大豆异黄酮在不同的雌激素环境下对MMTV-erbB-2转基因小鼠的作用

目的 观察大豆异黄酮在不同的雌激素环境下,对MMTV-erbB-2转基因小鼠的乳腺肿瘤发生及发展的影响.方法 选取鼠龄5周的健康MMTV-erbB-2转基因雌性小鼠150只,分为对照组、低雌激素组1、低雌激素组2、高雌激素组1和高雌激素组2五组,观察各组小鼠乳腺癌的发病率和潜伏期,并采用免疫组织化学染色SP法检测各组小鼠乳腺组织中雌激素受体(ER)、孕激素受体(PR)、增殖细胞核抗原(PCNA)的表达.结果 对照组、低雌激素组1、低雌激素组2、高雌激素组1和高雌激素组2的乳腺癌发病率分别为73.3%、96.7%、30.3%、40.0%和83.3%,对照组与高雌激素组2、低雌激素组1与高雌激素组2发病率比较差异无统计学意义(P＞0.05),其他各组间比较差异有统计学意义(P＜0.05).各组小鼠乳腺癌平均潜伏期比较差异无统计学意义(P＞0.05).低雌激素组1的TEB数量与其他各组比较差异有统计学意义(P＜0.05).erbB-2表达在各组之间表达差异无统计学意义(P＞0.05).低雌激素组1、低雌激素组2、高雌激素组1和高雌激素组2与对照组乳腺ER和PR的表达比较差异无统计学意义(P＞0.05).低雌激素组1实验小鼠发生肿瘤的乳腺组织内PCNA的表达明显高于其他各组(P＜0.05).对照组与高雌激素组2,低雌激素组1与高雌激素组2比较差异有统计学意义(P＜0.05),其他各组间比较差异有统计学意义(P＜0.05).结论 大豆异黄酮在不同的雌激素环境下,对MMTV-erbB-2转基因小鼠乳腺肿瘤的发生及发展起不同的作用.低雌激素环境下大豆异黄酮可促进乳腺肿瘤的发生及发展,高雌激素环境下大豆异黄酮可抑制乳腺肿瘤的发生及发展.

Abstract：

Objective To investigate the effect of the soybean isoflavones at different estrogen environments on the pathogenesis of breast cancer in MMTV-erbB-2 transgenic mice. Methods 150 fiveweek-old MMTV-erbB-2 transgenic female mice were phosen and divided into five groups; control group,low estrogen group 1, low estrogen group 2, high estrogen group 1 and high estrogen group 2. The incidence and latent period of breast cancer were observed, and the expression of estrogen receptor (ER) ,progesterone receptor (PR), and proliferating cell nuclear antigen (PCNA) proteins was detected by using immunohistochemistry SP method. Results The incidence of breast cancer in control group, low estrogen group 1, low estrogen group 2, high estrogen group 1 and high estrogen group 2 was 73. 3% , 96. 7% ,30. 3% , 40. 0% and 83. 3% , respectively, with the difference being not significant between control group and high estrogen group 2, and between low estrogen group 1 and high estrogen group 2 (P ＞ 0. 05 ) , but with the difference being significant among the other groups (P ＜ 0. 05 ). There was significant difference in the average latent period of breast cancer among all groups (P ＞ 0. 05 ). There was significant difference in the number of TEB between low-estrogen group 1 and other groups (P ＜ 0.05). There was significant difference in the erbB-2 expression among the groups ( P ＞ 0. 05 ). There was no significant difference in the expression of breast ER and PR between control group and other groups ( P ＞ 0. 05 ). The PCNA expression in breast tumor tissue in low-estrogen group 1 was significantly higher than other groups (P ＜0. 05) , and there was significant difference in the PCNA expression between control group and high estrogen group 2, between low estrogen group 1 and high estrogen group 2 (P ＜ 0. 05). Conclusion The soybean isoflavones at different estrogen environments play different roles in the occurrence and development of MMTV-erbb-2 transgenic mouse mammary tumor. In the context of low estrogen, soybean isoflavones could even promote breast cancer formation and development. In the context of high estrogen, soybean isoflavones could inhibit breast cancer and development.     

