昆虫生长调节剂扑虱灵的毒性和诱变性观察

报道了新一代农药昆虫生长调节剂扑虱灵的急性、亚急性毒性和致突变性试验结果。扑虱灵SD大鼠经口急性LD_(50)雄性为6810mg/kg,雌性为5010mg/kg,经皮LD_(50)雌雄两性均>5000mg/kg。90天喂养亚慢性试验12500ppm组,动物体重增长率非常显著的降低,心、肝、肾、脾脏体比显著异常,肝肾功能和血红蛋白量有轻度改 ,2500ppm 组也出现毒性症状,据推算扑虱灵毒性阈剂量为250mg/kg,最大无作用剂量为50mg/kg。Ames和小鼠骨髓细胞微核试验结果均为阴性,提示扑虱灵无致突变性。     

N-亚硝基二乙胺(DEN)诱导SD大鼠肝癌模型的研究

目的建立与人类的肝癌发生发展过程相似的动物模型,以便研究肝癌的发生发展过程。方法取体质量120~150 g雄性SD大鼠65只,适应环境1周后随机分为实验组(50只)和对照组(15只),实验组饮用含N-亚硝基二乙(DEN)(浓度为76 ppm)(以下简称DEN)的水连续6周后停药,改自由饮水3周,再继续饮用含DEN(76 ppm)的水至20周。对照组常规自由饮水。结果病理学检查证实DEN可诱发大鼠形成肝癌,14周后成癌率为66.7%(10/15),大鼠肝癌的癌变过程大致可分为肝炎期、肝硬化期和肝癌期三个发展阶段。结论饲以76 ppm剂量DEN可诱发大鼠肝癌模型的建立,可以为我们研究大鼠肝癌的发生发展过程提供可靠的动物模型。     

雄激素受体在雌激素受体阳性乳腺癌患者中的表达及其临床意义

目的 探讨雄激素受体（AR）在雌激素受体（ER）阳性乳腺癌患者中的表达及与临床病理特征和预后的关系。方法 选取2012年10月—2013年8月锦州医科大学附属第一医院收治的ER阳性乳腺癌患者108例,采用免疫组织化学法检测AR表达水平。分析AR与患者临床病理特征及预后的关系。结果 108例ER阳性乳腺癌患者中,有72例（66.7%）AR阳性。AR阳性患者与AR阴性患者的T分期、组织学分级、PR表达比较,差异有统计学意义（P <0.05）。AR阳性的ER阳性患者总生存期（OS）和无病生存期（DFS）长于AR阴性的ER阳性患者（P <0.05）。多因素分析结果显示,AR是影响ER阳性乳腺癌患者OS［R=0.440（95% CI：0.206,0.937）］和DFS［R=0.359（95% CI：0.135,0.949）］的影响因素。结论 一定数量的ER阳性乳腺癌患者AR呈阳性,AR可以作为ER阳性乳腺癌患者的预后指标或治疗靶点。     

先天性白内障大鼠血液生化及血液流变学分析

目的测定先天性白内障大鼠血液常规、生化正常值及血液流变学变化。方法采用XS-800i血常规分析仪和OLYMPUS AV2700生化自动分析仪对185~211 g大鼠共计90只进行血液常规和生化检测及用SA-6600自动血流变测试仪对血液进行流变学的测定。结果血像检测结果是白内障与正常对照同性比较无差异显著性(P0.05);小眼白内障与正常对照同性比较红细胞宽度(RDW)间差异显著(P0.01或P0.05)。血生化检测结果是白内障大鼠与正常对照组同性间比较白蛋白(ALB)差异显著(P0.01或P0.05)雌性与对照组比较尿素(Ure)差异显著(P0.01),小眼白内障雌性与正常对照比较肌酐(Cr)差异非常显著(P0.01)。白内障、小眼白内障大鼠的红细胞是雄性的低于雌性(P0.05,P0.01)而血小板是雄性的高于雌性(P0.01),肌酐是雄性低于雌性P0.01),正常组雄雌间无差异;血液流变学各组间无差异显著性。结论白内障大鼠与正常组大鼠间某些血常规及生化指标有一定的差异,该数据为该鼠在这领域的使用提供参考。     

