Endogenous estrogen status, but not genistein supplementation, modulates 7,12-dimethylbenz[a]anthracene-induced mutation in the liver cII gene of transgenic big blue rats

A growing number of studies suggest that isoflavones found in soybeans have estrogenic activity and may safely alleviate the symptoms of menopause. One of these isoflavones, genistein, is commonly used by postmenopausal women as an alternative to hormone replacement therapy. Although sex hormones have been implicated as an important risk factor for the development of hepatocellular carcinoma, there are limited data on the potential effects of the estrogens, including phytoestrogens, on chemical mutagenesis in liver. Because of the association between mutation induction and the carcinogenesis process, we investigated whether endogenous estrogen and supplemental genistein affect 7,12-dimethylbenz[a]anthracene (DMBA)-induced mutagenesis in rat liver. Intact and ovariectomized female Big Blue rats were treated with 80 mg DMBA/kg body weight. Some of the rats also received a supplement of 1,000 ppm genistein. Sixteen weeks after the carcinogen treatment, the rats were sacrificed, their livers were removed, and mutant frequencies (MFs) and types of mutations were determined in the liver cII gene. DMBA significantly increased the MFs in liver for both the intact and ovariectomized rats. While there was no significant difference in MF between the ovariectomized and intact control animals, the mutation induction by DMBA in the ovariectomized groups was significantly higher than that in the intact groups. Dietary genistein did not alter these responses. Molecular analysis of the mutants showed that DMBA induced chemical-specific types of mutations in the liver cII gene. These results suggest that endogenous ovarian hormones have an inhibitory effect on liver mutagenesis by DMBA, whereas dietary genistein does not modulate spontaneous or DMBA-induced mutagenesis in either intact or ovariectomized rats.     

Effect of fluoride and calcium on serum LPO in ovariectomized rats

目的　确定氟化物及钙对卵巢切除大鼠血清脂质过氧化物的影响。方法　 64只雌性Wistar大鼠 ,随机分为对照组 ,卵巢切除组 ,卵巢切除后单纯喂给氟组及卵巢切除后喂给氟加钙组。单纯给氟组卵巢切除后隔日喂给含氟化钠的水 ,氟离子的浓度分别是 2、4、6mg L ,氟加钙组则在喂给氟同时又加入等剂量的 90 0mg L的葡萄糖酸钙。喂养 6个月后 ,分组处死动物 ,用TBA法测定血清中的脂质过氧化物含量。结果　卵巢切除组 (OVX组 )大鼠血清中LPO含量明显高于假卵巢切除组 (Sham组 ) (P <0 .0 5 )。卵巢切除同时喂给不同剂量的氟及氟加钙组 ,即OVXF2 、OVXF4、OVXF6、OVXF2 Ca、OVXF4Ca、OVXF6Ca组大鼠血清LPO明显低于单纯卵巢切除组 (OVX组 ) (P <0 .0 1)。卵巢切除同时投给不同剂量的氟 ,即OVXF2 、OVXF4、OVXF6组与卵巢切除同时投给不同剂量的氟加钙 ,即OVXF2 Ca、OVXF4Ca、OVXF6Ca组比较大鼠血清LPO改变不明显 (P >0 .0 5 )。结论　卵巢切除骨质疏松大鼠血中LPO明显增高 ,加入不同剂量的氟及钙后改善了去势大鼠的脂质过氧化程度。提示氟化物及氟化物加钙在治疗骨质疏松方面可能提高了机体的抗氧化能力。     

去势对不同月龄雌性大鼠骨丢失的影响

为了探讨去势对不同月龄雌性大鼠体质量、骨密度、组织病理学的影响,以便选用恰当月龄的大鼠复制绝经后骨质疏松的动物模型。本研究选用3、6、12月龄的SD雌性大鼠共48只,每月龄组16只,均分成A、B两组,A组为对照组,B组为去势组。分别于术后6、12周测量体质量、腰椎和股骨的骨密度及组织病理学观察。结果发现3月龄的去势级大鼠的体质量增加尤为明显,3、6月龄大鼠的去势组较对照组在去势后6、12周骨密度均有显著性差异（P＜0．001）,组织病理学观察去势组骨小梁稀疏,皮质骨变薄,骨髓腔扩大;而12月龄的大鼠骨密度改变不显著。结论：绝经后骨质疏松模型复制大鼠的年龄是6月龄为佳,3～6月龄亦可选用,12月龄以后不适宜选择。     

Regional and selective effects of oestradiol and progesterone on NMDA and AMPA receptors in the rat brain

