砷对睾丸补体抑制水平的影响及硒的拮抗作用

目的　研究砷对睾丸补体抑制水平的影响及硒的拮抗效应 ,以探讨砷的生殖毒性的免疫机制。方法　补体溶血抑制实验 ,测定大鼠睾丸及血清补体抑制水平。结果　以 4.6 mg/ kg体重三氧化二砷 (As2 O3)灌胃大鼠 5周 ,大鼠睾丸及血清补体抑制率显著低于对照组 (P <0 .0 5 )。染砷大鼠同时分别给予含硒 10 0 ,2 0 0μg/ kg体重的康强硒 ,睾丸及血清补体抑制率比染砷组显著升高 (P <0 .0 5 ) ,与对照组差异不显著 (P >0 .0 5 )。结论　砷可导致大鼠睾丸补体抑制水平下降 ,可能与砷引起的精子畸变、流产、不育有关 ,硒可有效拮抗砷的生殖毒性     

不同剂量硒对大鼠四种组织器官硒蓄积浓度的影响

目的观察不同剂量硒喂饲SD大鼠后,对其肝、肾、血、睾丸中硒蓄积浓度的影响。方法将40只4周龄雄性断乳大鼠,以缺硒饲料（BD）喂饲35 d后,按体重随机分为4组,每组10只。1组继续BD饲养,其它3组的饲料在BD基础上分别加含0.25、3.0、5.0 ppm亚硒酸钠形式的硒。经过28 d硒蓄积性毒性试验,处死采样,测定肝、肾、血细胞（全血离心沉淀）和睾丸中硒元素蓄积浓度。结果适量硒摄入的大鼠肾与睾丸的硒浓度最高。高硒暴露时,组织硒浓度依次为：肾〉肝〉血细胞〉睾丸。高浓度硒对4种组织硒浓度变化的影响依次是：血细胞〉肝〉肾〉睾丸。结论肝与血细胞硒蓄积浓度的变动幅度大,提示它们对维持其它组织硒含量的相对稳定具有重要作用;而睾丸硒蓄积量的稳定性印证了该元素对雄性生殖功能的重要性.     

硒对氟致大鼠雄性生殖损害的拮抗研究

研究了饮水中亚硒酸钠的浓度分别为０．５、２．０、４．０ｍｇ／Ｌ时对氟致大鼠雄性生殖系统损害的影响。结果表明，适量亚硒酸钠对饮用１５０ｍｇ／Ｌ氟化钠所致雄性大鼠附睾精子总数减少，活动率降低，血清和睾丸组织中ＬＰＯ含量升高，睾丸乳酸脱氢酶（ＬＤＨ）及其同工酶（ＬＤＨｘ）活性降低，附睾ＡＴＰ酶活性抑制等损害作用具有明显的拮抗作用，以２．０ｍｇ／Ｌ亚硒酸钠的拮抗作用最佳。较低浓度的（０．５ｍｇ／Ｌ）亚硒酸     

低硒对雄性大鼠性腺发育和分泌功能的影响

目的　研究雄性动物性腺的发育和功能与硒的关系。方法　分别以低硒饲料、补硒饲料和常规饲料喂养刚分窝的雄性Ｗ ｉｓｔａｒ 大鼠１４ 周和３９ 周后,分别采用２,３－二氨基萘（ＤＡＮ）荧光分光光度法和化学发光酶免疫法测定血和睾丸硒含量及血浆睾酮水平等指标。结果　饲养１４ 周后,低硒组大鼠不仅血和睾丸硒含量以及睾丸谷胱甘肽过氧化物酶（ＧＰｘ）活性显著低于对照组,而且其精囊腺重量、精囊腺指数和血浆睾酮水平等也显著低于对照组,但其睾丸中脂质过氧化物（ＬＰＯ）水平则显著高于对照组（ Ｐ ＜ ０．０５）。在低硒饲料中补充一定量的硒可在一定程度上纠正这些变化。饲养３９ 周后,低硒组精囊腺指数进一步降低,与对照组的差异达极显著程度（ Ｐ ＜ ０．０１）,甚至睾丸指数也降至显著低于对照组。结论　这些结果提示,硒不足对雄性动物性腺的发育和分泌功能有不良影响,适当补硒可作为男性不育症的辅助治疗手段。     

