氯化镉对大鼠子宫内膜细胞的增殖作用

目的研究氯化镉对去卵巢大鼠子宫内膜细胞的增殖作用。方法将成年雌性大鼠去卵巢后,给予不同剂量的CdClz（0．08mg,／kg、0．40mg／kg和2．00mg／kg）连续3d,观察子宫内膜细胞有丝分裂指数和嗜银染色颗粒数。结果氯化镉中、高荆量组有丝分裂指数分别为0．81％,0．97％,均高于阴性对照组,差异有显著性（P〈0．05）。同时氯化镉高剂量组嗜银染色颗粒数为1．36～1．53,与阴性对照组相比,差异有显著性（P〈0．05）。结论氯化镉能加速细胞的分裂和增殖,因此,推断它在大鼠体内可能具有雌激素样作用。     

依普黄酮对去卵巢大鼠骨质疏松的防治作用

目的观察依普黄酮对骨质疏松的防治作用。方法60只SD雌性大鼠,随机分为6组:假手术组,阴性对照组,雌激素组和依普黄酮低、中、高剂量组。除假手术组,其余大鼠经腹腔手术切除双侧卵巢建立去卵巢大鼠骨质疏松动物模型。雌激素组和依普黄酮低、中、高剂量组分别给予17β-雌二醇10μg·kg-1·d-1,依普黄酮50、100、200mg·kg-1·d-1,持续12wk。观察各组骨密度,骨组织形态计量,骨钙、羟脯氨酸含量以及生物力学指标。结果与假手术组比较,其他各组大鼠骨密度、骨钙、骨羟脯氨酸含量均显著下降(P<0.05),股骨的力学性能有较大变化,弯曲强度和弯曲弹性模量明显降低(P<0.05)。与阴性对照组比较,依普黄酮各组大鼠骨密度、骨钙、骨羟脯氨酸含量显著提高(P<0.01),且存在一定的剂量-效应关系,同时弯曲强度和弯曲弹性模量明显增加。结论依普黄酮对去卵巢骨质疏松大鼠具有显著的骨保护效应。     

虎杖提取物对去卵巢小鼠下生殖道类雌激素样作用研究

目的研究虎杖提取物对去卵巢小鼠下生殖道的类雌激素样作用。方法昆明种小鼠40只,体质量22~26g,清洁度II级,其中30只小鼠进行动物造模后,将合格鼠随机分为3组:虎杖提取物组(Em)、乙烯雌酚组(E2)和对照组即空白基质组,另外10只小鼠不造模设为正常组。Em组和E2组,根据各鼠实际体质量精密称取虎杖提取物和乙烯雌酚,用眼科小镊子或微量加样器分别将药物注入实验鼠阴道深处,对照组同法给予相应量的空白基质栓,连续7d,于给药后5,6和7d及最后1次给药后24~48h各作l~2次阴道涂片检查,观测小鼠阴道角化细胞阳性率、乳酸杆菌菌群变化、pH值变化及阴道黏膜组织病理学分级,以此4个指标来研究虎杖提取物对去卵巢小鼠下生殖道类雌激素样作用。结果虎杖提取物对去卵巢小鼠下生殖道有一定的类雌激素样作用,与对照药一样能显著提高阴道角化细胞阳性率,显著增加阴道乳酸杆菌菌群数,恢复阴道酸性环境,改善阴道局部炎症的病理变化。结论虎杖提取物具有类雌激素样活性,有进一步研发的价值。     

大豆异黄酮对去卵巢大鼠骨密度和雌激素活性的影响(英文)

