大气颗粒物致细胞损伤效应的分子机制

大气颗粒物(PM)是大气中各种具有不同化学组分的颗粒状物质的混合体。其中,空气动力学直径≤10μm和≤2.5μm的可吸入颗粒物(PM10和PM2.5)由于吸附有重金属、多环芳烃等有机物及细菌、病毒等有害成分,并能够通过呼吸系统进入体内,因此对人体健康具有极大的危害作用。流行病学研究数据显示,大气中PM含量增加会显著提高呼吸道和心血管疾病的发病率和致死率。因此,揭示PM诱导呼吸系统和心血管系统损伤的分子机制,对于制定相应防治策略、减低环境相关疾病的危害具有重要意义和医学价值。我们根据目前有限的研究线索,对PM诱导细胞损伤反应中涉及的氧化应激、内质网应激和炎性反应等机制做一综述。     

大气可吸入颗粒物造成肺损伤的NF-κB研究进展

NF-κB信号通路在大气可吸入颗粒物（PM10）对肺的损伤过程中起到重要的作用,但NF-κB信号通路参与的损伤机理尚不清楚。本文对NF-κB的结构与组成、颗粒物中NF-κB的激活因素、激活过程和抑制剂的相关研究等内容做简要综述。     

病毒感染与宿主细胞DNA损伤应答

病毒感染宿主细胞后,利用细胞内的营养物质和原料进行复制和增殖,同时能引起宿主细胞启动抗病毒免疫应答的防御机制。此外,近年来的研究还表明病毒感染能够引起宿主细胞的DNA损伤应答,该反应是细胞另一种防止病毒入侵的自我保护机制。同时发现,病毒在长期进化过程中形成了不同的机制来对抗宿主细胞的DNA损伤应答,从而消除细胞对其复制和繁殖产生的不利影响。因此,研究和阐述病毒感染后引起宿主细胞DNA损伤应答途径的机制,可使我们采取相应对策选择新的抗病毒靶点,从而有利于新型抗病毒药物的开发。     

高血糖加重脑缺血损伤机制的研究现状

脑缺血是引起人类死亡的一个重要原因,由于其发病的分子机制十分复杂,各种因子作用相互影响,且多数因子的作用同时存在损伤和保护两种机制,使得脑缺血的研究充满了困难。目前众多研究都证实高血糖对缺血脑组织有损害作用,并可能导致局部或广泛缺血后预后更差。本文依据近几年的实验,重点阐述了五种最新的高血糖加重脑缺血过程和预后损伤的机制假说,包括高血糖通过引起过量谷氨酸释放导致的Ca2^＋大量内流造成损伤、高血糖状态下造成氧化应激从而产生各种自由基对神经元造成损伤、炎症因子相关的损伤、高血糖相关的血液灌流的减少以及高血糖造成脑内酸中毒从而引起损伤。期望这些对机制的探讨能够上加深广大医药研究人员对高血糖加重脑缺血损伤的认识,帮助找到新的药物作用靶点和治疗手段,启发新的研究思路。     

大气污染对糖尿病前期及健康人群的心肺及代谢系统健康效应的前瞻性定组研究

大气污染物是心肺系统疾病的重要风险因子,然而其对代谢系统疾病(如糖尿病等)的影响尚不明确.我国大气污染形势严峻,糖尿病患病人口基数大,对应疾病负担严重,因而研究大气污染物暴露对糖尿病发病及病理进程影响机制十分必要.现有的研究证据对回答心血管异常疾病患者对于大气污染物是否易感,以及大气污染物是否会通过特定生物机制通路而加剧血糖代谢异常病理进程等问题仍存在不足.本研究组基于已有研究结果以及以往研究局限性,建立针对上述科学问题的前瞻性定组研究(SCOPE).本研究针对糖尿病前期及健康对照人群,通过1年间4次重复随访采样分析大气污染物的健康效应,对环境暴露及健康终点进行综合评价,并比较两组人群对大气污染响应的效应差异.健康终点评价方面,通过生物标志物测量血糖代谢异常、胰岛素抵抗、内皮功能损伤、系统性炎症等多种生物机制通路损伤.环境暴露方面,对颗粒物组分及粒径进行精细测量,同时加入个体水平暴露评价.本研究有助于深入探索大气污染物对心血管代谢异常人群的健康效应,及其对应的机制通路.     