乳腺癌中DAX-1和AR的表达及临床意义

目的 检测乳腺癌中先天性肾上腺发育不良症的关键基因-l(DAX-1)和雄激素受体(AR)表达情况,探讨两者与乳腺癌各临床病理指标的关系。方法 采用免疫组化法检测DAX-1和AR在120例乳腺癌中的表达,并分析两者与临床各病理指标的关系。结果 120例乳腺癌中DAX-1和AR阳性表达率分别为75%(90/120)和75.83%(91/120)。DAX-1和AR的表达呈正相关(r=0.66,P<0.05)。DAX-1和AR的表达与肿瘤直径、组织学分级及ER和PR的表达状态有关(P<0.05),DAX-1的表达与TNM分期也有关(P<0.05),两者表达与患者年龄、月经状态、淋巴结转移情况均无关(P>0.05)。结论 乳腺癌中DAX-1和AR表达上调,两者的表达与肿瘤直径、组织学分级及ER和PR的表达状态有关,DAX-1表达与TNM分期也有关,乳腺癌中DAX-1和AR的高表达可能预示良好的预后,进一步研究两者对乳腺癌发生、发展的作用机制,可能对判断乳腺癌患者预后及提供新的内分泌辅助治疗生物学标志物有一定的帮助。     

先天性白内障大鼠的血压与体温的测定及相关性分析

目的 为了完善先天性白内障大鼠的背景资料,对该大鼠的血压与体重及体温进行了测定,并进行相关性分析。方法 分别取三个体重段的正常睑裂白内障大鼠、小眼白内障大鼠和正常对照SD大鼠各30只,雌雄各半,用多道生理信号采集系统进行实验。结果 三个体重段雌雄大鼠的血压间无统计学意义(P > 0.05),但随着体重的增加,血压与体重之间逐渐形成相关关系;同品系雄性大鼠标准体重与老龄大鼠血压间有统计学意义(P < 0.01)。各体重段雌雄大鼠体温有统计学意义(P < 0.01),且雄性体温均低于雌性。结论 白内障大鼠的血压、体重和体温的变化符合大鼠的生理特性,为今后该鼠的使用提供理论基础。     

香烟烟雾暴露对雄性大鼠血浆尼古丁、可替宁的影响

目的 通过对吸烟大鼠血浆尼古丁、可替宁含量的测定,探讨香烟在体内的内暴露水平。方法 清洁级SD雄性大鼠160只,随机分为2、4、6、8、12周的低、中、高染毒剂量组及对照组,每组10只。采用呼吸道静式染毒,每日染毒一次,染毒周期为2、4、6、8、12周。观察大鼠的一般毒性效应,运用气相色谱-质谱联用法检测吸烟大鼠血浆中尼古丁、可替宁的含量。结果 香烟烟雾暴露组大鼠在第3周后逐渐开始出现间歇咳嗽,腹式呼吸加剧,鼻噪音等症状,暴露时间越长,症状越明显;染毒剂量越高,染毒周期越长,大鼠体重减少越明显,与空白对照组相比,差异有显著性（P < 0.01）;大鼠血浆尼古丁的保留时间为7.5~8.5 min,随暴露时间的延长,暴露剂量的增加,大鼠血浆中尼古丁含量较空白对照组（155±56.65）ng/mL有所增加;大鼠血浆可替宁的保留时间为11.5~12.5 min;随暴露时间的延长,暴露剂量的增加,大鼠血浆中可替宁含量较空白对照组（340±41.97）ng/mL有所增加,且呈现剂量-反应关系,不同暴露周期间可替宁含量的差异有显著性（P < 0.05）,且暴露时间与暴露剂量存在交互效应（P < 0.05）。结论 香烟烟雾暴露可造成大鼠机体不同程度的损伤,大鼠血浆可替宁浓度能够有效反映香烟烟雾内暴露情况,且呈现较好的剂量-反应关系。     

Low-dose exposure to bisphenol A in combination with fructose increases expression of genes regulating angiogenesis and vascular tone in juvenile Fischer 344 rat cardiac tissue

Objectives: Epidemiological studies report associations between exposure to the high-volume chemical and endocrine disruptor bisphenol A (BPA) and cardiovascular disorders, but there is a lack of experimental studies addressing the mechanisms of action of BPA on the cardiovascular system. In the present study, effects on markers for cardiovascular function of exposure to BPA and fructose in vivo in rat cardiac tissues, and of BPA exposure in human cardiomyocytes in vitro, were investigated.