目的 :研究大豆异黄酮对去卵巢大鼠骨密度以及雌激素活性的影响。方法 :将 10～ 12月龄的雌性Wistar大鼠随机分为 6组 :假手术组 (SHAM )、切卵巢模型组 (OVX)、尼尔雌醇组 (OVX E)、小剂量异黄酮组 (L ISO)、中剂量异黄酮组 (M ISO)、大剂量异黄酮组 (H ISO) ,每组 8只。后 5组大鼠被切除双侧卵巢 ,SHAM组只被切除卵巢附近脂肪组织。L ISO ,M ISO ,H ISO分别灌胃给予 30 ,6 0 ,12 0mg·kg- 1的大豆异黄酮 ,OVX E组大鼠灌胃给予0 .2mg·kg- 1·wk- 1的尼尔雌醇 ,SHAM与OVX组以等剂量的溶剂灌胃 ,15wk后股动脉放血处死动物 ,收集血液用于血清碱性磷酸酶活性、血清雌二醇水平、血钙、血磷测定 ,分离出右侧股骨、第 2腰椎用于骨密度测量 ,测定双侧子宫重量。结果 :与SHAM组相比 ,OVX组股骨骨密度和椎骨骨密度均可见不同程度降低 (P <0 .0 5和P >0 .0 5 ) ,尼尔雌醇与异黄酮 12 0mg·kg- 1能明显升高去卵巢大鼠的股骨和椎骨骨密度 (P <0 .0 5 )。OVX组的血清碱性磷酸酶水平高于SHAM组 (P <0 .0 5 ) ,异黄酮6 0mg·kg- 1可降低去卵巢大鼠的血清碱性磷酸酶水平 (P <0 .0 5 )。OVX组的血清雌二醇水平与子宫系数明显低于SHAM组 (P <0 .0 1) ,异黄酮的不同剂量组与OVX E组的血清雌二醇水平、子宫系数都明显高于OV     

雌激素类药物对去卵巢大鼠生殖内分泌免疫的影响

目的 研究雌激素类药物对去卵巢大鼠生殖内分泌免疫系统的影响.方法 48只3～5个月龄雌性SD大鼠随机均分为8组:(1)去卵巢(OVX)组;(2)假手术(S)组;(3)去卵巢后戊酸雌二醇治疗组(A);(4)去卵巢后半量戊酸雌二醇 半量大豆异黄酮治疗组(B);(5)去卵巢后半量戊酸雌二醇 全量大豆异黄酮治疗组(C);(6)去卵巢后大豆异黄酮治疗组(D);(7)去卵巢后雷洛昔芬治疗组(E);(8)去卵巢后7-甲基异炔诺酮治疗组(F).灌服药物12周后,处死动物前腹主动脉取血,处死时留取动物子宫、肾上腺、脾脏、胸腺等生殖内分泌免疫器官.分别检测各组血清雌二醇(E2)水平和T淋巴细胞亚群 CD3 、CD4 及CD4 /CD8 表达,以及各组生殖内分泌免疫器官的重量.结果 (1)OVX组E2水平较S组明显降低(P＜0.05);A、B、C组E2水平较OVX组明显增加(P＜0.01);A组E2水平较S组明显增加(P＜0.05).(2)OVX组CD3 、CD4 及CD4 /CD8 与S组比较明显降低(P＜0.01);各用药组CD3 、CD4 值均较OVX组明显增加(P＜0.05).(3)OVX组子宫、肾上腺、脾脏、胸腺的重量较S组明显降低(P＜0.05); A、B、C、F组子宫、肾上腺、胸腺重量较OVX组明显增加(P＜0.05).结论 雌激素类药物可增强去卵巢大鼠生殖内分泌免疫系统的功能.     

雌激素类药物对去卵巢大鼠认知功能的影响

目的 研究雌激素类药物对去卵巢大鼠认知功能的影响.方法 48只3～5个月龄雌性SD大鼠(清洁级)随机分为8组:假手术组、去卵巢(OVX)组、去卵巢后7-甲基异炔诺酮治疗组、去卵巢后雷洛昔芬治疗组、去卵巢后戊酸雌二醇治疗组、去卵巢后大豆异黄酮治疗组、去卵巢后半量戊酸雌二醇+半量大豆异黄酮治疗组、去卵巢后半量戊酸雌二醇+全量大豆异黄酮治疗组,每组6只,用药3个月.做Morris水迷宫实验测定大鼠逃避潜伏期及运动策略以判断认知功能的变化,同时用RT-PCR方法检测大鼠脑部海马淀粉样蛋白前体(APP)mRNA水平.结果 OVX组逃避潜伏期明显长于假手术组.所有用药组逃避潜伏期时间明显短于OVX组;且用药组高级运动策略次数明显多于OVX组.大鼠去卵巢后.海马APP mRNA表达量明显增高,用药组及假手术组APPmRNA表达低于OVX组.结论 雌激素类药物能抵抗去卵巢大鼠认知功能的损害,且可能是通过下调去卵巢大鼠海马APP mRNA表达水平发挥作用的.     

