Genistein对APP695转染PC12细胞凋亡的保护作用

目的观察Genisteint（GST）对APP695转染PCI2细胞凋亡的保护作用。方法将培养的PC12细胞分为正常对照组、APP695转染组、GST干预组。采用流式细胞术检测PC12细胞凋亡率。结果APP695转染组与正常对照组比较,PC12细胞存活率明显降低,凋亡率明显升高（P〈0,01）。GST干预组与APP695转染组比较,细胞存活率显著升高,凋亡率显著降低,其中1μmol／LGST组与APP695转染纽此较,细胞凋亡率降低（P〈0．05）,5μmol／LGST组较APP695转染组细胞凋亡率则明显降低（P〈0．01）。结论GST对APP695基因转染引起的PC12细胞损伤有一定的保护作用。     

染料木素对2型糖尿病大鼠模型血糖的影响

目的研究淡豆豉中所提取的染料木素的降糖效果以及改善糖耐量的效果。方法利用链脲佐菌素注射液对喂以高脂饲料的SD大鼠进行注射,从而制作出2型糖尿病大鼠模型;随机将2型糖尿病大鼠分成4组,每组8只,即糖尿病模型组（Model）、二甲双胍干预组（MET）、染料木素低剂量干预组（Genlow）以及染料木素高剂量干预组（Genhigh）;将4组2型糖尿病大鼠按照一定要求分别处置,并测量血糖水平和糖耐量,与正常对照组（Control）进行对比;对胰腺组织HE染色进行显微观察。结果染料木素高剂量组显著降低了血糖水平达16.5左右,与糖尿病模型组及二甲双胍组比较差异具有统计学意义（P〈0.05）;改善了各时段糖耐量,与正常对照组及糖尿病模型组比较差异均具有统计学意义（P〈0.05）;对受损萎缩的胰岛B细胞有明显的修复作用,与糖尿病模型组比较具有显著性。结论染料木素可显著降低2型糖尿病大鼠的血糖水平,并改善其糖耐量,且对受损的胰岛B细胞有修复作用,使胰岛细胞表面的胰岛素受体数量增多。     

染料木黄酮通过上调血红素氧合酶-1表达减缓野百合碱诱导的大鼠肺动脉高压

目的研究染料木黄酮对野百合碱诱导的肺动脉高压大鼠肺组织血红素氧合酶-1(heme oxygenase-1,HO-1)表达的影响,探讨其减缓肺动脉高压的可能机制。方法 40只雄性SD大鼠随机分成正常对照组(n=10)、野百合碱组(n=10)、小剂量染料木黄酮治疗组(20μg/kg;n=10)、大剂量染料木黄酮治疗组(80μg/kg;n=10)。监测血流动力学变化及通过电子显微镜观察肺小动脉结构重塑,Westernblot检测肺组织HO-1的表达。结果染料木黄酮治疗组较野百合碱组大鼠平均肺动脉压降低(P<0.01),右心肥厚指数下调(P<0.01),大剂量组更显著(P<0.01)。染料木黄酮治疗组较野百合碱组大鼠肺组织HO-1表达上调(P<0.01),大剂量组更显著(P<0.01)。结论染料木黄酮能减缓野百合碱诱导的大鼠肺动脉高压,可能与上调大鼠肺组织HO-1表达有关。     

金雀异黄素抑制大鼠膀胱肿瘤作用的实验研究

目的 探讨金雀异黄素对N-甲基亚硝基脲(MNU)诱导的SD大鼠膀胱肿瘤的抑制作用.方法 将60只大鼠随机分成3组,用MNU诱导成膀胱肿瘤,实验1组和实验2组分别经腹腔注射金雀异黄素0.5、1.0 mg/kg,每两日1次;对照组用同样的方式注射生理盐水.利用统计方法和病理分级来分析金雀异黄素对MNU诱导的SD大鼠膀胱肿瘤的抑制作用.结果实验1组和实验2组与对照组比较,在体质量减少值、肿瘤个数、抑瘤率等方面,差异有统计学意义(P＜0.05);实验1组和实验2组的癌变率相比,差异有统计学意义(P＜0.05).结论 金雀异黄素对大鼠膀胱肿瘤有抑制作用,剂量越大,对肿瘤癌变抑制作用越强.     