大豆异黄酮在不同的雌激素环境下对MMTV-erbB-2转基因小鼠的作用

Objective To investigate the effect of the soybean isoflavones at different estrogen environments on the pathogenesis of breast cancer in MMTV-erbB-2 transgenic mice. Methods 150 fiveweek-old MMTV-erbB-2 transgenic female mice were phosen and divided into five groups; control group,low estrogen group 1, low estrogen group 2, high estrogen group 1 and high estrogen group 2. The incidence and latent period of breast cancer were observed, and the expression of estrogen receptor (ER) ,progesterone receptor (PR), and proliferating cell nuclear antigen (PCNA) proteins was detected by using immunohistochemistry SP method. Results The incidence of breast cancer in control group, low estrogen group 1, low estrogen group 2, high estrogen group 1 and high estrogen group 2 was 73. 3% , 96. 7% ,30. 3% , 40. 0% and 83. 3% , respectively, with the difference being not significant between control group and high estrogen group 2, and between low estrogen group 1 and high estrogen group 2 (P ＞ 0. 05 ) , but with the difference being significant among the other groups (P ＜ 0. 05 ). There was significant difference in the average latent period of breast cancer among all groups (P ＞ 0. 05 ). There was significant difference in the number of TEB between low-estrogen group 1 and other groups (P ＜ 0.05). There was significant difference in the erbB-2 expression among the groups ( P ＞ 0. 05 ). There was no significant difference in the expression of breast ER and PR between control group and other groups ( P ＞ 0. 05 ). The PCNA expression in breast tumor tissue in low-estrogen group 1 was significantly higher than other groups (P ＜0. 05) , and there was significant difference in the PCNA expression between control group and high estrogen group 2, between low estrogen group 1 and high estrogen group 2 (P ＜ 0. 05). Conclusion The soybean isoflavones at different estrogen environments play different roles in the occurrence and development of MMTV-erbb-2 transgenic mouse mammary tumor. In the context of low estrogen, soybean isoflavones could even promote breast cancer formation and development. In the context of high estrogen, soybean isoflavones could inhibit breast cancer and development.     

大豆异黄酮的类雌激素作用与预防骨质疏松研究进展

在临床医学上 ,骨质疏松的定义为 :骨质疏松症是以全身骨量减少、骨的微观结构退化为特征的、致使骨的脆性增加而易发生骨折的一种疾病[1 ] 。随着人类寿命的延长和老龄社会的到来 ,与衰老密切相关的骨质疏松症及伴发疾病的发病率逐年提高[2 ] 。目前全世界大约有 2亿人患骨质疏松 ,其发病率已跃居各种常见疾病的第 7位。老年人尤其是绝经妇女患骨质疏松的几率大于其他人群 ,主要原因是妇女进入绝经期后 ,卵巢功能减退 ,体内的雌激素水平急剧下降 ,加速了骨量丢失。有统计资料显示 ,妇女脊椎和前臂骨折发生率是男子的 6～ 1 0倍 ,65岁以上老…     

大豆异黄酮对妇女更年期综合征及骨密度的作用研究

目的拟通过人群膳食干预试验,从临床角度研究植物雌激素大豆异黄酮对妇女更年期综合征症状及主要并发症骨质疏松的预防治疗作用。方法依据纳入和排除标准,在哈尔滨地区筛选出更年期妇女90人,随机双盲法分为大豆异黄酮剂量组和安慰剂对照组,每人每天服用大豆异黄酮90mg或者安慰剂,试验期限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;生化学方法检测试食对象血清中骨代谢指标血清钙、血清磷和血清碱性磷酸酶;超声测定桡骨远端和胫骨中段的骨密度。结果大豆异黄酮组Kupperman评分中12项指标的评分均显著下降,反应骨转换的指标血清碱性磷酸酶显著下降,胫骨骨密度显著增加,均有统计学意义。讨论大豆异黄酮可有效改善妇女更年期综合征症状,增加骨密度,预防和治疗由于更年期综合征引起的骨质疏松。     

