增殖分化视角下成年哺乳动物心肌再生研究进展

心肌再生是逆转心肌损伤和心力衰竭的理想途径，也是心血管医学领域的研究重点。传统观点认为成年哺乳动物心肌细胞无法自我更新和再生，然而最近研究报道心肌细胞能以微弱比例内源再生。通过调节心肌再生过程或调控关键分子表达，可以诱导具有收缩功能的心肌细胞出现，改善损伤心脏的结构和功能。近年心肌再生研究大多侧重细胞增殖，对心肌细胞去分化、增殖及再分化的全过程关注较少。因此，该文从增殖分化视角综述成年哺乳动物心肌再生的诱导方式，旨在探讨实现成年哺乳动物心肌细胞大规模自我更新的可能性。     

钙网蛋白在心肌肥大中的研究进展

钙网蛋白（calreticulin,CRT）是内质网中主要的Ca^2＋结合分子伴侣,具有调控细胞Ca^2＋稳态、蛋白质合成与修饰等作用,参与调节细胞凋亡、应激、心血管炎症反应等多种生理和病理生理过程。CRT属于心脏胚胎基因家族,通过调节心肌细胞肌原纤维形成、促进糖原分解、诱导肥大相关基因转录、调节心脏传导系统发育及心肌细胞凋亡等,在心脏发育及心肌肥大的发生、发展过程起重要作用,本文对CRT在心肌肥大中的作用及其信号转导途径予以综述。     

钙网蛋白在心肌肥大中的研究进展

钙网蛋白(calreticulin, CRT)是内质网中主要的Ca2+结合分子伴侣,具有调控细胞Ca2+稳态、蛋白质合成与修饰等作用,参与调节细胞凋亡、应激、心血管炎症反应等多种生理和病理生理过程.CRT属于心脏胚胎基因家族,通过调节心肌细胞肌原纤维形成、促进糖原分解、诱导肥大相关基因转录、调节心脏传导系统发育及心肌细胞凋亡等,在心脏发育及心肌肥大的发生、发展过程起重要作用,本文对CRT在心肌肥大中的作用及其信号转导途径予以综述.     

心肌细胞肥大的信号转导通路

心肌肥厚是肥大刺激诱导核内基因异常表达的结果,细胞内信号转导通路是肥大刺激与核内基因转录活化的偶联环节。然而,淡同刺激诱导的心肌肥大可能具有不同的“分子表型”,这主要取决于它们启动的信号转导通路。对心肌肥大信号转导通路的深入认识,不仅胡助于阐明心肌肥厚的细胞分子机制,而且可为药物干预防治心肌肥厚提供新思路。     

U50488H、哌唑嗪及心得安对去甲肾上腺素诱导心肌肥大的作用比较

目的：观测κ阿片受体激动对去甲肾上腺素诱导心肌肥大的抑制作用,并与哌唑嗪、心得安作用进行比较。方法：结晶紫染色法测心肌细胞增殖程度;Lowry法测心肌细胞蛋白含量;计算机图象分析系统测心肌细胞体积;[3H]-亮氨酸掺入法测心肌细胞蛋白合成。结果：①低血清环境下,NE明显诱导心肌细胞蛋白含量、蛋白合成及体积的增加,但对增殖无影响。②哌唑嗪和心得安单独作用部分抑制NE诱导的心肌肥大;联合作用则完全抑制。③U50488H明显抑制NE诱导的心肌肥大;其抑制程度与哌唑嗪和心得安联合作用类似,明显高于二者单独作用。结论：NE通过激动α1-和β-肾上腺受体途径诱导心肌肥大。κ阿片受体激动显著抑制NE诱导的心肌肥大,这可能与干预α1-AR和β-AR途径有关。     

心肌细胞增殖影响因素和评价方法

大量心肌细胞丢失是心肌梗死后进展为心力衰竭和临床死亡的主要原因.近年来的研究证明,成年哺乳动物心肌具有一定的再生能力,但该能力十分有限而不足以修复受损的心脏组织,因此促进内源性心肌再生是未来治疗心肌梗死的重要方向.原有心肌细胞的增殖是内源性心肌再生的主要来源,因而探索心肌细胞增殖的调控机制,寻找促进心肌细胞增殖的干预措施成为心肌再生研究领域的热点,并取得显著进展.同时,成年心肌细胞具有可多倍体化、多核化但难以胞质分裂等特点,导致评估心肌增殖的方法成为难题,精确量化心肌增殖的各种模型和体系不断被开发.本文回顾总结了心肌再生的基本方式、心肌细胞增殖影响因素和评估方法,探讨了当前内源性心肌再生研究领域的进展和挑战.     