外源性雄激素通过诱导自噬促大鼠睾丸萎缩

目的探讨外源性雄激素对大鼠睾丸萎缩的影响及其可能机制。方法 48只SD雄性大鼠随机分成6组,每组8只:对照组(control)、雄激素(丙酸睾丸酮,TP)组、雄激素+氯喹(TP+CQ)组、雄激素+甘草甜素(TP+Gly)组、氯喹(CQ,自噬抑制剂)组、甘草甜素〔Gly,高迁移率族蛋白(HMGB) 1抑制剂〕组。各组分别处理21 d后,测量体重、睾丸湿重、睾丸指数;采用HE染色法观察睾丸组织病理学改变; Western印迹法大鼠睾丸组织Beclin-1、LC3B-Ⅱ、p62、HMGB1蛋白表达情况。结果给予大鼠TP干预21 d后,大鼠睾丸湿重、睾丸指数均显著降低(P<0. 01);睾丸生精小管发生萎缩,各级生精细胞排列紊乱、层数减少,未见成熟的精子;睾丸组织Beclin-1、LC3B-Ⅱ和HMGB1蛋白表达均显著上调(P<0. 05),p62蛋白表达无明显变化(P>0. 05)。联合给予TP和CQ后,大鼠睾丸指数显著增加(P<0. 05);生精小管和各级生精细胞损伤明显改善,可见到成熟的精子;睾丸组织Beclin-1、LC3B-Ⅱ和HMGB1蛋白表达水平均显著下调(P<0. 05),p62蛋白表达仍无明显变化(P>0. 05)。联合给予TP和Gly后,各观测指标变化与联合给予TP和CQ后结果类似,且两组各指标均无明显差异(P>0. 05)。结论外源性雄激素可能通过上调自噬水平引发大鼠睾丸萎缩病理过程发生,此过程中HMGB1可能调节自噬水平改变。     

黄绿青霉素对低硒低蛋白大鼠心肌组织形态结构的影响

目的 观察黄绿青霉素(CIT)对低硒低蛋白大鼠心肌组织形态结构的影响.方法 将48只Wistar 雄性大鼠按2×2析因设计分为4组:低硒低蛋白加毒素组、低硒低蛋白无毒素组、常硒常蛋白加毒素组和常硒常蛋白无毒素组,每组12只.首先用常硒常蛋白或低硒低蛋白饲料喂养大鼠2个月,然后加毒素各组饲料中另加入8 mg·kg-1·d-1 CIT喂养2个月,再以加入10 mg·kg-1·d-1 CIT的饲料喂养2周,而无毒素各组继续喂饲原饲料.在实验终期将大鼠麻醉后进行股动脉放血处死,称量心脏质量,计算心脏质量指数,光镜下观察心肌组织病理学变化.结果 低硒低蛋白加毒素组、低硒低蛋白无毒素组、常硒常蛋白加毒素组和常硒常蛋白无毒素组心脏质量指数分别为( 3.65±0.45)×10-3、(3.05±0.19)×10-3、(3.83±1.06)×10-3、(3.31±0.52)× 10-3.析因分析结果显示,CIT因素对大鼠心脏质量指数有明显影响作用(F=8.524,P＜0.05),而“硒+蛋白”因素未见明显影响作用(F=1.347,P＞0.05),且二者间不存在交互作用(F=0.048,P＞0.05).光镜下低硒低蛋白加毒素组大鼠心肌细胞血管周围出现纤维组织增生,细胞中出现明显的收缩带；低硒低蛋白无毒素组大鼠出现少量心肌细胞固缩；常硒常蛋白加毒素组大鼠心肌细胞出现坏死灶,并伴有炎性细胞浸润,出现较多固缩细胞；常硒常蛋白无毒素组大鼠心肌细胞群排列整齐,层次清晰,结构完好.结论 CIT可引起大鼠心肌组织变性坏死,低硒低蛋白也可造成大鼠心肌组织轻微损伤,而两因素叠加在一起时心肌损伤较严重.     

硒代甲硫氨酸对胃癌细胞蛋白表达谱的影响

目的:分析硒代甲硫氨酸对胃癌AGS细胞蛋白表达谱的影响.方法:应用Hoechst荧光染色法及流式细胞术观察硒代甲硫氨酸对胃癌AGS细胞凋亡的影响;应用双向凝胶电泳技术分析硒代甲硫氨酸对胃癌AGS细胞蛋白表达的影响.结果:胃癌AGS细胞在含硒代甲硫氨酸培养液中培养5 d后,部分细胞的细胞核内出现凋亡小体,含硒代甲硫氨酸培养液中AGS细胞的凋亡率显著高于正常培养液组(53.98%±9.88% vs 15.76%±9.03%,P＜0.01).双向电泳技术筛选出12个表达差异的蛋白.结论:硒代甲硫氨酸可以影响胃癌AGS细胞蛋白的表达.这些差异表达的蛋白可能与胃癌细胞凋亡有关.     