大豆异黄酮对骨代谢影响的研究进展

骨质疏松症主要特征表现为全身骨量减少和骨组织微细结构退化 ,引起骨脆性增加和骨密度降低 ,骨折危险性增加。 6 0岁以上女性骨质疏松发病率为 6 0 %～ 70 % ,雌激素缺乏是绝经后骨质疏松症的首要病因 ,雌激素替代疗法是治疗骨质疏松的首选方案 ,但这一治疗方案有一些副作用。大豆异黄酮的结构与雌激素相似 ,且具有雌激素样活性 ,流行病学调查结果显示以豆类食品为主的东方女性中骨质疏松和骨折发病率明显低于食用脂肪和肉类的西方女性[1 3] ,排除人种、遗传、锻炼、体型等因素 ,豆类制品中的异黄酮对骨代谢的影响成为目前研究热点。一、…     

大豆异黄酮对大鼠慢性移植肾肾病的防治作用

目的通过对肾移植大鼠的饮食营养干预，观察大豆异黄酮对慢性移植肾肾病的防治作用。方法选择近交系雄性Fisher（F344）大鼠作为供者，雄性Lewis（Lew）大鼠作为受者，采用显微外科技术制作肾移植模型。将受者随机分为三组，分别给予高异黄酮大豆蛋白饲料（HIS组）、低异黄酮大豆蛋白饲料（LIS组）或酪蛋白饲料（CAS组）。移植前和移植后第4、12和24周时检测血压，并收集受者的血和尿样，检测尿蛋白和血肌酐含量。24周时处死大鼠获取移植肾，行组织学和免疫组织化学检查。结果在移植后4周时，HIS组受者的尾动脉收缩压、24h尿蛋白含量和血肌酐浓度即低于LIS组和CAS组，但差异无统计学意义（P〉0．05）；移植后12周和24周时，HIS组的受者尾动脉收缩压、24h尿蛋白含量和血肌酐浓度均较LIS组和CAS组显著降低（P〈0．05）；移植后24周时，HIS组移植肾组织的间质纤维化和炎症、血管硬化、肾小球硬化和肾小管萎缩等慢性病变均较LIS组和CAS组为轻（P〈0．05）；HIS组移植肾组织中转化生长因子-β1（TGF-β1）的表达和分泌均较LIS组和CAS组为少（P〈0．05）。结论大豆异黄酮对移植肾功能和结构有保护作用，可作为一种防治慢性移植肾肾病的新方法。     

大豆异黄酮与肾脏疾病

大豆异黄酮是大豆中的一种非营养成分 ,近年来研究表明大豆异黄酮有多种生物学功能 ,能改善心血管功能 ,抗肿瘤、抗炎、改善骨质疏松 ,间接证据表明对肾脏也有良好保护作用。     

大豆异黄酮对绝经后妇女骨的影响

目的 从临床角度研究大豆异黄酮对兰州地区绝经后妇女骨的影响。方法 在兰州地区筛选出绝经后妇女60人,随机分为大豆异黄酮组(SIF)和对照组(Control),每人每天服用大豆异黄酮90mg或者同等剂量安慰剂,时间6个月。抽血检测血清碱性磷酸酶和血清钙、磷,超声测定胫骨中段骨密度（BMD）。 结果 血清碱性磷酸酶显著下降（P<0.05）,血清钙显著升高（P<0.05）,胫骨中段BMD显著升高（P<0.05）。结论 大豆异黄酮可增加绝经后妇女骨密度,减少骨丢失。因而可以预防治疗骨质疏松症。     

大豆异黄酮防治绝经后骨质疏松症的研究进展

绝经后妇女约有25%患骨质疏松症,雌激素替代疗法(ERT)虽能够有效防治绝经后骨质疏松症,但惧于其毒副作用,例如阴道出血及与增加患乳腺癌的危险性等,为许多妇女所不能接受.植物雌激素,如大豆异黄酮带有两个或三个羟基和芳香环,与雌激素结构相似,在组织中能够与雌激素受体结合,具有弱类雌激素样作用,被认为是雌激素的天然替代品,引起了人们极大的关注.     