Materials: Juvenile female Fischer 344 rats were exposed to 5, 50, and 500?μg BPA/kg bodyweight/day in their drinking water from 5 to 15 weeks of age, in combination with 5% fructose. Further, cultured human cardiomyocytes were exposed to 10?nM BPA to 1?×?10⁴ nM BPA for six hours. Expression of markers for cardiovascular function and BPA target receptors was investigated using qRT-PCR.

Results: Exposure to 5?μg BPA/kg bodyweight/day plus fructose increased mRNA expression of Vegf, Vegfr2, eNos, and Ace1 in rat heart. Exposure of human cardiomyocytes to 1?×?10⁴ nM BPA increased mRNA expression of eNOS and ACE1, as well as IL-8 and NFκβ known to regulate inflammatory response.

Conclusions:. Low-dose exposure of juvenile rats to BPA and fructose induced up-regulation of expression of genes controlling angiogenesis and vascular tone in cardiac tissues. The observed effects of BPA in rat heart were in line with our present and previous studies of BPA in human endothelial cells and cardiomyocytes. These findings may aid in understanding the mechanisms of the association between BPA exposure and cardiovascular disorders reported in epidemiological studies.     

Effects of Acupuncture on Progesterone and Prolactin in Rats of Embryo Implantation Dysfunction

Objective:To investigate the effect of acupuncture on progesterone(P4) and prolactin(PRL) in rats of embryo implantation dysfunction(EID).Methods:On the first day of pregnancy,72 female Wistar rats were randomly allocated into the normal group,the EID model group,the acupuncture group and the P4 group(18 in each group).The normal group was injected sesame oil,while the other three groups were given mifepristone to establish the EID model.The acupuncture group and the P4 group were given treatment of acupuncture and P4 injection,respectively.The serum of P4 and PRL were detected by radioimmunoassay,and the mRNA and protein expressions of P4 receptor(PR) and PRL receptor(PRLR) were detected using real-time polymerase chain reaction and immunohistochemical method,respectively.Results:Compared with the normal group,the serum levels of P4 and PRL as well as the mRNA and protein expression levels of PR and PRLR in the EID model group were significantly lowered(P<0.01 or P<0.05).The above indices in the acupuncture group and the P4 group were significantly elevated compared with the EID model group(P<0.01 or P<0.05).Conclusion:Acupuncture can promote embryo implantation effectively,which might be related to the effects of acupuncture on upregulating the P4 and PRL levels in serum and the PR and PRLR expression levels in rats.     

促性腺激素释放激素激动剂对卵巢癌大鼠化疗效果的影响

目的 研究促性腺激素释放激素激动剂(GnRHa)对大鼠卵巢组织中雌激素受体α(ERa),ERB,孕激素受体(PR)和雄激素受体(AR)的表达的影响以及对环磷酰胺在卵巢癌大鼠模型中治疗效果的影响。方法 (1)80只Fischer-344大鼠分为4组,分别接受生理盐水、环磷酰胺((3TX)、GnRHa和CTX GnRHa治疗,采用免疫组化和逆转录-聚合酶链反应(RT-PCR)的方法比较各组大鼠卵巢组织中ERα,ERB,PR和AR的表达水平;(2)使用NuTu-19卵巢癌细胞系在20只Fischer-344大鼠上建立卵巢癌模型,分为3组,分别接受生理盐水、CTX和CTX GnRHa治疗,比较各组大鼠的生存时间。结果(1)4组大鼠卵巢组织中ERct、ERβ、PR、AR mRNA强度分别为0．24～0．29、1．13～1．35、0．68～0．88、1．39～1．63,免疫组化评分结果分别为4．7～5．1、15．1～15．5、8．5～9．1、17．9～19．0,各组大鼠的受体表达水平差异没有统计学意义;(2)(3TX组和联合治疗组大鼠的生存时间分别为76．0d和79．6d,两者差异没有统计学意义。结论 在大鼠模型中应用GnRHa的过程中不会改变大鼠卵巢组织中ERα、ERβ、PR、AR的表达水平,也不会影响CTX对卵巢癌大鼠模型的治疗效果。     