牛奶中雌激素样物质对大鼠卵巢和子宫的影响

目的 研究牛奶中雌激素样物质对女性生殖系统的影响。方法 选用Wistar大鼠，按美国FDA方法，进行2代繁殖实验，研究牛奶中雌激素化合物对生殖系统的影响；血浆及牛奶中的IGF-1选用酶联免疫吸附(ELISA)方法。结果 动物实验研究显示，卵巢及子宫重量未发现明显的减轻或增重现象。在F0代，牛奶组和对照组大鼠2侧卵巢平均重量分别为0．39和0．37g/kg，子宫平均重量分别为2．98和2．90g/kg。在Fl代，2侧卵巢平均重量分别为0．37和0．38g/kg，牛奶组子宫平均重量为2．67g/kg，而对照组为2．74g/kg。就血浆中IGF-1而言，牛奶组与对照组相比，差异无显著性。结论 就所观察指标而言，未发现牛奶中雌激素样物质对大鼠卵巢及子宫有明显的影响。     

雌激素及植物雌激素对去卵巢大鼠乳腺组织形态和ERα亚型表达的影响

目的探讨雌激素及植物雌激素对去卵巢大鼠乳腺组织形态和ERα亚型表达的影响,并比较雌激素和植物雌激素作用的异同。方法48只Wistar大鼠随机分为8组,分别为假手术组(Sham)、去卵巢组(Ovx)、17β-雌二醇组(Ovx+Est)、17-β雌二醇+黄体酮组(Ovx+Est+Pro)、黄体酮组(Ovx+Pro)、染料木素组(Ovx+Gen)、白黎芦醇组(Ovx+Res)、根皮素组(Ovx+Phl)。对应组给药21d后处死,取乳腺组织,用蛋白免疫印迹法观察各组大鼠乳腺ERα的表达、并利用免疫组化对其形态学变化进行观察。结果乳腺组织中的ERα主要位于乳腺导管上皮细胞的胞质和胞核内。ERα在8组中均可表达,但表达量却不同。Sham与Ovx比较,Ovx组ERα表达上调(P<0·05);Ovx与Ovx+Est、Ovx+Pro、Ovx+Gen、Ovx+Res、Ovx+Phl比较,后5组ERα表达均下调(P<0·01);Ovx与Ovx+Est+Pro比较则差异无显著性(P>0·05);大鼠卵巢切除后,乳腺明显萎缩。卵巢切除大鼠皮下分别注射Gen和Phl后,乳腺结构仍呈现出卵巢切除后的表现。皮下注射Res乳腺腺泡及其上皮细胞有不同程度的增生。皮下注射Est或Est合并Pro后,乳腺组织密度增加,乳腺上皮细胞明显增生。结论植物雌激素Gen、Phl和Res与雌激素相似,可以下调去卵巢切除大鼠乳腺组织ERα的表达;Res还可促进去卵巢切除大鼠乳腺上皮细胞增生,但作用不如雌激素强。     

雌激素及植物雌激素对去卵巢大鼠子宫组织VEGF表达和形态的影响

目的比较雌激素及植物雌激素对去卵巢大鼠子宫组织VEGF和形态表达的影响。方法48只Wistar大鼠随机分为8组:假手术组(Sham)、去卵巢组(Ovx)、17β-雌二醇组(Ovx+Est)、17-β雌二醇+黄体酮组(Ovx+Est+Pro)、黄体酮组(Ovx+Pro)、染料木素组(Ovx+Gen)、白黎芦醇组(Ovx+Res)、根皮素组(Ovx+Phl)。给药21 d,用蛋白免疫印迹法观察各组子宫VEGF的表达、并用免疫组化对VEGF的表达部位和其形态学变化进行观察。结果与Sham组比较,Ovx组的VEGF表达下调;与Ovx比较,Ovx+Est和Ovx+Est+Pro两组VEGF表达均明显上调。Gen、Res和Phl对卵巢切除大鼠VEGF无影响。大鼠卵巢切除后,子宫明显萎缩且重量下降。皮下注射Est或Est合并Pro后,子宫组织密度增加,子宫被覆上皮细胞和腺体明显增生。皮下注射Gen和Phl后,子宫形态变化类似卵巢切除大鼠,注射Res可促进去卵巢大鼠子宫腺体的增生,但作用没有雌激素强。结论雌孕激素使VEGF表达明显上调;植物雌激素Res有促进腺泡增生作用。     

