ER-alpha)-deficient mice with environmental estrogens with and without estradiol or IgE and allergens. We assessed degranulation of mast cells by quantifying the release of beta-hexosaminidase. RESULTS: All of the environmental estrogens tested caused rapid, dose-related release of beta-hexosaminidase from mast cells and enhanced IgE-mediated release. The combination of physiologic concentrations of 17beta-estradiol and several concentrations of environmental estrogens had additive effects on mast cell degranulation. Comparison of bone marrow mast cells from ER-alpha-sufficient and ER-alpha-deficient mice indicated that much of the effect of environmental estrogens was mediated by ER-alpha. CONCLUSIONS: Our findings suggest that estrogenic environmental pollutants might promote allergic diseases by inducing and enhancing mast cell degranulation by physiologic estrogens and exposure to allergens.     

Anticancer Activities of an Anthocyanin-Rich Extract From Black Rice Against Breast Cancer Cells In Vitro and In Vivo

Anthocyanins widely present in human diet and have a variety of health effects. This study investigates the anticancer effects of an anthocyanin-rich extract from black rice (AEBR) on breast cancer cells in vitro and in vivo. AEBR reduced the viability of breast cancer cell lines MCF-7 (ER⁺, HER2/neu^?), MDA-MB-231 (ER^?, HER2/neu^?), and MDA-MB-453 (ER^?, HER2/neu⁺) and induced apoptosis in MDA-MB-453 cells via the intrinsic pathway in vitro by activating caspase cascade, cleaving poly (ADP-ribose) polymerase (PARP), depolarizing mitochondrial membrane potential, and releasing cytochrome C. Oral administration of AEBR (100 mg/kg/day) to BALB/c nude mice bearing MDA-MB-453 cell xenografts significantly suppressed tumor growth and angiogenesis by suppressing the expression of angiogenesis factors MMP-9, MMP-2, and uPA in tumor tissue. Altogether, this study suggests the anticancer effects of AEBR against human breast cancer cells in vitro and in vivo by inducing apoptosis and suppressing angiogenesis.     

Anticancer activities of an anthocyanin-rich extract from black rice against breast cancer cells in vitro and in vivo

Anthocyanins widely present in human diet and have a variety of health effects. This study investigates the anticancer effects of an anthocyanin-rich extract from black rice (AEBR) on breast cancer cells in vitro and in vivo. AEBR reduced the viability of breast cancer cell lines MCF-7 (ER(+), HER2/neu(-)), MDA-MB-231 (ER(-), HER2/neu(-)), and MDA-MB-453 (ER(-), HER2/neu(+)) and induced apoptosis in MDA-MB-453 cells via the intrinsic pathway in vitro by activating caspase cascade, cleaving poly (ADP-ribose) polymerase (PARP), depolarizing mitochondrial membrane potential, and releasing cytochrome C. Oral administration of AEBR (100 mg/kg/day) to BALB/c nude mice bearing MDA-MB-453 cell xenografts significantly suppressed tumor growth and angiogenesis by suppressing the expression of angiogenesis factors MMP-9, MMP-2, and uPA in tumor tissue. Altogether, this study suggests the anticancer effects of AEBR against human breast cancer cells in vitro and in vivo by inducing apoptosis and suppressing angiogenesis.     

Histamine release from mast cells by terpenoid aldehydes isolated from glanded varieties of cotton

In vivo and in vitro experiments have strongly indicated that mast cell degranulation, with its release of histamine and other pharmacoactive compounds, plays a major role in the acute respiratory response of humans following inhalation of cotton textile dust. Thirteen terpenoid aldehydes isolated from the glands of the two major Gossypium species used for cotton production, stimulated significant release of histamine from mast cells at concentrations of 1 micrograms/mL. Eleven of the thirteen compounds produce significant mast cell degranulation at concentrations well below the levels of free terpenoid aldehydes that could be expected to enter the lungs during an eight hour work day under the current permissible card room standards of 200 micrograms per cubic meter. Daily mast cell degranulation, stimulated by these terpenoid aldehydes could account for many of the pathophysiological changes found in the chronic byssinotic.     

MAST CELL DEGRANULATION AND GLUCOSE HOMEOSTASIS

Lodoxamide tromethamine prevented mast cell degranulation without inhibiting hyperglycemia induced by compound 48/80. The findings suggest that this glucotropic response is independent of serotonin from mast cells.     

Electron microscopic structure of mastocytes of the airways and changes in the clinical status during steroid inhalation therapy]

The structure of epithelial mast cells obtained by bronchial biopsy from asthmatic patients reveals characteristic qualitative and quantitative features. Great amount of partly or completely depleted mast cells can be observed in active asthmatic patients, indicating the liberation of bronchoconstrictive mediators. After a two months treatment with inhalative steroid (budesonide) the process of degranulation slows down, the number of depleted mast cells decreases. Parallel with the above described phenomenon, the number of dyspneic attacks, as well as the necessity of other antiasthmatic drugs show a significant decrease. However, in this patient material, during the treatment period, airway hyperreactivity, detected by bronchial provocation, failed to show any remarkable change.     

乳腺癌与乳腺结构不良间质中肥大细胞的形态学变化

本文报道了２２例乳腺癌组织及２３例乳腺细胞不良组织间质中肥大细胞的形态、数量及分布情况，并初步探讨了乳腺癌及乳腺结构不良的类型与其间质中肥大细胞反应的关系。从数量上来看，乳腺癌组织中肥大细胞的数量与其纤维间质的多少有关，各类型癌之间肥大细胞数值的比较差异均具有显著性。在几种不同类型的乳腺结构不良标本中，肥大细胞的数量也不尽一致，而且随着乳腺结构不良程度的加重呈趋势性增加。从形态上来看，乳腺结构不良     

肥大细胞脱颗粒对子宫平滑肌肿瘤生物特征的影响

目的:探讨浸润的肥大细胞状态对子宫平滑肌肿瘤生物特征的影响。方法:选取子宫平滑肌瘤12例,子宫恶性未定平滑肌肿瘤10例,子宫平滑肌肉瘤7例,光镜观察和形态计量组织学特征、肥大细胞颗粒面积、内皮第Ⅷ因子相关抗原表达,流式细胞仪检测瘤细胞凋亡率,并分析肥大细胞颗粒面积与其它指标之间的相关关系。结果:肿瘤细胞数量为子宫平滑肌瘤最少、恶性未定平滑肌肿瘤居中、平滑肌肉瘤最多。肥大细胞颗粒面积百分比为平滑肌瘤最高,未定平滑肌肿瘤居中,平滑肌肉瘤最低;瘤细胞数与肥大细胞颗粒面积比呈负相关。平滑肌瘤内皮细胞第Ⅷ因子相关抗原阳性染色面积最低,平滑肌肉瘤最高;第Ⅷ因子相关抗原阳性染色面积与肥大细胞颗粒面积比呈负相关。平滑肌瘤瘤细胞凋亡率最低,平滑肌肉瘤最高;瘤细胞凋亡率与肥大细胞颗粒面积比呈负相关。结论:肥大细胞释放颗粒提高了子宫平滑肌肿瘤的恶性度,促进肿瘤血管的增生。