脑膜瘤组织中孕激素受体、雄激素受体及增殖细胞核抗原的表达

目的 :探讨脑膜瘤组织中孕激素受体 (PR)、雄激素受体 (AR)和增殖细胞核抗原 (PCNA)的表达。方法 :应用免疫组化方法检测 70例脑膜瘤PR、AR和PCNA的表达情况 ,分析它们与肿瘤组织学分级、复发及其相互关系。结果 :随组织学分级的升高 ,AR阳性细胞率 (AR LI)增高 ,Ⅰ级组与Ⅲ级组间差异有统计学意义 (P <0 .0 5 ) ;复发组AR LI高于初发组 ,差异有统计学意义 (P <0 .0 5 )。组织学分级越高 ,PR阳性细胞率 (PR LI)越低 (P <0 .0 1 ) ;复发组PR LI显著低于初发组 (P <0 .0 5 )。AR阳性组PCNA LI高于阴性组 ;PR阴性组PCNA LI高于阳性组 ,差异有统计学意义 (P <0 .0 5 )。结论 :AR表达水平与脑膜瘤组织学分级、分型及肿瘤复发有关     

子宫腺肌病与盆腔子宫内膜异位症患者性激素受体研究

目的 :探讨子宫腺肌病 ,盆腔子宫内膜异位症异位内膜中雌激素受体 (ER)、孕激受体 (PR)、雄激素受体(AR)、卵泡刺激素受体 (FSH -R)及黄体生成素受体 (LH -R)分布的差异。方法 :对子宫腺肌病 ,卵巢内膜异位症囊肿各 30例和 2 0份上述病例周期在位内膜 ,应用免疫组化S -P ,测定ER、PR、AR、FSH -R、LH -R ,并进行比较。结果 :子宫腺肌病异位内膜中AR、LH -R阳性率明显高于卵巢内膜异位囊肿异位内膜 (P <0 .0 5 ) ,而FSH -R阳性率显著低于卵巢内膜异位囊肿异位内膜 (P <0 .0 5 )。结论 :子宫腺肌病与卵巢内膜异位囊肿异位内膜AR、LH -R及FSH -R分布不同 ,可能是子宫腺肌病与卵巢内膜异位囊肿药物治疗疗效不同的原因所在。     

高脂饮食诱导大鼠生精功能障碍

目的观察给予高脂饮食对大鼠生精功能的影响。方法健康成年雄性SD大鼠20只随机分为正常对照组和高脂饮食模型组。正常对照组给予正常饮食喂养,高脂饮食模型组大鼠给予高脂饮食喂养,8周后观察其生精功能的变化。结果与正常组大鼠相比,高脂饮食组大鼠的睾丸重量/体重下降,组织学分析显示睾丸生精小管直径、生精细胞计数、间质细胞计数均下降,血清性激素水平明显异常。同时,高脂饮食组大鼠睾丸凋亡增强。结论高脂饮食可诱导大鼠生精功能障碍。     

胃癌性激素依赖性的研究

对１００例进展期胃癌临床病理资料及手术标本进行三种性激素受体（ＨＲ）检测，结果表明胃癌在发生率、年龄分布、大体及组织学类型、癌组织ＨＲ状况等方面均存在显著性别差异。推测胃癌临床病理表现的差异是由于体内各种性激素的浓度不同以及癌组织内相应受体的含量不同所致，部分胃癌可能为性激素依赖性（雌激素依赖性或雄激素依赖性），提出对胃癌进行内分泌治疗的可能性。     

Study on mechanism of Bushen Yugong Granule in treating uterine dysgenesiain treating uterine dysgenesia