两种雌激素对去卵巢大鼠子宫内膜的影响

目的：探讨戊酸雌二醇和炔雌醇对去卵巢大鼠子宫内膜的作用,为绝经后妇女雌激素补充治疗提供理论依据。方法选用3月龄雌性Sprague-Dawley（ SD）大鼠40只,实验分为Sham组（假手术组）、Ovx组（去卵巢组）、A组（炔雌醇组）、B组（戊酸雌二醇组）。除Sham组外,其余各组均切除双侧卵巢建立骨质疏松动物模型。去势后4周开始A组炔雌醇（0.1 mg·kg-1·d-1）、B组戊酸雌二醇（0.4 mg·kg-1·d-1）灌胃。4组均在90 d对大鼠称重,取大鼠子宫进行称重,子宫内膜行病理切片检查。结果用药12周后各组间大鼠体重无统计学差异。 B 组子宫湿重及子宫指数明显低于A组（P〈0.05）,与Ovx组比较,无显著性差异（P〉0.05）。但A组子宫湿重及子宫指数明显升高,与Ovx组比较差异有统计学意义（P〈0.05）。两组用药组与Ovx组相比均显示子宫内膜增厚,上层单层柱状,肌层肌纤维排列规则一致,浆膜层光滑。 B组可见内膜增厚,但低于A组,两组均未见内膜增生过长、核异性和非典型增生样改变。结论戊酸雌二醇与炔雌醇用于绝经后雌激素补充治疗,虽对子宫内膜均有生长作用,但均未见过度生长及异型性改变。     

The role of biotransformation in organic mercury neurotoxicity

Although the clinical patterns of organic and inorganic mercury poisoning are very different, systemic toxicity experiments have shown that the histologicale changes in the kidneys and dorsal root ganglia neurones are identical with the 2 classes of compounds. It has been further suggested that the toxicity of organic mercurials is the result of biotransformation to inorganic mercury. To test this hypothesis, between 10^?7 and 10^?10 mol of mercuric chloride and methyl mercuric acetate were injected directly into the cerebrum of rats. The comparative size of lesions was estimated anatomically and by reference to blood brain barrier dysfunction. Inorganic lesions were only slightly larger than those produced by equimolar amounts of organic mercury. Consequently both organic and inorganic mercury must be regarded as neurotoxic in their own right. Conversion of organic to inorganic mercury certainly occurs but is not the only mechanism by which organic mercury exerts its toxicological effect.     

Toxic effects of several mercury compounds on SHand non-SH enzymes

The toxic effects of several mercury compounds on the activities of horse liver alcohol dehydrogenase (an SH-enzyme) and bovine pancreatic trypsin (a non-SH enzyme) have been studied.Non-competitive type inhibition of the alcohol dehydrogenase activity was observed, and the K_i values were calculated to be of the order of 10^?7 M, 10^?6 M and 10^?5 M for mercuric chloride, monosubstituted and disubstituted mercury compounds, respectively.On the other hand, competitive type inhibition of the activity of trypsin was found, and the K_i values were of the order of 10^?6 M and 10^?4 -10^?5 M for mercuric chloride and monosubstituted mercury compounds, respectively (the disubstituted compound could not be tested for technical reasons). These results indicate that the enzymatic activities depend on the level of substitution of mercury compounds, and the SH-enzyme was found to be more sensitive to every mercury compound tested than the non-SH enzyme.These findings may reflect the degrees of toxicity of these mercury compounds in mammalian tissues.     

The effect of methylcobalamin on the toxicity of methylmercury and mercuric chloride on nervous tissue in culture

Methylcobalamin (methyl-B₁₂, vitamin B₁₂ analog) at a concentration of 0.2·10^?5 M tended to inhibit the toxic effect of 1 and 1.5·10^?5 M methylmercuric chloride (MMC) on the development of nerve fibers, glial cells and fibroblasts from newborn rat cerebellum explants. Methyl-B₁₂ at > 1.10^?5 M significantly inhibited the toxic effect of 1 and 1.5·10^?5 M MMC. However, the protective effect of methyl-B₁₂ against the toxicity of mercuric chloride (MC) was not significant. These results are in accord with an interaction of alkyl mercurials with membranes of nervous tissue, producing the degenerative changes in the cells, since vitamin B₁₂ increases the lipid synthesis in nervous tissue. The results also indicate that the mechanism of toxic action of organic mercury is different from that of inorganic mercury.     