We investigated the effect of 10 months ovariectomy and a correction therapy, 2 weeks before the rats were killed, of oestradiol, progesterone or their combination on NMDA and AMPA receptor binding in the hippocampus, dentate gyrus, striatum, nucleus accumbens and frontal cortex of the rat brain as well as on amino acid levels in frontal cortex. NMDA and AMPA binding densities were assayed by autoradiography using, respectively, L-[3H]glutamate and [3H]AMPA; amino acid concentrations were measured by high performance liquid chromatograhy (HPLC) coupled with UV detection. Ovariectomy was without effect on NMDA and AMPA binding density in all brain regions assayed except in the hippocampal CA1 region and dentate gyrus where it decreased NMDA binding density compared to intact rats values. Oestradiol restored and increased NMDA binding density in the CA1 subfield and the dentate gyrus of ovariectomized rats but, by contrast, it decreased binding density in the striatum and in the frontal cortex while having no effect in the CA2/3 subfield of the hippocampus and in the nucleus accumbens. Oestradiol was without effect on AMPA binding density in the hippocampus and the dentate gyrus but it reduced AMPA binding density in the striatum, the frontal cortex and the nucleus accumbens. Progesterone, and oestradiol combined with progesterone, decreased NMDA but not AMPA binding density in the frontal cortex of ovariectomized rats, and they were without effect on these receptors in the other brain regions assayed. Amino acid concentrations in the frontal cortex were unchanged after ovariectomy or steroid treatments. The effect of oestradiol in the hippocampus confirmed in the present study and our novel findings in the frontal cortex, striatum and nucleus accumbens may have functional significance for schizophrenia and neurodegenerative diseases.     

雌激素干预影响腹腔脂肪积聚的实验研究

目的研究雌激素干预对雌性C57BL/6J小鼠腹腔脂肪代谢的影响.方法采用卵巢切除法造成雌激素缺乏模型,以及在动情周期正常和围绝经期的小鼠中,给以雌激素干预,观察腹腔脂肪重量的变化.3 mon 龄小鼠随机分为正常组,卵巢切除组,给雌激素 15 d 组和给雌激素 60 d 组,每组10只.小鼠摘除卵巢后饲养至 7 mon 龄处死.5和 10 mon 龄小鼠分为正常组,动情周期正常+雌激素 60 d组,围绝经期组和围绝经期+雌激素 60 d 组,每组10只,分别饲养至7和 12 mon 龄处死,检测腹腔脂肪重量.各组小鼠于处死前15和 60 d 分别皮下埋植控释雌激素(17β-雌二醇)药丸(0.18 mg/丸).结果卵巢切除组腹腔脂肪重量明显增加(P<0.05);给雌激素 15 d 组腹腔脂肪重量减轻(P＜0.05);给雌激素 60 d 组腹腔脂肪重量有明显减轻,与正常组比较无显著性差别(P>0.05).动情周期正常+雌激素组和围绝经期+雌激素组的小鼠,其腹腔脂肪重量的变化无差别.结论卵巢切除明显影响小鼠的脂肪代谢导致腹腔脂肪积聚,而雌激素干预,特别是长期应用,可以明显减少小鼠的腹腔脂肪积聚.外源性雌激素干预在动情周期正常和围绝经期对小鼠腹腔脂肪没有明显的影响.     

卵巢切除大鼠降钙素基因相关肽、乙酰胆碱和去甲肾上腺素血管效应的变化(英文)

目的　研究雌性大鼠卵巢切除和雌激素替代治疗 4个月后 ,血管活性物质对离体动脉作用的改变。方法　采用双侧卵巢切除的雌性大鼠 ,分为假手术组、去卵巢组 (8周龄切除双侧卵巢 )和雌激素替代组 (苯甲雌二醇 40 μg,sc ,每日 1次 ,卵巢切除后 1 4d开始给药至切除后 4个月 )。于给药结束时取升主动脉、胸主动脉及尾动脉 ,进行离体血管功能实验 ,观察对降钙素基因相关肽 (CGRP)、乙酰胆碱(ACh)及去甲肾上腺素 (NE)的反应。结果　卵巢切除 4个月使CGRP引起的大鼠升主动脉舒张最大效应明显降低 ,而对胸主动脉无影响 ;同时ACh对胸主动脉的舒张效应曲线明显右移 ,而对升主动脉无影响。雌激素替代治疗使上述变化反转。去卵巢组的各类动脉对NE的反应性无变化 ,而雌激素替代组的升主动脉和胸主动脉对NE引起的最大收缩效应明显降低。在尾动脉 ,去卵巢组和雌激素替代组的CGRP和NE反应性均无改变。结论　内源性雌激素可以通过多种途径调节血管反应性 ,发挥其心血管保护作用。本研究进一步提示对绝经期妇女进行激素替代治疗的重要性     