SIRT6在缺血再灌注损伤中的作用机制及研究进展

缺血性损伤后恢复血液供应会导致缺血再灌注（ischemia reperfusion, IR）损伤,这会导致组织损伤进一步加剧。IR损伤伴随着一系列机制,包括谷氨酸兴奋性毒性、钙超载、氧化应激、炎症和细胞凋亡,最终导致细胞死亡。IR损伤过程均由Sirtuins家族调控,在Sirtuins家族中,特异性定位于细胞核中的SIRT6可以促进对DNA损伤和氧化应激的抵抗,抑制基因组的不稳定性,在代谢稳态中发挥作用,同时SIRT6在人重要脏器中处于高度表达状态。但SIRT6在IR损伤中研究较少,结合国内外最新的研究进展,对SIRT6在IR损伤中的作用进行了回顾性的总结和分析,希望对国内外学者对于SIRT6在IR损伤中的研究提供一些参考依据。     

哺乳动物卵母细胞的DNA损伤与修复研究进展

DNA损伤是影响配子发生和胚胎发育的关键因素之一。卵母细胞容易被各种内外源因素(如活性氧、辐射、化疗药物等)诱发DNA损伤。目前研究发现,对于各类DNA损伤,各发育阶段的卵母细胞能够做出相应的DNA损伤反应,通过复杂的机制对DNA进行修复或者启动细胞凋亡。相比于进入生长阶段的卵母细胞,原始卵泡卵母细胞更容易被DNA损伤诱导凋亡。DNA损伤不易诱导卵母细胞减数分裂成熟进程停滞,然而携带DNA损伤的卵母细胞的发育能力明显下降。在临床上,衰老、放疗和化疗是导致女性卵母细胞DNA损伤、卵巢储备降低和不孕的常见原因。为此,人们尝试了能够减轻卵母细胞DNA损伤和增强DNA修复能力的多种方法,试图保护卵母细胞。本文对哺乳动物的各发育阶段卵母细胞的DNA损伤与修复的相关研究进行了梳理和总结,并讨论了其潜在的临床价值,以期为生育力保护提供新的策略。     

增温对植物叶片和细根氧化损伤与防御特征及其相互关联影响的研究进展

叶片和细根是植物地上和地下部分中最敏感和活跃的部分,对森林生态系统的碳循环起着十分重要的作用。叶片和细根生理代谢特征及其相互关联的变化不仅反映植物在全球变暖背景下的生长状况,也揭示了植物面对环境胁迫的响应特征和适应策略,已经成为全球变化领域研究的热点和难点问题。国内外已开展了大量相关实验,从氧化损伤、抗氧化防御及代谢物的角度探讨了全球变暖条件下植物叶片和细根生理代谢的变化特征和响应机制。目前部分研究认为大气增温将促进叶片体内活性氧类物质的积累,对叶片产生氧化损伤,而对细根的损伤作用不明显,但也有部分研究认为细根受土壤增温的影响更大。总之,植物叶片和细根如何通过调整自身生理代谢特征和器官间的相互协作来响应气候变暖,以及这些响应的内在机制仍未得到充分研究。为此,该文系统综述了全球变暖背景下植物叶片和细根氧化损伤与抗氧化防御特征及其相互关联变化的研究进展,以期为植物对全球变暖的响应和适应机制研究提供参考,并认为今后还应开展以下几个方面的研究:(1)在种群和群落尺度上加强增温对植物氧化损伤与防御特征的研究;(2)结合地上地下物候特征研究增温对植物氧化损伤与防御特征的影响;(3)从更多植物生理指...     

紫外线-B辐射对植物DNA及蛋白质的影响

大气平流层中的臭氧衰减,导致太阳辐射中的紫外辐射量有明显的增加,其中UV-B辐射对植物会产生不同程度的影响。分子生态学理论认为,UV-B辐射对植物造成的损伤,首先伤害植物的生物大分子,即进行光化学修饰。本文就臭氧衰减对生态环境和植物的影响途径进行了讨论,重点论述了UV-B辐射对植物蛋白质合成的抑制和DNA的损伤修复途径。并应用分子生物学技术研究植物对UV-B辐射的抗性机理和DNA修复技术的前景进行了展望。     