Comparative responses of three rat strains (DA/Han,Sprague-Dawley and Wistar) to treatment with environmental estrogens

The rat uterotrophic assay is a widely used screening test for the detection of estrogenic, endocrine-disrupting chemicals. Although much attention has been paid to identifying protocol variables and reproducibility between laboratories the question whether toxicodynamic and toxicokinetic variations of different strains may affect their sensitivity to estrogenic stimuli has been rarely addressed. We have compared the estrogenic activity of the environmental chemicals genistein (GEN), bisphenol A (BPA) and p-tert-octylphenol (OCT) in DA/Han (DA), Sprague-Dawley (SD) and Wistar (WIS) rats after repeated oral application. Rats were treated per os for 3 days with different doses of these weakly estrogenic compounds and the potent reference estrogen ethinylestradiol (EE). Then uterine wet weight, thickness of the uterine epithelium, uterine gene expression of clusterin (CLU), and thickness of the vaginal epithelium were examined as parameters for estrogenic potency of the test compounds in the three strains of rats. The uterotrophic response to treatment with BPA, OCT and GEN was similar in the three strains, and allowed us to rank them as GEN being more potent than OCT, and BPA being the weakest estrogen. This was confirmed by analysis of other biological endpoints, despite some differences in the magnitude of their response among strains and to distinct compounds. For instance, the uterus wet weight response to EE treatment indicated lower sensitivity of SD rats than that of DA and WIS rats, but this was not observed for responses of the uterine or vaginal epithelium. Moreover, blood concentrations were assessed at the time of killing and related to biological responses: plasma levels of total and unconjugated BPA and GEN depended upon the dose administered and varied to some extent within treatment groups and among the three rat strains. However, there was no good correlation in the three strains between individual compound concentrations analysed 24 h after the last dose and the uterotrophic wet weights. Summarising our results, we conclude that the sensitivity of various biological endpoints can differ slightly between strains of rats. On the other hand, our data demonstrate that the choice of the rat strain does not lead to pronounced differences in the evaluation of estrogenic activities of chemicals, especially when different biological endpoints are included in the analysis.     

Effect of a novel drug-eluted balloon coated with Genistein before stent implantation in porcine coronary arteries

Background  The major drawback of stent implantation in native human coronary vessels is the occurrence of restenosis. Drug-eluting stents significantly reduce restenosis after percutaneous coronary intervention (PCI), but may be associated with persistent local inflammation involved in the restenosis mechanisms. In this setting coating coronary devices with anti-inflammatory agents represents an intriguing alternative to stent-based local drug delivery. The aim of the present study was to test in a porcine model the safety and efficacy of a novel Genistein-eluting balloon preceding coronary stenting. Design  Female piglets underwent PCI in a randomized fashion with either a Genistein-eluting or a standard balloon angioplasty, followed in all vessels by bare-metal stent implantation. Pigs were sacrificed at different time points to appraise safety (i.e. endothelialization) and efficacy (i.e. anti-inflammatory and anti-proliferative effects): 1, 4, and 6–8 weeks following PCI. Results  Overall analysis was conducted on 14 piglets. Twenty-five bare-metal stents were implanted preceded by angioplasty with a conventional balloon in 13 vessels and by the Genistein-eluted balloon in 12. No untoward effects were reported in either group. Healing and endothelialization appeared universal within 4 weeks. The Genistein-eluted balloon group disclosed a significant reduction, at four weeks from implantation, of the peri-stent inflammatory cells count (mononucleocytes 39 ± 32 Vs. 96 ± 29 per square millimetre, P = 0.019). This effect did not clearly translate into a trend towards a reduced neointimal hyperplasia at 6–8 weeks (0.13 ± 0.11 Vs. 0.14 ± 0.09, P = 0.835). Conclusion  This study provides the first in vivo demonstration of the anti-inflammatory effects of a Genistein-eluting balloon in PCI, warranting further research including the combination of a Genistein-eluting balloon with standard drug-eluting stent.     