燃煤型氟中毒大鼠睾丸组织中SCFmRNA的表达变化及意义

目的观察睾丸干细胞因予（SCF）在燃煤型氟中毒大鼠睾丸组织中的表达变化。方法将20只雄性SD大鼠随机分为对照组、低氟组、中氟组、高氟组（后三组为染毒组）,各5只。除对照组外,余各组均喂饲含不同比例的燃煤型氟中毒病区煤烘玉米的饲料,制作燃煤型氟中毒动物模型。90d后,取大鼠睾九,采用透射电镜观察睾丸支持细胞的超微结构,用RT-PCR法检测睾丸组织中SCFmRNA。结果氟中毒模型成功建立。电镜观察可见染毒组睾丸组织中支持细胞核高度畸形染色质边集,胞质空泡化,初级溶酶体增多。低、中、高氟组睾丸组织SCFmRNA相对表达量分别为0．71±0．05、0．68±0．01、0．49±0．02,均低于对照组的0．73±0．03（P分别〈0．05、0．01、0．01）;低、中、高氟组睾丸组织中SCFmRNA表达依次降低（P均〈0．05）。结论燃煤型氟中毒能降低大鼠睾丸组织中SCFmRNA表达;其SCFmRNA下调和睾丸支持细胞损伤在氟中毒所致生精障碍中可能起重要作用。     

低硒大鼠心肌硫氧还蛋白还原酶的活性和表达研究

目的 探讨低硒状态下大鼠心肌硫氧还蛋白还原酶（TR）的活性和表达变化，分析体内硒元素含量改变对硫氧还蛋白还原酶活性的影响及其可能的机制。方法 用低硒饲料喂养断乳2周的Wistar大鼠14周，分别采用生物化学方法、Western blot和Northern blot杂交检测心肌组织中TR的活性改变及TR蛋白、基因表达变化。结果 低硒组大鼠心肌TR活性降低至对照组的63.8%，差异有非常显著意义。蛋白杂交的峰面积密度扫描结果显示，常硒组为3438，低硒组为2067。Northern blot结果显示低硒组与对照组无明显差异。结论 低硒能够降低心肌TR的活性和蛋白表达水平，但并不影响此酶的基因表达，提示低硒导致心肌TR活性降低可能是由于TR蛋白合成过程中SeCys插入减少所致。     

低硒大鼠microRNA表达谱的变化

目的 探讨低硒大鼠microRNA表达谱的变化。方法 将30只SD大鼠随机分为对照组、低硒组及补硒组,每组各10只,对照组喂养标准饲料,低硒组喂养低硒饲料,补硒组喂养低硒饲料14周后再给予亚硒酸钠补硒3周。各组喂养17周后,检测大鼠的血硒水平。提取各组大鼠心肌组织RNA进行microRNA基因芯片检测,寻找低硒大鼠与正常大鼠microRNA的表达差异。采用GO分析等生物学方法对差异性表达的microRNA基因进行深度的分析,并通过RT-qPCR进行验证。结果 成功构建了SD大鼠低硒模型（血硒含量0 .026 ng/L）,低硒组大鼠血硒水平与对照组相比明显降低(P<0.05),补硒后又明显增加（P<0.05）。通过microRNA基因芯片检测低硒组筛选出显著差异性表达基因共30个,上调基因中表达最显著的为:miR-374,miR-16,miR-199a-5p,miR-195和miR-30e*,下调基因中表达最显著的为:miR-3571,miR-675和miR-450a*。 其中miR-374表达量最高,与低硒密切相关。结论 低硒大鼠中miR-374,miR-16,miR-199a-5p,miR-195,miR-30e*,miR-3571,miR-675,miR-450a*表达显著异常,其中miR-374与低硒关系最为密切。为MicroRNA在克山病的诊断及治疗方面研究提供实验依据。     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Serological survey of HIV and syphilis in pregnant women in Madagascar

Objectives Peripartal transmission of human immunodeficiency virus (HIV) and Treponema pallidum, the causative agent of syphilis, leads to severe consequences for newborns. Preventive measures require awareness of the maternal infection. Although HIV and syphilis testing in Madagascar could be theoretically carried out within the framework of the national pregnancy follow‐up scheme, the required test kits are rarely available at peripheral health centres. In this study, we screened blood samples of pregnant Madagascan women for HIV and syphilis seroprevalence to estimate the demand for systemic screening in pregnancy. Methods Retrospective anonymous serological analysis for HIV and syphilis was performed in plasma samples from 1232 pregnant women that were taken between May and July 2010 in Ambositra, Ifanadiana, Manakara, Mananjary, Moramanga and Tsiroanomandidy (Madagascar) during pregnancy follow‐up. Screening was based on Treponema pallidum haemagglutination tests for syphilis and rapid tests for HIV, with confirmation of positive screening results on line assays. Results Out of 1232 pregnant women, none were seropositive for HIV and 37 (3%) were seropositive for Treponema pallidum. Conclusions Our findings are in line with previous studies that describe considerable syphilis prevalence in the rural Madagascan population. The results suggest a need for screening to prevent peripartal Treponema pallidum transmission, while HIV is still rare. If they are known, Treponema pallidum infections can be easily, safely and inexpensively treated even in pregnancy to reduce the risk of transmission.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.