应激大鼠胃黏膜氧化应激指标受褪黑素影响的研究

目的探讨褪黑素干预应激大鼠胃黏膜氧化应激指标影响的研究.方法采用浸水-束缚(WIR)应激实验复制大鼠应激性溃疡模型.应激前30 min,MT(melatonin)5、20mg·kg-1和应激组大鼠分别腹腔注射MT 5、20mg·kg-1和等体积生理盐水.应激6h后,观察各组大鼠胃黏膜病变情况,对溃疡指数(UI)进行评分,同时检测各组大鼠胃黏膜内丙二醛(MDA)含量、胃黏膜超氧化物歧化酶(SOD)活性和还原型谷胱甘肽(GSH)水平.结果WIR应激6h后,应激组大鼠胃黏膜MDA水平显著高于对照组(P＜0.01).MT 5、20mg·kg-1组较应激组MDA水平显著下降(P＜0.01),且MT 20mg·kg-1组显著低于MT 5mg·kg-1组(P＜0.01).应激组大鼠SOD、GSH活性较对照组明显降低(P＜0.01),MT 5、20mg·kg-1组较应激组SOD、GSH活性有升高趋势.比较各组UI发现,MT 5、20mg·kg-1组UI显著低于应激组(P＜0.01),其中MT 20mg·kg-1组UI显著低于MT 5mg·kg-1组(P＜0.05).结论褪黑素通过其抗氧化的作用对应激大鼠胃黏膜损伤起保护作用.     

褪黑素对过氧化氮损伤心肌细胞一氧化氮的影响

目的探讨氧化损伤时心肌细胞一氧化氮(NO)生成的变化和褪黑素(MT)的保护作用.方法分离培养原代心肌细胞,用NO试剂盒检测细胞培养液中NO含量,硫代巴比妥酸法测定细胞中丙二醛(MDA)含量,荧光探针DCFH-DA标记细胞,用激光共聚焦显微镜观察心肌细胞内总的自由基水平.结果与对照组相比,100 μmo1/L的H2O2作用60min可使培养液中NO浓度、心肌细胞中MDA含量和心肌细胞内总的自由基水平明显增加(分别为22.4±2.6 vs 97.3±2.4 nmol/L、1 23±0.05 vs 3.65±0.20 nmol/106cells和86±6.9 vs 742±13.4,P＜0.01);加入MT干预后,H2O2引起的NO、MDA和细胞内总的自由基水平的升高被明显抑制,两组相比显著差异(P＜0.01).结论H2O2造成心肌细胞氧化损伤时,心肌细胞合成的NO增多并参与了损伤机制,MT不仅能使心肌细胞内总的自由基水平下降,也能抑制NO的过度增加,从而起到保护心肌细胞的作用.     

褪黑素对日本血吸虫致小鼠肝纤维化作用的影响

目的观察褪黑素(melatonin,MT)对日本血吸虫致小鼠肝纤维化的影响。方法建立日本血吸虫致小鼠分肝纤维化模型、分别测定血清及肝匀浆中的谷氨酸氨基转移酶(ALT)、天门冬氨酸氨基转基酶(AST)、丙二醛(MDA)和谷胱甘肽过氧化物(GSH-px)含量,测定肝组织羟脯氨酸(HYP)含量,观察肝组织病理学的变化。结果 MT给药组(0.5、1.0mg·kg~(-1))能使模型小鼠降低的超氧化物歧化酶(SOD)、GSHpx活性明显升高;并能显著降低模型小鼠升高的MDA水平;肝组织HYP含量明显升高与感染对照组相比有差异显著(P<0.05);同时,MT能明显减轻肝脏炎细胞浸润及坏死程度;抑制胶原纤维的增生。结论 MT可能通过清除自由基等作用对日本血吸虫致小鼠肝纤维化有减轻作用。     

病毒性心肌炎小鼠心肌线粒体结构和功能变化

目的:探讨病毒性心肌炎(VMC)小鼠心肌线粒体结构和功能变化。方法:雄性Balb/c小鼠随机分为柯萨奇B3病毒(CVB3)感染组和对照组。分别采用电镜和形态计量学方法观察心肌线粒体形态、数量和膜磷脂定位,酶细胞化学法分析线粒体细胞色素氧化酶(CCO)和琥珀酸脱氢酶(SDH)活性,反相高效液相色谱法测定心肌组织腺苷酸(ATP、ADP和AMP)含量。结果:CVB2感染组小鼠心肌线粒体大量破坏,膜磷脂严重缺失、定位改变,CCO和SDH活性降低,腺苷酸(ATP、ADP和AMP)含量下降。结论:VMC心肌线粒体结构严重破坏、功能明显下降,心肌细胞存在产能障碍。     

褪黑素对D-半乳糖拟衰老小鼠海马线粒体膜流动性的影响

目的　研究褪黑素 (MT)对拟衰老小鼠海马线粒体膜流动性的影响。方法　 D-半乳糖诱导昆明小鼠衰老同时腹腔注射外源性褪黑素连续 8w,以 DPH为荧光探针 ,检测小鼠海马线粒体膜粘滞系数 ,同时测定线粒体悬液丙二醛含量。结果　衰老组小鼠海马线粒体膜流动性降低 ,MDA生成增加 ,给予 MT (5mg/ kg· d- 1　 ip)明显提高膜流动性 ,MDA生成显著减少 (均 P<0 .0 1 )。结论　药理剂量 MT (5mg/ kg)对 D-半乳糖衰老小鼠膜脂质过氧化损伤具保护作用     