大豆异黄酮对实验性肾病综合征疗效观察

目的 探讨大豆异黄酮对实验性肾病综合征（NS）大鼠的治疗作用。方法 32只SD大鼠随机分为4组，A、B、C组用阿霉素（ADR）按5mg/kg尾静脉注射复制NS大鼠模型，D组同时注射生理盐水。A组喂饲含异黄酮的大豆蛋白饲料，含量为3.4mg大豆异黄酮／g蛋白；B组喂饲不含异黄酮的大豆蛋白；C组喂饲酪蛋白饲料；D组为正常对照。检测大鼠血生化指标（TG、Tch、TP、Alb、HDL、LDL、Ca、Fe)、肾功能指标（BUN、Cr)，抗氧化功能指标（SOD、MDA、GSH、GSH－Px)；并作病理光镜与电镜检查；用免疫组化法检测转化生长因子（TGF）β1的阳性率。结果 与正常组相,A、B和C组都有高脂血症、低白蛋白血症、蛋白尿，血清TG、Tch明显升高，血清TP、Alb显著下降。同时，A组的TG、Tch及BUN显著低于C组。各组肾脏SOD、GSH差异无显著性意义；C组MDA高于A组，GSH－Px低于A组。电镜显示A、B、C组的屏障功能受损，足突细胞变性；A组病变较B、C组为轻。A组肾脏的TGF－β1阳性率低于B和C组。结论 大豆异黄酮对实验性NS大鼠肾脏功能和结构有保护作用。     

不同生理时期雌激素对骨量的影响

随着年龄增长,女性卵巢功能逐渐成熟、减弱、衰退,引起雌激素水平变化,导致骨量变化。特别是在青春期、孕产期、绝经期和老年期,雌激素水平会有较大变化。此时应特别关注女性的骨转换率和骨密度变化,防止骨密度下降甚至骨质疏松的发生。研究女性不同生理时期的骨量变化,有助于临床预防和治疗女性骨质疏松症,提高长期生活质量。     

Effect of blood transfusions from different H-2 donors on immune responses in mice

We studied the effect of blood transfusions (BT) from different H-2 donors on the induction of suppressor cells (SC) and of MLC inhibitory activity in serum in a drug-unmodified mouse model. Balb/c (H-2d) mice were transfused at weekly intervals with whole blood from donors of three strains using two transfusion protocols. In protocol I, blood was transfused first from C3H/HeJ (C3H) (H-2k), then C57Bl (H-2b), and then SJL (H-2s) strain mice, and in protocol II the order of blood donors was reversed. Spleen cells and serum samples were obtained from the transfused mice one and two weeks after the last BT. In both transfusion protocols, the kinetics of responses of cells from recipient transfused mice to cells from the blood donors in MLC were similar to those of cells from nontransfused mice. The peak responses of cells from transfused mice were consistently lower than those of cells from nontransfused mice. In cell-mixing experiments, radiosensitive SC capable of inhibiting responses of Balb/c mice to cells from all three blood donors in MLC could be demonstrated one week after the last transfusion in both protocols. Two weeks after the last BT, SC were demonstrable only against the first (C3H) blood donor in protocol I, and against all three blood donors in protocol II. Serum obtained one week after transfusion in protocol I inhibited responses of Balb/c mice to stimulator lymphocytes from all three blood donors in MLC. Serum obtained two weeks after BT, however, inhibited responses of recipient mice only to the first blood donor. In contrast, in protocol II, serum obtained both one and two weeks after BT did not cause inhibition of responses of cells from Balb/c mice to blood donor cells in MLC. Similar results were obtained when Balb/c mice were transfused at weekly intervals with whole blood from either C3H or from SJL mice. The data suggest that the induction of SC and/or MLC-inhibitory activity in the serum after BT is dependent on the H-2 type of the first blood donor.     