Chronic mercury exposure at different concentrations produces opposed vascular responses in rat aorta

Mercury chloride exposure for 30 days decreases NO bioavailability and increases oxidative stress. However, the mechanisms underlying the effects of mercury on the cardiovascular system are not completely understood, and it is not known if they are dose‐dependent or if some concentrations have no harmful effects. Thus, we investigated the effects of chronic exposure to doses low (half) and high (2.5‐fold higher) than that needed to obtain 29 nmol/L of HgCl₂ on the vascular function. Three‐month‐old male Wistar rats received intramuscular (i.m.) HgCl₂ for 30 days and were divided in three groups: lower (Low Hg); higher (High Hg); and saline was used as the control. High Hg exposure increased the contractile response to phenylephrine (PHE) in aortic rings, but Low Hg reduced it. The hyporesponsiveness in the Low Hg rats was blunted by endothelial denudation and NOS inhibition with l ‐NAME (100 μmol/L). The phosphorylated‐eNOS/eNOS protein ratio increased in the aortas of Low Hg rats. In the High Hg group, endothelial denudation increased the PHE‐induced contractions, while l ‐NAME had no effects and indomethacin (10 μmol/L), losartan (10 μmol/L) and apocynin (30 μmol/L) reduced this response. In the High Hg group, protein levels of the NADPH oxidase subunit gp91phox and cyclooxygenase‐2 increased. Our results support previous suggestions that High Hg increases oxidative stress that might activate an inflammatory cascade and the renin‐angiotensin system. However, very low Hg concentrations below the level considered safe still reduced vascular reactivity, suggesting the need for special attention to continuous exposure as a putative cause of increased cardiovascular risk.     

Cell death and cytotoxic effects in YAC-1 lymphoma cells following exposure to various forms of mercury

The effects of 1 min-4 h exposures to four Hg compounds (mercuric chloride [HgCl2], methyl mercuric chloride [CH3HgCl], p-chloromercuribenzoate [p-CMB] and thimerosal [TMS; ethylmercurithiosalicylate]) on cell death, microtubules, actin, CD3 receptor expression, protein tyrosine phosphorylation (PTyr-P) and intracellular calcium ([Ca2+]i) levels were investigated in YAC-1 lymphoma cells using flow cytometry. YOPRO-1 (YP) and propidium iodide (PI) dye uptake indicated all forms of Hg tested were toxic at concentrations ranging from 25.8-48.4 microM, with two distinct patterns of effects. Early apoptosis was prolonged for CH3HgCl- and TMS-treated cells, with more than 50% remaining YP+/PI- after 4h. Both CH3HgCl and TMS induced complete loss of beta-tubulin fluorescence, indicative of microtubule depolymerization and inhibition of tubulin synthesis and/or beta-tubulin degradation, while F-actin fluorescence diminished to a lesser degree and only after loss beta-tubulin. CH3HgCl and TMS induced an almost immediate two-fold increase in CD3 fluorescence, with levels returning to baseline within minutes. With continued exposure, CD3 fluorescence was reduced to approximately 50% of baseline values. Both compounds also increased PTyr-P two- to three-fold immediately, with levels returning to baseline at 4h. Similarly, two- to three-fold increases in [Ca2+]i were noted after 1 min exposure. [Ca2+]i increased progressively, reaching levels five- to eight-fold greater than control values. In contrast, dye uptake was delayed with HgCl2 and p-CMB, although cell death proceeded rapidly, with almost all non-viable cells being late apoptotic (YP+/PI+) by 4h. p-CMB produced early reductions in F-actin, and after 4h, complete loss of F-actin with only partial reduction of total beta-tubulin was seen with both p-CMB and HgCl2. HgCl2 reduced CD3 expression and PTyr-P slightly within minutes, while p-CMB produced similar effects on CD3 only at 4h, at which time PTyr-P was increased two- to three-fold. Both compounds increased [Ca2+]i within minutes, though levels remained under twice the baseline concentration after 15 min exposure. With continued exposure, [Ca2+]i increased to levels two- to five-fold greater than control values. These findings indicate the two groups of Hg compounds may induce cell death by distinct pathways, reflecting interactions with different cellular targets leading to cell death.     

