毛兰素对人肝癌Huh7细胞的抑制作用

研究了从鼓槌石斛中分离得到的低分子量天然化合物毛兰素在体外对人肝癌Huh7细胞的增殖抑制作用,并探讨其诱导细胞凋亡的分子机制.实验结果显示:毛兰素能显著抑制肝癌Huh7细胞的增殖,且随着药物浓度与时间增加其抑制率呈明显的剂量时间效应,其48 h半数抑制浓度IC50为37.4 nmol/L;毛兰素能诱导人肝癌Huh7细胞凋亡并使其细胞周期阻滞于G2-M期;分子机制研究显示毛兰素可抑制Akt激酶活性、下调Mcl-1蛋白表达以及激活PARP活性从而导致其对Huh7癌细胞的增殖抑制作用.以上结果初步表明毛兰素对肝癌防治具有潜在药用价值.图5参17     

孕期低剂量镉暴露对不同性别胎鼠肝脏发育的影响及其分子调控机制的研究

为探究镉对胎儿肝脏发育的毒性作用.拟选用15只性成熟的8周龄的雌性C57BL/6小鼠,与雄鼠交配见栓后,于妊娠第7.5 d(Embryonic 7.5,E7.5)时,随机分为3组(每组5只),分别通过饮用水暴露法饲喂0、20和40 mg·L^-1的氯化镉溶液,并于E14.5 d时收集各组小鼠的胎儿肝脏等组织.通过Ki67和TUNEL染色方法探究镉对不同性别胎鼠肝脏的增殖功能和凋亡功能的影响,并通过PCR芯片筛查和实时定量PCR方法检测镉处理组的雌性和雄性胎鼠肝脏中与细胞增殖和凋亡功能相关基因的表达变化.此外,我们还将通过石墨炉火焰原子吸收技术对镉处理组的雌性和雄性胎鼠的镉含量进行检测.结果显示:孕期低剂量镉暴露对胎儿体重、胎肝重量和肝脏指数均无显著性影响.在本实验条件下,镉对胎鼠肝脏的凋亡功能无显著性影响,但对增殖功能具有抑制作用,且该抑制作用具有雌性依赖性的特征.镉特异性诱导雌性胎鼠肝脏中NF1等多个细胞增殖功能相关基因以及TGF-β1信号通路分子的表达失衡;但对雄性胎鼠肝脏中相关基因的表达水平无显著性影响.镉在雌性胎儿组织中的积累量显著高于雄性胎儿组织.综上所述,孕期低剂量镉暴露特异性抑制雌性胎儿肝脏的细胞增殖功能,并诱导雌性胎儿肝脏中NF1等多个增殖功能相关基因以及TGF-β1信号通路分子的表达失衡,该性别依赖性的抑制作用可能与镉在雌性胎儿中相对较高的积累量相关.     

丙溴磷影响海洋微藻生长机理的初步研究

研究了丙溴磷对三角褐指藻和青岛大扁藻生长的影响及其可能的机理。结果显示，低浓度的丙溴磷可以刺激它们的生长，高浓度的丙溴磷则对其生长产生抑制作用；低浓度丙溴磷还使藻细胞的脂质过氧化程度在低水平增高，ＳＯＤ活性有所降低；高浓度时则使其指质过氧化程度过量升高，ＳＯＤ活性显著下降，加入抗氧化剂不仅可抑制低浓度丙溴磷对微藻生长的刺激效应，而且能缓解高浓度丙溴磷对微藻的毒害作用，因此，丙溴磷作用于微灌的抗氧化     

Endocrine modulation, inhibition of ovarian development and hepatic alterations in rainbow trout exposed to polluted river water

Under laboratory conditions, female rainbow trout were exposed to graded concentrations of water from the River Lambro, a polluted tributary of the River Po, and to the effluent of a large wastewater treatment plant which flows into the River Lambro. In field exposures, trout were held in cages in the River Po upstream and downstream from the confluence of the River Lambro. After 10-day (laboratory) and 30-day (laboratory and field) exposures, trout were examined for several chemical, biochemical and histological endpoints. The results indicated that exposure to complex mixtures of chemicals, including estrogen receptor agonists, aryl-hydrocarbon receptor agonists, and probably antiandrogens, had occurred. Exposure altered the plasma levels of 17β-estradiol and testosterone, and some treatments also enhanced the activity of hepatic ethoxyresorufin O-deethylase. Gonadal histology showed varying levels of degenerative processes characterised by oocyte atresia, haemorrhages, melano-macrophage centres (MMCs), and oogonia proliferation. Liver histology showed less severe effects.     