Objective: To explore the therapeutic mechanism of Bushen Yugong Granule (BSYGG, a Chinese medicinal preparation) in treating infertility due to uterine dysgenesia.Methods: (1) Clinical study: Serum level of sex hormone and endometrial contents of estradial receptor (ER) and progesterone receptor (PR) in follicle period of 60 patients (the tested group) were measured and compared before and after treatment, and also compared with those of 70 normal women (the control group). (2) Experimental study: Rats were divided into the control group and 3 tested groups fed with different doses of BSYGG. Pathologic examination of pituitary, ovary and uterus of rats after BSYGG treatment were performed, and serum levels of ER, PR measured. Also, an estrogen activity experiment was conducted in some young oophorectomized rats.Results: (1) Clinical study showed the difference of serum sex hormone levels between the tested and control group was insignificant. The percentage of patients in the tested groups with endometrial ER content over ++ was lower than that in the control group (46.9 % vs 72.4 %) significantly (P < 0.05), after treatment, it rose to 65.4 %, and the change was significant, P<0.05. (2) Experimental study showed that the number of follicle, weight of uterus and serum E₂ level increased significantly after BSYGG treatment. The endometrial content of ER in the control group was 29.25±17.03%, while in the tested groups, it was 67.75 ± 24.56% to 83.00 ± 9.87% after treatment, the difference between the two groups was significant (P<0.005).Conclusion: BSYGG has an estrogen-like activity, it could increase the endometrial content of ER, enhance the effect of estrogen on uterus and promote the development of uterus, so as to elevate fertilization rate.     

伊维菌素原药对大鼠的亚急性（28天）吸入毒性研究

目的 研究伊维菌素原药对大鼠亚急性吸入毒性,求出最大无作用剂量。方法 采用SPF级Sprague-Dawley(SD)大鼠,共72只,随机分成6组,每组12只,雌雄各半。设 190、380、750 mg/m³等3个剂量组和1个溶剂对照组(0.03%吐温-80溶液),另设1个空白对照和1个附加组(750 mg/m³)。采用动式(口鼻式)吸入染毒,每天染毒1次,持续4 h,每周染毒5 d,直至28 d,附加组动物停止染毒后继续观察14 d。试验结束后,分别对动物作血液常规、生化、体重及脏器系数等测定,并进行组织病理学检查。结果 750 mg/m³剂量组雌雄大鼠在染毒后期出现被毛蓬松、呆滞、流涎、震颤等中毒反应。750 mg/m³剂量组雌鼠食物利用率下降,血清丙氨酸氨基转移酶(ALT)水平升高(P < 0.01),肝脏器系数(脏体比)升高(P < 0.05),且病理组织学检查发现部分大鼠肝细胞混浊肿胀现象;750 mg/m³剂量组雄鼠染毒第4周的体重下降,血清尿素氮(BUN)和ALT水平升高(P < 0.01),总胆固醇(CHOL)水平下降(P < 0.05)。结论 伊维菌素原药对大鼠亚急性吸入毒性试验的最大无作用剂量雌、雄性均为380 mg/m³ (4 h/d)。     

Estrogen Receptor α and β Expressions in Hypothalamus-pituitary-ovary Axis in Rats Exposed Lactationally to Soy Isoflavones and Bisphenol A