葛根素对雌激素剥夺小鼠学习记忆行为的影响

 目的研究葛根素对雌激素剥夺小鼠学习记忆功能的影响。方法卵巢摘除(Ovx)或假手术(sham)后一周,雌性小鼠给予4周的葛根素(Pur,50,100 mg·kg^-1,ip)或苯甲酸雌二醇(EB,1,5 μg·d^-1,ip)治疗。分别用Y-迷宫和水迷宫检测小鼠的分辨学习记忆和空间记忆行为:高效液相色谱分析大脑前皮层和海马组织的谷氨酸(Glu)和γ-氨基丁酸(GABA)含量。结果Ovx小鼠经50或100 mg·kg^-1Pur治疗后,在Y-迷宫达到学会标准所需训练次数分别下降11.8%和17.8%(P>0.05和P<0.05),记忆保持率分别提高23.3%和28.3%(P<0.05)。因Ovx而延长的水迷宫平台搜寻潜伏期缩短15.5%和23.8% (P<0.05)。同时,100 mg·kg^-1Pur使Ovx小鼠海马组织的Glu和GABA水平恢复正常,Glu从Ovx小鼠的(24.1±4.5)mg·g (pro)^-1回升到(27.9±3.5)mg·g(pro)^-1(P<0.05),而GABA则从(5.64±1.06)mg·g(pro)^-1回调到(4.73±0.85)mg·g(pro)^-1 (P<0.05)。结论长期Pur治疗可通过影响海马谷氨酸能和GABA能递质系统改善雌激素剥夺引起的记忆损伤,该作用可能与Pur的植物雌激素样活性有关。     

Metformin ameliorates the age‐related changes of d‐galactose administration in ovariectomized mice

Metformin (Met) has been shown to have pleiotropic effects such as neuroprotective, antioxidant, and anti‐inflammatory properties making that a potential candidate for the treatment of central nervous system (CNS) disorders. This study was designed to investigate the possible effect of Met on the d ‐galactose (d ‐gal)‐induced aging in ovariectomized mice. The female mice underwent bilateral ovariectomy. d ‐gal was administered orally at a dose of 500 mg/kg, and Met was administrated orally at doses of 1 and 10 mg/kg for 6 weeks. Anxiety‐like behavior was evaluated by the elevated plus‐maze. Physical power was assessed by vertical grid holding test and forced swimming capacity test. The brains were assessed for the level of superoxide dismutase (SOD) and brain‐derived neurotrophic factor (BDNF). Ovariectomy caused anxiety and declined the physical power as well as BDNF and SOD levels. d ‐gal administration in ovariectomized mice exacerbated these deleterious effects. Met hampered the anxiety‐like behavior and strengthened the physical power of d ‐gal‐treated ovariectomized mice. Met also increased the SOD and BDNF levels in the brains of d ‐gal‐treated ovariectomized animals. Based on the obtained results, we suggest Met administration as a novel therapeutic approach for the treatment of age‐related conditions in the absence of female sex hormones.     

Effects of antibiotics on biochemical parameters,leukocytes and Reactive Oxygen Species (ROS) in bitches after ovariectomy

It is well known that following surgical procedures, a variety of patho-physiological alterations occurs in the host, such as changes in haemodynamic, endocrine and immune functions, as well as increase in Reactive Oxygen Species (ROS). Antibiotic administration, a common practice used in surgery, affects immune functions and ROS generation. Our study was aimed to investigate the effect of five different antibiotic regimens: amoxicillin, benzylpenicillin/dihydrostreptomycin, sulfametazine/sulfamerazine/ sulfathiazole, enrofloxacin, lincomycin/spectinomycin, administered twice (2 hours before skin incision and 6 hours after the end of the surgical suture), on biochemical parameters, leukocytes and ROS concentrations, in bitches undergoing open laparotomic ovariectomy. All treated bitches recovered from surgery without developing either systemic dysfunctions, or infections at the surgical site. Mean healing time was 7?±?3 days. An increase in white blood cell count, in differential leukocyte count and in ROS concentrations occurred 24 hours after the end of surgery, followed by a gradual decrease to basal values within the fourth day after surgery. The biochemical parameters remained quite constant throughout the study. In conclusion, our results show that the above antibiotic regimens, administered only twice, are efficient in inducing an uneventful recovery after laparotomic ovariectomy and preventing the development of infections in the bitch.     

Salivary buffer effect in relation to late pregnancy and postpartum

We studied the salivary pH, buffer effect (BE), and flow rates of unstimulated and paraffin-stimulated saliva of 8 women in their late pregnancy and postpartum. Salivary samples were collected about 1 month prior to and about 2 months after delivery. In non-pregnant control women, two paraffin-stimulated salivary samples were collected 1 month apart. The salivary BE increased significantly from late pregnancy to postpartum without exception. The increase was 2.04±1.17 pH units (P < 0.001) on average. The BE increased from 4.79±1.64 (final pH) to 6.82±1.01 (final pH). This change was not due to variation in salivary flow rates, since both unstimulated and paraffin-stimulated flow rates remained unchanged. In control women the difference between the 2 BE measurements was only 0.13±0.47 pH units on average. We concluded that women with high postpartum BE values may have moderate or even low BE values in late pregnancy. In control women, individual variation was found to be low in all variables studied.