介导心肌肥大的一条新的信号通路--Calcineurin通路

心肌肥大是心肌细胞对外界刺激,如工作负荷、神经体液因子及内在心肌蛋白遗传突变一种基本应答。已知胞内Ｃａ＾２＋浓度升高在各种刺激诱导心肌肥大的信号传递中起重要作用,但对Ｃａ＾２＋信号下游的传递机制一直不甚清楚。新近研究证实,由Ｃａ＾２＋活化的钙调神经磷酸酶（ＣａＮ）在心肌肥大的信号传递中起重要作用,基可能是Ｃａ＾２＋信号致肥大基因活化的偶联环节。抑制ＣａＮ活性可阻滞各种因素诱导的心肌肥大发生与发展,     

钙调神经磷酸酶依赖的信号通路在大鼠心肌肥大中的作用及调节

本工作在大体动物模型、细胞及分子水平上,对钙调神经磷酸酶（CaN)依赖的信号通路在大鼠豳肥大中的作用及其调节机制进行了研究。结果发现;（１）ＣaN信号通路参与血流动力学超负荷、心肌纤维化、旁／自分泌因子等诱导的心肌细胞肥大;（２）ＣaN信号通道参与血管紧张素Ⅱ(AngⅡ)及碱性成纤维细胞因子(bFGF)诱导的心肌细胞肥大和AngⅡ及bFGF刺激的心脏成纤维细胞增殖;（３）ＣaN通路与丝裂素活化蛋白激酶（ＭＡＰＫ）及蛋白激酶Ｃ（ＰＫＣ）信号途径可能存在相互关系;（４）ＣaN的活化依赖胞内Ｃa^2 浓度的持续升高,ＣaN的活化还受蛋白激酶磷酸化的调节,ＡngⅡ刺激心肌细胞ＣaNmRNA的表达显著增加,ＣaNmRNA本身的表达受Ｃa^2 信号及ＭＡＰＫ级联反应的调控。结论：Ｃa^2 -ＣaN信号通路介导心肌肥大的发生。     

心肌营养素-1及其信号转导

心肌营养素 1(Cardiotrophin 1,CT 1)是细胞因子IL 6家族成员,它能够诱导心肌细胞肥大,刺激心脏和神经细胞的存活,具有广泛的生物学作用.其生物活性通过多种信号转导途径实现.     

MLP参与心肌肥大发生过程与Calcineurin/NFAT信号通路有关

心肌肥大是心肌细胞面对多种病理刺激时的共同反应,以心肌细胞体积增大和胚胎期基因的重新表达为标志.心肌发育调控基因肌肉LIM蛋白(muscle LIM protein,MLP)的表达异常与心肌肥大有关.为研究MLP参与心肌肥大发生的分子机制,采用去氧肾上腺素（phenylephrine, PE）刺激大鼠原代培养心肌细胞,建立心肌细胞肥大模型,采用RNAi技术敲减MLP的表达,分析MLP与肥大信号通路钙调神经磷酸酶（calcineurin）/活化T细胞核因子（nuclear factor of activated T-cells, NFAT）的关系.结果显示, 原代培养的心肌细胞经一定浓度的PE刺激后细胞表面积增加,肥大标志蛋白ANP、BNP表达增高,并伴有MLP表达上调. RNAi方法敲减MLP的表达则明显抑制PE诱导的心肌细胞表面积增加和BNP表达增高,并且直接 影响NFAT的转录激活活性,提示MLP与心肌肥大的发生密切相关,并且可能是通过calcineurin/NFAT信号通路而参与心肌肥大的发生.     

强直性脊柱炎生物治疗的现状及新进展

强直性脊柱炎是一种以脊柱病变为主的慢性痫,累及骶髂关节,引起脊柱强直和纤维化,造成不同程度的眼、肺、肌肉、骨骼病变,属自身免疫性疾病。强直性脊柱炎的致病机制仍未完全明了,但在治疗方面,生物治疗策略取得了可喜的新经验,生物药物展现出良好的应用前景。,     

SUMO化修饰在NF-κB信号通路中的作用

小泛素相关修饰物（smallubiq uitin related modifier,SUMO）修饰是与泛素化修饰类似的蛋白质翻译后修饰,在细胞信号转导、核质运输与转录调控等方面发挥重要作用。核因子-κB（nuclear factor-κB,NF-κB）通路是公认的参与炎症和免疫反应的重要调节通路。近年来研究发现,SUMO通过各种机制广泛参与NF-κB信号通路的调节。研究两者的关系,可能为相关疾病的防治找到新的思路。     

微核糖核酸在相关疾病发生发展中的调节作用

微核糖核酸（miRNA）是一类长度为18～25个核苷酸的内源性非编码小RNA,在转录后基因调控中发挥功能。miRNA通过降解mRNA或抑制蛋白翻译的方式调节特异基因表达。miRNA在多种生物进程包括发育、代谢、增殖、分化和凋亡中起到关键作用。miRNA的表达变化与相应的多种人类疾病及其发生发展密切相关。阐明miRNA对疾病基因的调节作用及其分子机制,将为人类某些疾病的基因治疗提供新的思路。     