紫外辐射的细胞生物学效应及其机制

地球表面的生物体会受到来自阳光紫外辐射的照射。两极臭氧层空洞的形成使地球表面的紫外辐射水平,特别是UVB的水平增加,进而对生物体的危害日益加重。因此,深入研究紫外辐射生物学效应的信号转导机制并阐明其损伤机制和生物体的反应机制等具有重要意义,也可为紫外辐射损伤防护的研究提供新思路。本文综述了本领域近年来的相关研究,从紫外辐射所致生物学效应的信号转导机制(包括对DNA的直接损伤作用、细胞膜激酶和非激酶受体通路、细胞质通路以及microRNA)等方面对紫外辐射的损伤机制进行了比较系统的阐述和总结。     

Impact of deer in lowland Britain on agriculture, forestry and conservation habitats

Probably in response to recent changes in habitat structure, populations of a number of species of deer are increasing both in numbers and in geographical distribution in lowland Britain. In the wake of this expansion there is increasing awareness and concern over damage to agriculture/horticulture and forestry, as well as damage to sensitive vegetation in conservation areas. Despite a perception that damage levels are rising, data that actually quantify the scale of impact by deer on lowland agriculture and forestry interests or conservation habitats are scarce. This review attempts to draw together such objective data as are available to assess more formally the actual impact of deer damage in these different contexts and the economic significance of damage caused. The review concludes with a brief consideration of implications for management. The majority of agricultural damage reported in England and Wales was due to Fallow, Red and Roe Deer; Muntjac were only implicated in a little horticultural damage where they are numerous. Most reports were of damage to pasture or cereals, with oilseed rape, nursery and orchard crops also frequently damaged. Because of fundamental differences in ecology and distribution, different species of deer were implicated in different types of damage, depending on feeding habit and distribution in relation to geographical patterns of crop-type. In a woodland context, Fallow, Red and Roe Deer were implicated in the majority of reported damage in lowland UK, which is most frequent in the north of England and lowest in Wales. Despite the apparent severity of damage caused to agriculture or forestry, the actual economic significance of such damage would appear in many cases to be negligible or small. Field crops frequently recover completely from such damage, and although woodland crops may be checked and quality of the timber may be reduced as a consequence of earlier browsing damage, losses may be far less than they first appear. This whole question of the true economic cost of deer damage needs further research. Deer damage to conservation habitats in England and Wales appears largely restricted to woodland; impact on heathlands, grasslands and wetlands is generally welcomed as helping to arrest invasion of scrub. Within woodlands, while concern is expressed in a small number of cases over losses of sensitive ground flora or suppression of natural regeneration, the major problem is in damage to coppice regrowth on sites where coppice management has been recently reintroduced.     

Leucocytosis as a marker of organ damage induced by chronic strenuous physical exercise

The effects of strenuous physical exercise on the serial changes in the haematological, biochemical and hormonal markers were investigated. A group of 14 soldiers, aged 24–36 years, took part in a military training course for about 13 weeks. After severe exercise stress, an increase (90%) in the number of peripheral blood leucocytes was observed. The degree of leucocytosis showed a close correlation with the values of some serum parameters, such as concentrations of aspartate aminotransferase (AST;r = 0.747), lactate dehydrogenase (LD;r = 0.748), blood urea nitrogen (r = 0.756), creatine kinase (CK;r = 0.637), manganese-superoxide dismutase (Mn-SOD;r = 0.508), alanine aminotransferase (ALT;r = 0.542) and uric acid (r = 0.538), and concentrations of urinary parameters, such as vanilmandelic acid (r = 0.429) and free cortisol (r = 0.437). The subjects showing prominent leucocytosis over 9500 cells · l^–1 exhibited a lower concentration of serum cholinesterase than those who showed milder leucocytosis. The serum Mn-SOD concentration was closely correlated with the serial changes in serum concentrations of AST, ALT, LD and CK, indicating exercise-induced muscle and liver damage. The change in peripheral leucocyte number was assumed to be diagnostically informative and may be a prognostic marker, reflecting organ damage and restoration after strenuous physical exercise.     

南方森林雨雪冰冻灾害的特征

近年来极端气候事件频发,各地的雨雪冰冻灾害受到广泛关注。极端的雨雪冰冻灾害作为一个重要的扰动因子,对森林生态系统造成重大影响,尤其是在中国冰雪天气少有发生的南亚热带地区。2008年1-2月中国南方遭受了一场低温雨雪冰冻综合性极端天气灾害,其持续时间长,影响范围广,对中国南方森林造成了严重的损害。国内对此次雨雪冰冻灾情概况、林木受损情况以及雨雪冰冻灾害程度的影响因素等方面开展了大量研究,而现有的研究对受损林木评定的标准主观、粗略不全或是概念混淆,造成各研究结果难以比较。为明晰分类标准及相关概念,本文在总结雨雪冰冻灾害发生的气候与生物学特点、整合前人研究结果的基础上,提出雨雪冰冻灾害中林木生理冻害分类标准以及林木机械损伤分类标准,为相关研究提供参考依据。同时,总结分析雨雪冰冻灾害中导致森林受损的各影响因素,并将众多的因素总结归纳为影响凝雪冰凌重量及林木自身抵抗力2个方面。最后,针对灾害的影响因素以及灾后森林易发生的次生灾害,提出灾后森林恢复与重建的建议。     