Cytogenetic status of human lymphocytes after exposure to low concentrations of p,p'-DDT, and its metabolites (p,p'-DDE, and p,p'-DDD) in vitro

Despite that the use of DDT has been restricted for more than 40 years to malaria affected areas, low doses of this pesticide and its metabolites DDE and DDD can be found in the environment around the world. Although it has been shown that these pollutants induce cell and DNA damage, the mechanisms of their cytogenotoxic activity remains largely unknown. This study looks into their possible genotoxic effects, at doses that can be found in body fluids, on human lymphocytes using the cytokinesis-block micronucleus assay and the comet assay. After exposure for 1, 6, and 24 h compounds p,p′-DDT (0.1 μg mL⁻¹), p,p′-DDE (4.1 μg mL⁻¹), and p,p′-DDD (3.9 μg mL⁻¹) showed increase in DNA damage. The most significant results were observed at exposure period of 24 h where number of micronucleated cells increased from control 2.5 ± 0.71 to 23.5 ± 3.54, 13.5 ± 0.71, and 16.5 ± 6.36 for DDT, DDE, and DDD, respectively. Similar effect was observed using comet test where the percentage of DNA in comets tail increased from control 1.81 ± 0.16 to 17.24 ± 0.55, 11.21 ± 0.56 and 9.28 ± 0.50 for each compound, respectively. At the same time Fpg-comet assay failed to report induction of oxidative DNA damage of these pollutants. Additionally, the type of cell death was determined using diffusion assay and necrosis dominated. Our findings suggest that even at low concentrations, these pesticides could induce cytogenetic damage to human peripheral blood lymphocytes and in that manner have the impact on human health as well.     

水文气象因素对东南山区水库硅藻异常增殖的影响

硅藻异常增殖是影响我国许多水库水质安全的生态灾害.为揭示水库硅藻异常增殖的影响因素,以我国东南丘陵地区大(Ⅱ)型水库天目湖沙河水库为例,基于8年逐月浮游植物群落结构及相关环境因子的监测,分析了硅藻(Bacillariophyta)及其优势属生物量与温度、降雨、水位、营养盐等环境因子之间的关系.结果表明,春季硅藻及其优势属的生物量主要受温度的影响,与水文、营养盐关系较弱;不同硅藻优势属与水温的关系差异较大:针杆藻(Synedra)的最佳生长温度为27℃,小环藻(Cyclotella)与曲壳藻(Achnanthes)的最佳生长温度为19℃,直链藻(Melosira)适合在低温下生长,生物量随温度升高而降低;硅藻生物量与环境因子的多元统计分析表明,硅藻总生物量、针杆藻和曲壳藻等优势属生物量峰值与降雨量显著性正相关(P0.05),小环藻生物量峰值与总磷、降雨量和水位显著性正相关,而与换水率显著性负相关,直链藻生物量峰值与总磷显著性正相关.年度硅藻峰值强度可以用降雨量强度和时间、冬春季的积温和溶解性总磷浓度等综合因素拟合预测.研究表明,对于我国东南丘陵山区中营养水平的水库而言,硅藻优势属的异常增殖事件受水文气象因素异常事件的影响较大,相比较而言对氮磷营养盐响应偏弱;在防控水库硅藻异常增殖灾害方面,除了积极开展流域营养盐削减措施之外,应当密切关注极端天气综合影响,采取相应的水文调节措施,开发切实有效的灾害预警技术.     

环境内分泌干扰物促进乳腺细胞增殖的分子机制研究进展

乳腺癌是女性中常见的癌症,EDCs（environmental endocrine disrupting chemicals,环境内分泌干扰物）具有雌激素活性,能促进乳腺细胞的增殖,明确EDCs在乳腺癌细胞增殖中的作用和机制,有助于乳腺癌的预防.在归纳整理国内外相关研究基础上,总结了EDCs通过激活雌激素受体信号通路、抑制细胞凋亡和改变细胞周期等方面促进乳腺细胞的增殖,并对其分子机制进行了全面综述.EDCs促进乳腺细胞增殖的分子机制有:①EDCs通过与雌激素核受体（nERs）结合形成二聚体,改变受体构象,并结合到靶基因雌激素响应元件（ERE）上,进而调控增殖相关靶基因转录和蛋白表达;②EDCs也可通过与雌激素膜受体（mERs）结合,激活快速非基因组信号通路,改变靶蛋白活性或靶基因表达;③EDCs也可通过上调凋亡抑制蛋白Bcl-2和Bcl-xL的表达,抑制细胞凋亡;④EDCs还可通过上调细胞周期蛋白（cyclin）表达、提高周期依赖性蛋白激酶（CDKs）活性,加快细胞周期;⑤EDCs通过基因组、非基因组信号途径的交互,上调cyclin D和c-Myc表达,再通过CDK磷酸化细胞周期调节因子Rb蛋白,释放转录因子E2Fs,加速细胞从G₁期向S期的转变,促进细胞增殖.建议今后从与内源激素交互、影响雌激素E₂合成以及低剂量联合作用3个方面来探讨EDCs对乳腺细胞的增殖机制,以期为乳腺致癌物的筛查、乳腺癌预防和治疗以及乳腺细胞增殖机制的深入研究提供参考.      

