染料木素和大豆黄素对海马神经细胞H19—7增殖和神经营养因子表达的影响

目的 探讨染料木素和大豆黄素对海马神经细胞的活性和增殖作用及其可能机制.方法 H19-7/IGF-IR神经细胞在无酚红无血清DMEM培养液中培养72h后,分别加入一定浓度的染料木素、大豆黄素和雌二醇,用MTT和BrdU法分别检测细胞的活性和增殖,流式细胞术检测神经细胞周期,ELISA和RT-PCR法检测脑源性神经营养因子（BDNF）的表达.结果 处理细胞72h后,与对照组相比,20nM、200 Nm雌激素组H19-7细胞增殖分别提高了33%、36%;20 Nm、200 Nm染料木素组H19-7细胞增殖分别提高了15%、13%;200nM大豆黄素组H19-7细胞增殖分别提高了11%,差异有显著性（P＜0.05）.200nM染料木素和大豆黄素的S期细胞比例[分别为（17.64±0.43）%,（19.48±1.01）%]显著高于对照组（14.21 ± 1.75）%,差异具有显著性（P＜0.05）.染料木素和大豆黄素显著增加海马神经细胞成熟型BDNF水平及其Mrna的表达（P＜0.05）.酪氨酸激酶受体阻断剂K252a能阻断染料木素和大豆黄素的促海马神经细胞增殖作用.结论 染料木素和大豆黄素改善海马神经细胞的增殖和活性能力,其作用与促进海马细胞BDNF的表达有关.     

大豆黄素对5／6肾切除大鼠肾脏保护作用的研究

目的 探讨大豆黄素对5／6肾切除大鼠肾脏的保护作用及其机制。方法将26只雌性SD大鼠分为3组：假手术组（S组）8只,5／6肾切除模型组（M组）8只,大豆黄素治疗组（D组）10只。对M组和D组大鼠建立5／6肾切除模型,D组给予大豆黄素15mg·kg^-1·d^-1灌胃,M组给予等量生理盐水灌胃,共8周。检测各组大鼠治疗前、后24h尿蛋白定量、血肌酐（SCr）、尿素氮（BUN）、血清总蛋白（TP）和清蛋白（Alb）,观察肾组织病理学表现,检测肾组织纤维连接蛋白（FN）、Ⅳ型胶原和转化生长因子β1（TGFβ1）表达。结果与M组相比,D组24h尿蛋白量、SCr、BUN降低（P〈0．05）;肾小球硬化指数降低（P〈0．05）;肾组织FN和Ⅳ型胶原蛋白表达降低（P〈0．01）;TGF-β1mRNA及其蛋白表达降低（P〈0．05）。结论大豆黄素对5／6肾切除大鼠肾脏有保护作用,可能与其抑制肾组织TGF-β1的表达有关。     

大豆苷元对氨茶碱在大鼠体内药动学的影响

摘 要 目的:研究大豆苷元对氨茶碱在大鼠体内药动学的影响。方法: 采用HPLC方法测定大豆苷元和氨茶碱合并给药组与氨茶碱单独给药组茶碱在大鼠体内的血药浓度,比较两者的药动学参数。结果:①茶碱在0.2～20.0 μg·ml^-1浓度范围内线性关系良好,定量下限为0.2μg·ml^-1,低中高3个浓度的绝对回收率分别为（86.7±4.2）%、（90.5±3.4）%和（92.4±4.6）%,相对回收率均大于90%,日间和日内精密度RSD分别小于8.94%、9.01%;②大豆苷元和氨茶碱合并给药组和单独给药组药动学参数分别为：半衰期（t_{1/2）为(123.63±18.23)和(133.94±11.20)min,曲线下面积（AUC(0-∞)）为(1 861.03±511.23)和(2 075.41±720.96) μg·min·ml^-1,AUC(0-8)为（1 749.71±376.68）和（1 963.34±475.84）μg·min·ml^-1,达峰浓度Cmax为(10.35±0.95)和(10.23±0.82)μg·ml^-1;③合并给药组较单独给药组的主要药动学参数峰值Cmax相似,t1/2、AUC有一定降低,但差异无统计学意义。结论:大豆苷元对氨茶碱在大鼠体内的药动学无明显影响。}     