牙鲆胚胎冷冻损伤的观察

为了观察牙鲆胚胎在冷冻保存过程中的形态受损情况,将其浸入20%PM（20%丙二醇和20%甲醇1∶1的混合液）中平衡,并用程序化法和玻璃化法对其冷冻保存2h后解冻,用摄影显微镜记录其在抗冻剂里平衡时和冷冻保存后的形态。结果显示在平衡过程中胚胎卵膜出现凹陷（称为溶液损伤）,但可以恢复;在冷冻过程出现胞内冰损伤,是致命的;用程序化法冷冻保存的尾芽期胚胎卵膜和卵黄完好,胚体边缘受伤;用玻璃化法保存的尾芽期胚胎,卵膜和卵黄损伤较重,胚体损伤较轻;因此将玻璃化法和程序化法结合可以达到扬长避短的效果。     

Oxygen accelerates the accumulation of mutations during the senescence and immortalization of murine cells in culture

Oxidative damage is a causal factor in aging and cancer, but it is still not clear how DNA damage, the cellular responses to such damage and its conversion to mutations by misrepair or misreplication contribute to these processes. Using transgenic mice carrying a lacZ mutation reporter, we have previously shown that mutations increase with age in most organs and tissues in vivo . It has also been previously shown that mouse cells respond to oxidative stress, typical of standard culture conditions, by undergoing cellular senescence. To understand better the consequences of oxidative stress, we cultured mouse embryo fibroblasts (MEFs) from lacZ mice under physiological oxygen tension (3%) or the high oxygen tension (20%) associated with standard culture, and determined the frequency and spectrum of mutations. Upon primary culture, the mutation frequency was found to increase approximately three-fold relative to the embryo. The majority of mutations were genome rearrangements. Subsequent culture in 20% oxygen resulted in senescence, followed by spontaneous immortalization. Immortalization was accompanied by an additional three-fold increase in mutations, most of which were G:C to T:A transversions, a signature mutation of oxidative DNA damage. In 3% oxygen, by contrast, MEFs did not senesce and the mutation frequency and spectrum remained similar to primary cultures. These findings demonstrate for the first time the impact of oxidative stress on the genomic integrity of murine cells during senescence and immortalization.     

Comparison of the effects of melatonin and pentoxifylline on carbon tetrachloride-induced liver toxicity in mice

The purpose of the study was to determine whether along and in combination melatonin (MLT) and pentoxlfylline (PTX) exerted beneficial effects on histopathological changes and changes in oxidant and antioxidant systems in liver caused by CCl₄-induced liver toxicity in mice. Mice were randomly divided into six groups: control, olive oil, toxicity, MLT, PTX, PTX+MLT. MLT 10 mg/kg/day, PTX 50 mg/kg/day, and the same individual doses in MLT+PTX combination were given intraperitoneally to mice for 7 day. CCl₄ 0.8 mg/kg/day was administered on the 4th, 5th, and 6th days of therapy in all groups except the control and olive oil groups. In the toxicity group, increased concentrations of malondialdehyde (MDA) and lipid hydroperoxides (LOOH) and decreased glutathione peroxidase (GSH-Px) and catalase (CAT) activities were found compared to the control and olive oil groups (p < 0.05). Compared to the toxicity group, both the PTX group and the PTX+MLT group had decreased MDA and LOOH levels, whereas MLT reduced only LOOH levels (p < 0.01). MLT, PTX and MLT+PTX increased the GSH-Px and CAT activities compared to the toxicity group (p < 0.05). MLT increased CAT activity compared to PTX and MLT+PTX (p < 0.05). Superoxide dismutase enzyme activity did not change in any group (p < 0.05). Histopatholically, ballooning, degeneration, apoptosis, and bridging necrosis were seen in the toxicity group. MLT, PTX and MLT+PTX decreased the apoptosis and bridging necrosis (p < 0.01), and PTX and MLT+PTX decreased balloon degeneration compared to the toxicity group (p < 0.01). These results indicate that administration of PTX and MLT alone and in combination before onset of liver toxicity might prevent the oxidative damage by reducing oxidative stress and increasing antioxidant enzyme levels.     