Comparison of urodynamic effects of phytoestrogens equol,puerarin and genistein with these of estradiol 17β in ovariectomized rats

Whether urinary incontinence in the postmenopause can be prevented or delayed by estrogens is currently controversially debated. Ovariectomized (ovx) rats have been successfully used as models in the past years but plant derived substances with estrogenic effects in the lower urinary tract have not been studied so far. Therefore we compared the effects of a 3 months lasting oral administration of estradiol 17β (E2) with those of the phytoestrogens equol, genistein and puerarin. They were ovariectomized, fed with test substance containing food and then anaesthetized and catheterized with a biluminal catheter having one outlet in the bladder and another in the urethra at the level of the urethral sphincter. Urethral and bladder pressure were recorded during a 240 s period of retrograde bladder filling (2 × 0.5 ml within 30 s with 1 min filling intermission).     

Effects of genistein on hippocampal neurodegeneration of ovariectomized rats

To investigate the mechanism underlying the neurodegeneration of postmenopausal women, the effect of genistein on hippocampal neurodegeneration was investigated in ovariectomized (OVX) Sprague-Dawley rats. Three-month-old female Sprague-Dawley rats were randomly divided into four groups: sham operated; OVX only; genistein-treated OVX (OVX-genistein); and estradiol benzoate-treated OVX (OVX-EB). Genistein and EB were subcutaneously injected into rats of the OVX-genistein and OVX-EB groups, respectively, once a day from the second day after surgery. Behavioral testing began on day 31 after surgery and lasted 5 d. The activities of superoxide dismutase and content of malondialdehyde in serum, the concentration of intrasynaptosome-free calcium, membrane relative viscosity of cerebral synaptosomes, and mean optical density (MOD) of the hippocampal synaptophysin immunoreactivity product were measured, respectively, in the eighth week after surgery. It was found that the escape latency in the OVX-EB and the OVX-genistein groups was significantly lower than that in the OVX control group (p<0.05), whereas in the behavioral test, the platform-passing number was higher than in the OVX control group (p<0.05). [Ca²⁺] _i in the cerebral cortical and hippocampal synaptosome of the OVX-only group was remarkably higher than that in the other three groups (p<0.01). The hippocampal synaptosome membrane viscosity of the OVX-only group was significantly higher than that in the sham-operated, OVX-EB (p<0.05) and the OVX-genistein (p<0.01) groups. The MOD of synaptophysin immunoreactive product in the radiation layers of CA1, CA2, CA3 and the molecular layer of the dentate gyrus of the OVX-only group was significantly lower than in the sham-operated, OVX-genistein, and OVX-EB groups (p<0.01). These results suggested that genistein, which has antioxidant properties similar to estradiol, could be used as a substitute for estradiol to prevent or treat central neurodegeneration in postmenopausal women.     

Effects of phytoestrogens genistein and daidzein on progesterone and estrogen (estradiol) production of human term trophoblast cells in vitro

Objective.?Phytoestrogens are a diverse group of nonsteroidal plant compounds that occur naturally in many plants. Because they possess a ring system similar to estrogens they are able to bind on estrogen receptors alpha and beta in humans. The effects of the phytoestrogens genistein and daidzein on the production of progesterone and estrogen in isolated human term trophoblast cells in vitro were tested in this study.

Material and methods.?Cytotrophoblast cells were isolated from human term placentas. Phytoestrogens genistein and daidzein were incubated in different concentrations with trophoblast cells. Untreated cells were used as controls. After 24 h aliquots were removed and tested for progesterone and estrogen production.

Results.?The production of the steroid hormones progesterone and estrogen are influenced by phytoestrogens genistein and daidzein in human term trophoblast cells. A strong inhibition effect of both phytoestrogens tested in the production of progesterone was demonstrated. In addition, a significant stimulating effect on estrogen production by genistein and daidzein was observed.

Conclusion.?Results obtained with this study show that phytoestrogens (genistein and daidzein) sufficiently reduce progesterone production in human term trophoblast cells. Because blockade of progesterone is a possible mechanism involved in initiation of labor, we may speculate that high doses of phytoestrogens at the feto-maternal interphase could play a negative role in maintenance of pregnancy. Stimulation of estrogen production by genistein and daidzein in trophoblast cells is probably due to estrogen receptor blocking effects of both phytoestrogens. Trophoblast cells seem to compensate blocking of its estrogen receptors by higher estrogen production.