黄豆苷元片联合戊酸雌二醇片雌二醇环丙孕酮片复合包装治疗围绝经期综合征的疗效观察

目的探究黄豆苷元联合戊酸雌二醇片雌二醇环丙孕酮片复合包装治疗围绝经期综合征患者的临床效果。方法选取2016年7月—2017年7月东营市第二人民医院收治的围绝经期综合征患者140例,随机分成对照组(70例)和治疗组(70例)。对照组患者口服戊酸雌二醇片/雌二醇环丙孕酮片复合包装,1片/次,1次/d,连续治疗21 d后停药7 d为1个疗程;治疗组患者在对照组的基础上口服黄豆苷元片,1片/次,3次/d。两组患者均连续治疗3个疗程。观察两组患者临床疗效,同时比较治疗前后两组患者体内激素水平、KMI评分、子宫内膜厚度和不良反应情况。结果治疗后,对照组临床有效率为84.29%,显著低于治疗组的95.97%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者雌二醇水平显著升高(P0.05),卵泡刺激素水平显著降低(P0.05),且治疗后治疗组患者雌二醇和卵泡刺激素水平明显优于对照组(P0.05)。治疗后,两组患者KMI评分显著降低(P0.05),子宫内膜厚度显著升高(P0.05),且治疗后治疗组患者KMI评分和子宫内膜厚度明显优于对照组(P0.05)。治疗期间,对照组不良反应发生率为15.71%,明显高于治疗组的4.28%,两组比较差异具有统计学意义(P0.05)。结论黄豆苷元联合戊酸雌二醇片雌二醇环丙孕酮片复合包装治疗围绝经期综合征患者临床有效率高,不良反应率低,具有一定的临床推广应用价值。     

Genistein Inhibits Slow Component Delayed-Rectifier K Currents via a Tyrosine Kinase-Independent Pathway

In single guinea pig ventricular cells, genistein, a potent inhibitor of protein tyrosine kinase (PTK), was found to suppress the delayed-rectifier K (I_K) current. The present study was carried out to examine the underlying mechanism. Ventricular myocytes were voltage-clamped in the conventional whole-cell mode (36°C). The amplitudes of tail and steady-state (2-s pulse) currents were measured as I_K. Genistein (10–100μ ) reversibly inhibited both basal and intrapipette cAMP (1 m )-enhanced I_Kcurrents in a concentration-dependent manner with a half-maximum inhibitory concentration (IC₅₀) at 30μ . In contrast, lavendustin A (10μ ;n=5) and tyrphostin 51 (100μ ;n=5) had no effect on the currents. The inhibitory action of genistein was also seen after I_Kcurrents were activated by forskolin (500 n ) plus intrapipette orthovanadate (500μ ). The intrapipette cAMP-enhanced I_Kwas also reduced to a lesser degree by daidzein, an inactive analogue of genistein. Envelope tail and short pulse protocols revealed that genistein inhibits the slow component of I_K(I_Ks). Thus, the inhibitory action of genistein is not mediated via an inhibition of PTK but may be due to the block of I_Kschannels.     

黄豆苷元片对妇女更年期综合征及骨密度的影响

目的 探讨黄豆苷元片对更年期症状及骨质疏松症的临床治疗效果。方法 将76例更年期妇女随机分为治疗组及对照组，各38例，治疗组口服黄豆苷元片50mg／d，钙尔奇-D 600mg／d，对照组仅服钙尔奇-D600mg／d，疗程6个月，通过调查问卷形式记录Kupperman评分，评价更年期综合征症状改善情况。观察治疗前后腰椎（L2-4），股骨颈（FN），Ward三角区，大转子（GT）骨密度（BMD），骨钙素（BGP），血清碱性磷酸酶（AKP）的变化。结果 黄豆苷元片组Kupperman评分中12项指标均显著下降，与治疗前相比，各部位骨密度有较显著上升，AKP及BGP不同程度下降，均有统计学意义。结论 黄豆苷元片在治疗更年期症状及预防骨质疏松方面效果显著，有较好的应用前景。     