循环雌激素水平对裸鼠颗粒脂肪移植转归的影响

目的探讨循环雌激素水平对裸鼠颗粒脂肪移植转归的影响。方法取6~8周龄雌性裸鼠18只(体质量20~25 g),随机分为3组(n=6)。去势组采用卵巢切除术制备去势裸鼠模型,高雌激素组及正常雌激素组仅作相同切口进入腹膜后,不切除卵巢组织。术后高雌激素组每3天灌胃雌二醇(0.2 mg/g)1次,共持续30 d;其他两组同时间点等量PBS灌胃。术后30 d取3组裸鼠尾静脉血经ELISA检测雌二醇浓度后,将接受抽脂术的健康女性捐赠的颗粒脂肪注入裸鼠头皮下(0.3 mL/只)。脂肪移植后8周取材大体观察、称重后,制备切片行HE染色、CD31-围脂滴蛋白荧光染色、解耦联蛋白1(uncoupling protein 1,UCP1)免疫组织化学染色和雌激素受体α免疫荧光染色,测量脂肪细胞直径及脂肪组织血管密度;实时荧光定量PCR检测UCP1和雌激素受体αmRNA表达。结果实验期间裸鼠无死亡。ELISA检测显示与正常雌激素组相比,去势组雌二醇浓度明显降低,高雌激素组明显升高,差异均有统计学意义(P<0.05)。脂肪移植8周后,移植物体积从大到小依次为去势组、正常雌激素组、高雌激素组,其中去势组移植物湿重显著高于高雌激素组(P<0.05)。组织学染色显示,与正常雌激素组相比,去势组脂肪细胞增大且围脂滴蛋白表达较弱、血管密度减小,几乎不表达脂肪标记物UCP1,雌激素受体α阳性细胞减少;而高雌激素组上述观察结果与去势组相反;脂肪细胞直径、血管密度及雌激素受体α阳性细胞组间比较,差异均有统计学意义(P<0.05)。实时荧光定量PCR检测显示,与正常雌激素组相比,高雌激素组移植物UCP1和雌激素受体αmRNA相对表达量升高,而去势组均降低;组间比较差异均有统计学意义(P<0.05)。结论体内循环雌激素水平对脂肪移植的转归有显著影响。低雌激素水平导致移植物脂肪细胞肥大,高雌激素水平导致脂肪移植物中生成大量米色脂肪并伴随血管密度增大,其机制可能与升高的循环雌激素水平活化脂肪细胞上雌激素受体α相关。     

高脂饲料对不同月龄小鼠骨质疏松的影响

目的 研究高脂饲料对不同月龄小鼠骨质疏松的影响。方法 将雄性C57BL/6J小鼠随机分为6月龄正常饲料组、6月龄高脂饲料组、12月龄正常饲料组、12月龄高脂饲料组。饲养16周后处死,取小鼠血清检测血脂（TC、TG、HDL-C、LDL-C）、氧化应激和炎症（SOD、MDA、IL-6、TNF-α）以及骨代谢标志物（CTX-1、PINP）等指标的水平;取小鼠股骨经Micro-CT和HE染色分析股骨远端微观结构和骨组织形态。结果 与正常饲料组相比,各月龄高脂饲料组小鼠的体重和体脂率增加（P＜0.05）,血清中TC、TG、LDL-C水平增高（P＜0.05）,且在12月龄高脂饲料组中最高。与正常饲料组相比,Micro-CT显示各月龄高脂饲料组小鼠BV/TV、BS/TV降低（P＜0.05）,骨微结构破坏明显;HE染色显示各月龄高脂饲料组小鼠骨小梁减少。饲料相同时,12月龄组小鼠的骨量和骨小梁数目也明显低于6月龄组,且在12月龄高脂饲料组中骨量丢失最为明显。各月龄高脂饲料组小鼠血清中IL-6、TNF-α、MDA水平均较正常饲料组增高（P＜0.05）;6月龄高脂饲料组的血清CTX-1水平高于正常饲料组（P＜0.05）。结论 高脂饮食和高龄可加重小鼠氧化应激和炎症水平,损害小鼠骨健康,且高脂饮食和高龄同时存在时对鼠骨健康的损害作用更为明显。