Objectives This paper aims to investigate the uterotrophic activities of lactational exposure to combination of soy isoflavones （SIF） and bisphenol A （BPA） and to examine estrogen receptor α （ERα） and estrogen receptor β （ERβ） expressions in hypothalamus-pituitary-ovary axis and uterus.Methods Maternal rats that were breeding about 8 litters were randomly divided into four groups with seven dams in each group.Dams in different treatment groups received corn oil （control）,150 mg/kg BW of SIF,150 mg/kg BW of BPA or combination of 150 mg/kg BW of SIF and 150 mg/kg BW of BPA,respectively,from postnatal day 5 to 11 （PND5-11） by gavage.On PND12 and PND70,10 female litters were killed and hypothalamus,pituitary,ovary and uterus were collected.ERα and ERβ expressions in these organs were detected with Western blotting assay.And vaginal opening time and estrus cycle were examined in animals fed for PND70.Results On PND12,the relative uterine weight of rats treated with ISF or BPA or their combination was significantly higher than that of untreated rats （P〈0.05）.But the relative uterine weight of rats in the co-exposure group was slightly lower than that in the group only exposed to SIF or BPA.On PND 70,however,the relative uterine weight in each treatment group was not statistically different from that in the control group （P〈0.05）.Vaginal opening time and estrus cycle in groups treated with SIF or BPA or their combination were similar to those in the control group （P〈0.05）.Exposure to SIF or BPA or their combination could up-regulate or down-regulate ERα and ERβ expressions in hypothalamus,pituitary,ovary and uterus on PND12 and PND70.These regulation patterns for ERα and ERβ were different in different organs at different time points.Conclusion Lactational exposure to ISF or BPA or their combination could induce uterotrophic responses in neonate rats,which disappeared in later life.But these data fail to suggest a possibility for synergic actions between SIF and BPA.It was also demonstrated that the uterotrophic effects of SIF and BPA exposure might,at least,involve modification of ERα or ERβ expressions in the hypothalamus-pituitary-ovary axis.     

雄性裸鼹鼠可育个体与不可育个体生殖系统结构与功能差异初探

目的 观察和分析雄性裸鼹鼠中可育个体和不可育个体生殖系统结构和功能的差异,初步探索雄性不可育个体不能繁育后代的原因。方法 健康雄性裸鼹鼠可育个体和不可育个体各5只,先采集一侧睾丸和附睾组织,称重后换算脏器系数;再采集另一侧睾丸组织,用中性福尔马林溶液进行固定后制备组织切片;取另一侧附睾用作精子计数、精子活动度的测定;采集血清测定血清中黄体生成素（LH）和睾酮（T）浓度。结果 与可育个体组相比较,不可育个体组的睾丸重量下降（P＜0.05）,附睾重量显著下降（P＜0.01）,且睾丸系数和附睾系数均显著下降（P＜0.01）;精子数量显著减少（P＜0.01）,精子活动度也显著减弱（P＜0.01）;血清黄体生成素和睾酮水平均显著降低（P＜0.01）;睾丸组织切片观察显示,不可育个体各级生精细胞严重脱落,排列混乱无序,支持细胞和间质细胞均有减少。 结论 雄性裸鼹鼠不可育个体生殖系统存在睾丸和附睾萎缩、生精功能下降和性激素分泌减少等现象。     

双酚A联合己烯雌酚对未成年雌性SD大鼠的雌激素效应

目的：探讨双酚A （BPA）和己烯雌酚（DES）单独和联合作用于未成年雌性SD大鼠后的雌激素效应,为进一步阐明环境雌激素（EEs）的危害机制提供依据。方法：未成年雌性SD大鼠（21d）,分为BPA （200、400和800 mg·kg^-1）组,DES （15和150 μg·kg^-1）组和BPA＋DES （100 mg·kg^-1 BPA+7.5 μg·kg^-1 DES,200 mg·kg^-1 BPA+7.5 μg·kg^-1 DES,400 mg·kg^-1 BPA+7.5μg·kg^-1 DES,400 mg·kg^-1 BPA+75.0 μg·kg^-1 DES）联合组,同时设对照组;观察各组大鼠子宫湿质量、子宫/体质量比、子宫腔内膜上皮高度、宫腔平滑肌厚度、宫腔腺体数量和成熟卵泡数量。结果：800 mg·kg^-1BPA组大鼠子宫湿质量、子宫/体质量比、子宫腔内膜上皮高度、宫腔平滑肌厚度和宫腔腺体数量较对照组明显增加（P<0.05）;15和150 μg·kg^-1DES组及各剂量联合组大鼠子宫湿质量、子宫/体质量比、子宫腔内膜上皮高度、宫腔平滑肌厚度、宫腔腺体数量和成熟卵泡数量较对照组明显增加（P<0.05）,但各剂量联合组大鼠上述指标与各剂量DES组比较差异均无统计学意义（P>0.05）。结论：BPA和DES在单独作用时均具有雌激素活性,BPA联合DES的雌激素效应表现为相加作用。