Pharmacokinetics of isoflavones from soy infant formula in neonatal and adult rhesus monkeys

Consumption of soy infant formula represents a unique exposure scenario in which developing children ingest a mixture of endocrine-active isoflavones along with a substantial portion of daily nutrition. Genistein and daidzein were administered as glucoside conjugates to neonatal rhesus monkeys in a fortified commercial soy formula at 5, 35, and 70 days after birth. A single gavage dosing with 10 mg/kg bw genistein and 6 mg/kg bw daidzein was chosen to represent the upper range of typical daily consumption and to facilitate complete pharmacokinetic measurements for aglycone and total isoflavones and equol. Adult monkeys were also gavaged with the same formula solution at 2.8 and 1.6 mg/kg bw genistein and daidzein, respectively, and by IV injection with isoflavone aglycones (5.2 and 3.2 mg/kg bw, respectively) to determine absolute bioavailability. Significant differences in internal exposure were observed between neonatal and adult monkeys, with higher values for dose-adjusted AUC and C_max of the active aglycone isoflavones in neonates. The magnitude and frequency of equol production by the gut microbiome were also significantly greater in adults. These findings are consistent with immaturity of metabolic and/or physiological systems in developing non-human primates that reduces total clearance of soy isoflavones from the body.     

Soy isoflavones interfere with thyroid hormone homeostasis in orchidectomized middle-aged rats

We previously reported that genistein (G) and daidzein (D) administered subcutaneously (10 mg/kg) induce changes in the angio-follicular units of the thyroid gland, reduce concentration of total thyroid hormones (TH) and increase thyrotropin (TSH) in serum of orchidectomized middle-aged (16-month-old) rats. To further investigate these effects, we now examined expression levels of the thyroglobulin (Tg), thyroperoxidase (Tpo), vascular endothelial growth factor A (Vegfa) and deiodinase type 1 (Dio 1) genes in the thyroid; in the pituitary, genes involved in TH feedback control (Tsh β, Dio 1, Dio 2, Trh receptor); and in the liver and kidney, expression of T₃-activated genes Dio 1 and Spot 14, as well as transthyretin (Ttr), by quantitative real-time PCR. We also analyzed TPO-immunopositivity and immunofluorescence of T₄ bound to Tg, determined thyroid T₄ levels and measured deiodinase enzyme activities in examined organs. Decreased expression of Tg and Tpo genes (p < 0.05) correlated with immunohistochemical staining results, and together with decreased serum total T₄ levels, indicates decreased Tg and TH synthesis following treatments with both isoflavones. However, expression of Spot 14 (p < 0.05) gene in liver and kidney was up-regulated, and liver Dio 1 expression and activity (p < 0.05) increased. At the level of pituitary, no significant change in gene expression levels, or Dio 1 and 2 enzyme activities was observed. In conclusion, both G and D impaired Tg and TH synthesis, but at the same time increased tissue availability of TH in peripheral tissues of Orx middle-aged rats.     

黄芩素和大豆黄酮对人白血病细胞系HL60体外增殖的抑制作用

目的　观察黄芩素和大豆黄酮对HL 60细胞体外增殖的抑制作用。方法　分别采用台盼蓝拒染法和MTT比色法 ,在不同条件下测定细胞增殖的抑制率。结果　MTT比色法并不适用于检测黄芩素和大豆黄酮对HL 60细胞体外增殖的影响。应用台盼蓝拒染法 ,发现黄芩素和大豆黄酮能够显著地抑制HL 60细胞的体外增殖并且呈现时效及量效关系。结论　黄芩素和大豆黄酮是两种能够明显抑制HL 60细胞体外增殖 ,具有潜在抗白血病作用的黄酮类化合物。