Calibration of the comet assay for the measurement of DNA damage in mammalian cells

We used X-rays from a linear accelerator and from a low energy therapeutic source to calibrate the single cell gel electrophoresis (comet assay), a widely used method to measure DNA damage. γ-Rays from ⁶⁰Co, with known efficiency in inducing DNA breakage, were used as reference. Human lymphocytes and one murine tumour cell line, F10-M3 cells, were irradiated under different experimental conditions. A similar relationship between radiation dose and induced DNA damage was obtained with γ- and X-rays. A calibration curve was constructed to convert the comet assay raw data into break frequency. The median levels of DNA breaks and oxidative damage in circulating lymphocytes from healthy volunteers were calculated to be 0.76 and 0.80 breaks/10⁹ Da, respectively, (0.50 and 0.52 breaks/10⁶ bp). The values of oxidative DNA damage were in the same order of magnitude as those found by others with HPLC methods.     

Calibration of the comet assay for the measurement of DNA damage in mammalian cells

We used X-rays from a linear accelerator and from a low energy therapeutic source to calibrate the single cell gel electrophoresis (comet assay), a widely used method to measure DNA damage. γ-Rays from ⁶⁰Co, with known efficiency in inducing DNA breakage, were used as reference. Human lymphocytes and one murine tumour cell line, F10-M3 cells, were irradiated under different experimental conditions. A similar relationship between radiation dose and induced DNA damage was obtained with γ- and X-rays. A calibration curve was constructed to convert the comet assay raw data into break frequency. The median levels of DNA breaks and oxidative damage in circulating lymphocytes from healthy volunteers were calculated to be 0.76 and 0.80 breaks/10⁹ Da, respectively, (0.50 and 0.52 breaks/10⁶ bp). The values of oxidative DNA damage were in the same order of magnitude as those found by others with HPLC methods.     

Relationships between the lucerne flea, Sminthurus viridis (L.) (Collembola: Sminthuridae), and damage to lucerne

Abstract The effect of lucerne flea, Sminthurus viridis , on plant growth (stem length and leaf number) and damage (percentage of leaves damaged and the percentage reduction in leaf area in the top, mid and lower thirds of stems) was considered at 2-weekly intervals in three consecutive lucerne growth cycles, each with a different mode of attack. The data were analysed to progressively determine relationships leading to a proposal for plant-based thresholds for lucerne flea control. Lucerne flea affected each factor measured, with damage considered more appropriate for making control decisions than plant growth. Damage increased from the base of plants upwards and its effect on yield was carried over into subsequent growth cycles. Damage was significantly related to lucerne flea numbers ( P  < 0.001) in two growth cycles and was higher when large nymphs or adults were dominant in one of these cycles. Yield was closely and best related to the percentage of the total number of leaves damaged ( R ² = 81.3%). The percentage of leaves damaged was also related to loss of final yield estimated at 2 ( R ² = 81.3%), 4 ( R ² = 78.9%) and 6 ( R ² = 66.6%) weeks into the first growth cycle only. Direct damage in the other two cycles did not result in yield loss. The percentage of leaves damaged (± confidence intervals) equating to 5% increments in yield loss were estimated at 2, 4 and 6 weeks into the first growth cycle. These are proposed as damage or treatment thresholds for testing.     

压力波对听觉器官的致伤作用——Ⅰ.致伤部位和损伤特性

本工作用二十余种武器压力波源在不同暴露条件下对近二千只豚鼠进行了系统的致伤实验。结果表明,压力波暴露后致伤部位主要在中耳和内耳;即使压力峰值已高达190dBSPL,听觉中枢还未见有损伤迹象。中耳损伤和内耳损伤的程度都与压力波的强度有关,但两者并不平行,压力峰值大时压力波可以只损伤或主要损伤中耳,压力峰值不很大但重复发数较多或脉宽较大时,则可能只损伤或主要损伤内耳。在一定的条件下,中耳的损伤能缓冲压力波对内耳的冲击,从而减轻内耳的损伤。在中耳损伤或中耳、内耳混合损伤时,豚鼠的听力丧失并没有象在人的噪声性耳聋时(内耳损伤为主)常见的那种突出的高频选择性。