蛇床子总香豆素对去卵巢骨骼的影响(英文)

蛇床子总香豆素(TCFC)5g·kg~(-1)·d~(-1)ig,每周6次,持续7wk。不脱钙骨制片测量。结果:(1)去卵巢喂水模型组胫骨骨小梁明显减少(-44％),出现骨吸收大于形成的骨高转化率。(2)用TCFC治疗的去卵巢组与(1)比胫骨骨小梁的面积增加( 41％),并降低骨高转化率的指标使基本接近对照组(除类骨质外,但矿化延迟时间不变)。本文提示TCFC可能防止绝经早期由骨高转化率引起的骨丢失。     

Protective effect of Fragaria ananassa methanolic extract on cadmium chloride (CdCl2)-induced hepatotoxicity in rats

This study investigated the protective effect of Fragaria ananassa methanolic extract on cadmium chloride (CdCl₂)-induced hepatotoxicity in rats. CdCl₂ was intraperitoneally injected at a dose of 6.5?mg/kg of body weight for 5 d with or without methanol extract of Fragaria ananassa (250?mg/kg). The hepatic cadmium concentration, lipid peroxidation, nitric oxide, glutathione (GSH) content, and antioxidant enzyme activities, including superoxide dismutase, catalase (CAT), GSH peroxidase, and GSH reductase, were estimated. CdCl₂ injection induced a significant elevation in cadmium concentration, lipid peroxidation, and nitric oxide and caused a significant depletion in GSH content compared to controls, along with a remarkable decrease in antioxidant enzymes. Oxidative stress induction and cadmium accumulation in the liver were successfully ameliorated by F. ananassa (strawberry) pre-administration. In addition, the pre-administration of strawberry decreased the elevated gene expression of the pro-apoptotic Bax gene as well as the protein expression of caspases-3 in the liver of CdCl₂-injected rats. In addition, the reduced gene expression of anti-apoptotic Bcl-2 was increased. Our results show an increase in the expression of tumor necrosis factor α in the liver of rats treated with cadmium. In sum, our results suggested that F. ananassa successfully prevented deleterious effects on liver function by reinforcing the antioxidant defense system, inhibiting oxidative stress and reducing apoptosis.     

The Effect of N-acetylhomocysteine and its Thiolactone on the Distribution and Excretion of Mercury in Methyl Mercuric Chloride Injected Mice

Abstract: The distribution and excretion of mercury was studied in mice given a single intravenous dose of 5 μmol/kg of methyl mercuric chloride. Intravenous treatment with N-acetylhomocysteine (10 mmol/kg) increased the urinary excretion of mercury. The corresponding thiolactone mixed into the feed of the mice turned out to be more effective in removing mercury from the body. The toxicity of the thiolactone seemed to be remarkably low compared to other sulphur containing agents. Mercury deposited in the brain was mobilized by oral administration of the thiolactone even if the treatment was delayed until 5 days after the injection of methyl mercury. The results indicate that the formation of a N-acetylhomocysteine-methyl-mercuric-complex is responsible for this effect.     

镉对在体大白鼠心肌动作电位的影响

在体大白鼠,采用浮置微电极观察氯化镉对心脏动作电位的影响。结果表明,1％CaCl_2O.2ml静脉注射使动作电位时程缩短,振幅降低,周期延长。提示镉可能有降低心肌细胞自律性,抑制兴奋性及传导性等作用。     

Methyl Mercuric Compounds in Rat Bile

Abstract: Methyl mercuric glutathione is the predominant methyl mercuric compound in rat bile following exposure to methyl mercuric chloride. Methyl mercuric chloride also forms methyl mercuric glutathione when added to rat bile in vitro. A small amount of methyl mercuric cysteine is always found in the bile of exposed animals. This amount increases on storage of the bile, and may include most of the metal present. Exchange of the methyl mercuric ion takes place between cysteine and glutathione. Methyl mercuric glutathione releases methyl mercuric cysteine on storage, probably by autolysis, but an action of enzymes cannot be ruled out. Final conclusions cannot be drawn as to which methyl mercuric compound is actually transported from the liver cell to the bile.