海洋赤潮藻球形棕囊藻在氮磷富营养下的细胞增殖

利用常见海洋赤潮微藻球形棕囊藻(Phaeocystis globosa)为试验研究材料,以舵海洋微藻营养液为对照(1P1N:磷质量浓度为5×10-3g·L-1.氮质量浓度为75×10-3g·L-1),设置3组富磷和富氮营养处理(3P1N:磷质量浓度为15×10-3 g·L-1,氮质量浓度为75×10-3 g·L-1;1P3N:磷质量浓度为5××10-3 g·L-1,氮质量浓度为225×10-3 g·L-1;3P3N:磷质量浓度为15××10-3 g·L-1,氮质量浓度为225×10-3 g·L-1),利用细胞记数和叶绿素荧光测定等方法研究了藻细胞在不同富磷和富氮条件的增殖情况.结果显示,不同浓度磷和氮营养下的藻体荧光值变化在试验周期内均呈现"S"型曲线,表明藻细胞的生长经历缓慢期,快速期和平缓期3个阶段;同时,不同的富磷和富氮营养条件对球形棕囊藻的叶绿素荧光值有一定的影响,其中在对照1P1N下的藻体荧光值最低,在试验结束时(第10天)只有850 μg·L-1,而在3P1N,1P3N和3P3N条件下的藻体荧光值均达到900 μg·L-1以上,显著高于1P1N下的藻体荧光值,表明富磷和富氮营养可以促进藻细胞的生长增殖,但在试验设置的不同富磷和富氮营养下的藻体荧光值之间没有显著的差异.就不同磷和氮营养条件下的藻最大比生长速率而言,3P3N和3P1N条件下的最大,均达到0.77 d-1,明显高于1P1N和1P3N条件下的藻最大比生长速率(分别只有0.70 d-1和0.69 d-1).此外,试验结束时细胞密度的变化趋势与藻体荧光值相似,富磷和富氮营养条件下的细胞密度显著高于1P1N下的细胞密度,而富磷和富氮营养条件下的细胞密度间也不存在显著的差异.研究结果揭示,水体中的高磷和高氮营养浓度是导致藻细胞大量快速增殖的一个主要因素,而利用叶绿素荧光来测定藻细胞增殖是一种快速、简便,灵敏和可靠的方法,可在今后赤潮监测过程中多加利用,以能及时、准确地预测预报赤潮爆发.从而减少其对环境和经济的影响.     

Assessment of biological effects of environmental pollution along the NW Mediterranean Sea using red mullets as sentinel organisms

A biomonitoring program was carried out in spring and autumn in three pollution hot-spots and sensitive areas of the NW Mediterranean Sea using red mullets (Mullus barbatus) as sentinel organisms and a battery of biomarkers together with gonad histology. In fish from anthropogenic impacted areas (Fos-sur-mer, Cortiou, Arenzano, Delta of Ebro) lysosomal membrane destabilization occurred indicating disturbed health. There were no significant differences in metallothionein (MT) levels among stations. Peroxisomal acyl-CoA oxidase (AOX) activity was highest in fish from Cortiou. Both MT levels and AOX activities were significantly correlated with gamete development. Prevalence of melanomacrophage centers were high in Cortiou in all samplings and in Fos-sur-mer in September samplings. In conclusion, the application of a battery of biomarkers in red mullets provided relevant data for the assessment of environmental pollution in the NW Mediterranean Sea but also showed the difficulties of using native fish as sentinels. For future studies caging strategies are recommended.     

三峡水库水生态环境保护与增殖渔业发展对策研究

三峡水库试验性蓄水175m成功后,水库水生态环境的管护成为水库管理的重点工作之一。针对目前三峡水库渔业的现状、取得的进展、存在的问题展开调研。在实地考察调研的基础上,提出了巩固取消三峡水库网箱养鱼的成果,防止反弹;开展三峡水库增殖渔业研究;建立三峡水库渔业开发总公司,实行公司化运作,实现渔业科学、有序、可持续的良性发展;加强水库增殖渔业的行政管理等建议。为政府在完善保护三峡水库水质和发展增殖渔业决策时提供参考。