茜草多糖对衰老模型小鼠心肌线粒体酶活性影响的实验研究

目的探讨茜草多糖对衰老小鼠心肌线粒体酶活性的影响。方法通过建立D半乳糖人工致衰小鼠模型,测定心肌线粒体超氧化物歧化酶(SOD),Na+K+ATP酶和Ca2+ATP酶的活性。结果衰老模型组SOD、Na+K+ATP酶和Ca2+ATP酶的活性均明显降低;茜草多糖可升高衰老模型组SOD、Na+K+ATP酶和Ca2+ATP酶活性(P<0.05,P<0.01)。结论茜草多糖对衰老模型小鼠心肌线粒体有保护作用。     

大枣对D-半乳糖致衰老小鼠钙稳态影响的实验研究

目的　探讨大枣对维持细胞内钙稳态的作用及机制。方法　本实验以D 半乳糖致衰老小鼠为研究对象 ,分别以大、中、小剂量的大枣水煎剂灌胃 45d,测定了青年、老年小鼠红细胞超氧化物歧化酶 (SOD)活性 ,心肌线粒体内丙二醛 (MDA)含量 ,心肌细胞膜Na K ATPase、Ca2 ATPase活性 ,心肌组织及线粒体Ca2 含量变化 ,同时 ,观察不同剂量大枣对老年小鼠上述指标的影响。结果　红细胞SOD活性、心肌细胞膜Na K ATPase、Ca2 ATPase活性、心肌线粒体Ca2 含量变化随增龄而下降 ;心肌线粒体内MDA含量、心肌组织Ca2 含量随增龄而上升。大枣可提高小鼠红细胞SOD活性 ,心肌细胞膜Na K ATPase、Ca2 ATPase活性、心肌线粒体Ca2 含量 ,并能降低心肌线粒体内MDA含量、心肌组织Ca2 含量。在各给药组中以大枣大剂量组的作用最强。结论　 (1 )大枣能增强机体抗氧化能力 ,减少自由基对生物膜的损伤 ,维持细胞内钙稳态 ,具有一定的抗衰老作用 ;(2 )自由基与钙超载协同作用可能是导致衰老的重要原因。     

浅低温对老年大鼠心肌缺血再灌注损伤的保护作用

目的探讨浅低温对老年大鼠心肌缺血再灌注损伤的保护作用。方法将48只老年大鼠随机分为浅低温组和对照组,每组24只。对照组大鼠在37℃平衡灌流30 min,缺血30 min,再灌注120 min;浅低温组大鼠在37℃平衡灌流30 min,缺血30 min,34℃浅低温下再灌注120 min。检测心室线粒体和胞质细胞色素C水平,心肌组织中丙二醛(MDA)、三磷酸腺苷(ATP)含量和超氧化物歧化酶(SOD)活力及心肌梗死范围。结果浅低温组线粒体细胞色素C水平高于对照组(P<0.05),胞质细胞色素C低于对照组(P<0.05)。浅低温组大鼠试验后心肌梗死面积低于对照组(P<0.05)。浅低温组大鼠心肌组织中MDA含量低于对照组(P<0.05),ATP含量和SOD活力高于对照组(P<0.05)。结论浅低温对老年大鼠心肌缺血再灌注损伤具有保护作用,其机制可能与浅低温能够减少心室线粒体中细胞色素C的扩散、降低心肌组织MDA含量、升高心肌组织中ATP含量和SOD活力有关。     

褪黑素对糖尿病大鼠心肌MDA、CAT及GSH-Px含量和AGE、RAGE表达的影响

目的研究褪黑素(RAGE)对糖尿病大鼠心肌组织中丙二醛(MDA)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-Px)含量的影响及糖基化终末产物(AGE)和糖基化终末产物受体(RAGE)表达水平的改变。方法清洁级雄性Wistar大鼠,高脂高糖饮食,配合腹腔注射链脲佐菌素诱导糖尿病模型,随后给予低剂量[10 mg/(kg体重·d)]和高剂量[20 mg/(kg体重·d)]MT灌胃16 w。比色法测定心肌组织中MDA、CAT和GSH-Px含量变化;HE染色观察心肌组织病理改变;超敏二步免疫组化染色测定心肌组织中AGE和RAGE蛋白表达。结果经过MT处理16 w后,与模型组比较,低剂量MT组和高剂量MT组血糖值无明显变化(P0.05);与模型组比较,低剂量MT组和高剂量MT组心肌组织中MDA含量明显降低,CAT和GSH-Px含量明显升高(P0.05);HE染色显示低剂量MT组和高剂量MT组心肌结构损伤程度均较模型组轻;与模型组比较,低剂量MT组和高剂量MT组心肌组织中AGE和RAGE蛋白表达明显降低(P0.05)。结论 MT可以降低糖尿病大鼠心肌组织MDA含量,提高CAT和GSH-Px含量;可改善心肌结构变化;降低心肌中AGE和RAGE蛋白的表达。     

茜草多糖对半乳糖致衰老小鼠心肌线粒体能量代谢影响的研究

目的　研究茜草多糖对半乳糖致衰老小鼠心肌线粒体能量代谢的影响。方法　以D 半乳糖致衰老模型小鼠 ,观察茜草多糖对心肌线粒体呼吸链酶复合体Ⅰ、Ⅰ Ⅲ、Ⅱ Ⅲ的活性 ,H ATP酶的活性 ,Mn2 超氧化物歧化酶 (Mn2 SOD)活性以及丙二醛 (MDA)含量的影响。结果　茜草多糖可提高衰老小鼠心肌线粒体呼吸链酶复合体Ⅰ、Ⅰ Ⅲ、Ⅱ Ⅲ、H ATP酶及Mn2 SOD的活性 ,并能降低老年组MDA含量。结论　茜草多糖能减轻线粒体过氧化损伤 ,通过抑制线粒体的脂质过氧化和改善呼吸链酶的活性达到延缓衰老的作用。     

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.     

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.     

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.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.