植物化学物与糖尿病的表观遗传调节

表观遗传(epigenetics)是指DNA序列不发生变化,但基因表达却发生了可遗传的改变。在细胞分裂时,表观遗传能影响正常基因的遗传表型,从而影响疾病发生。糖尿病是当今严重危害人类健康的疾病之一,许多营养物质与其发生有关系,其中,一些植物化学物能通过表观遗传机制影响糖尿病及其并发症的发生。本文就近年来与糖尿病有关的表观遗传机制的研究及与之有关的植物化学物的研究进展做一综述。     

植物居群的基因流动态及其相关适应进化的研究进展

生物自然居群间的基因流不但可以阻止遗传分化以维持物种的完整性,而且也能积极响应生物多样化的进程。理解与基因流相关的适应性进化及其内在机理将有助于我们更好地认识生物物种形成和多样化的原始动力以及真正原因。该文通过对植物种内和种间居群基因流动态进行讨论,阐述了近年来有关植物基因流动态的一些重要理论观念和研究进展,以期为相关领域动态及趋势研究提供参考。     

Chronobiological effects on exercise performance and selected physiological responses

Previous studies investigating the impact of circadian rhythms on physiological variables during exercise have yielded conflicting results. The purpose of the present investigation was to examine maximal aerobic exercise performance, as well as the physiological and psychophysiological responses to exercise, at four different intervals (0800 hours, 1200 hours, 1600 hours, and 2000 hours) within the segment of the 24-h day in which strenuous physical activity is typically performed. Ten physically fit, but untrained, male university students served as subjects. The results revealed that exercise performance was unaffected by chronobiological effects. Similarly, oxygen uptake, minute ventilation and heart rate showed no time of day influences under pre-, submaximal, and maximal exercise conditions. Ratings of perceived exertion were unaffected by time of day effects during submaximal and maximal exercise. In contrast, rectal temperature exhibited a significant chronobiological rhythm under all three conditions. Under pre- and submaximal exercise conditions, significant time of day effects were noted for respiratory exchange ratio, while a significant rhythmicity of blood pressure was evident during maximal exercise. However, none of these physiological variables exhibited significant differential responses (percent change from pre-exercise values) to the exercise stimulus at any of the four time points selected for study. Conversely, resting plasma lactate levels and lactate responses to maximal exercise were found to be significantly sensitive to chronobiological influences. Absolute post-exercise plasma norepinephrine values, and norepinephrine responses to exercise (percent change from pre-exercise values), also fluctuated significantly among the time points studied. In summary, these data suggest that aerobic exercise performance does not vary during the time frame within which exercise is normally conducted, despite the fact that some important physiological responses to exercise do fluctuate within that time period. Accepted: 18 August 1997     

根施甜菜碱对水分胁迫下烟草幼苗光合机构的保护

以烟草品种大黄金5210（抗旱性强）和中烟100（抗旱性弱）为材料,研究了水分胁迫对烟草叶片光合机构的影响,并通过根部施用甜菜碱的方法,探讨了甜菜碱对烟草光合机构的保护作用。结果表明：水分胁迫导致烟草幼苗光合机构损伤,表现在叶绿素含量、PSII光化学效率、希尔反应活力以及类囊体膜ATPase活性下降,且对抗旱性弱的中烟100损伤更加严重。外源甜菜碱处理减轻了水分胁迫对以上指标的降低程度,特别是对干旱敏感型烟草品种中烟100的效果更加明显。甜菜碱的这种保护作用可能与它能够维持叶片中各种抗氧化酶活性、减轻活性氧的积累、保护类囊体膜上各种色素蛋白的功能以及缓解水分胁迫对膜的破坏作用有关。     

棉铃虫的细胞色素P-450单加氧酶系与菊酯类杀虫剂抗药性的关系(英文)

细胞色素Ｐ－４５０单加氧酶系在昆虫抗药性中起重要作用。本文研究了棉铃虫抗性品系与敏感品系间细胞色素Ｐ４５０含量、对－硝基茴香醚Ｏ－脱甲基酶和艾氏剂环氧化酶的差异。结果表明：抗性品系中细胞色素Ｐ－４５０含量、对－硝基茴香醚Ｏ－脱甲基酶活性分别是敏感品系的１．７１倍和２．２１倍,而艾氏剂环氧化酶活性仅为１．３５倍。因此细胞色素Ｐ－４５０含量和对－硝基茴香醚Ｏ－脱甲基酶在棉铃虫抗菊酯品系中起重要作用。进一步讨论了不同抗性品系间抗性机制不同的原因。     

Effects of gradient and age on energy expenditure and fat metabolism during aerobic exercise at equal intensity in women

[Purpose]This study aimed to investigate the effects of gradient and age on energy expenditure and fat metabolism during aerobic exercise at equal intensity in women.[Methods] Thirty women in their twenties (n=15) and fifties (n=15) were enrolled. All subjects performed aerobic exercise on a treadmill for 10 min at 0% and 6% gradient repeatedly to elicit 50%, 60%, and 70% VO₂max.[Results]Energy expenditure and fat oxidation were higher during aerobic exercise at 6% of the gradient than at 0%, and there was no significant difference in carbohydrate oxidation in any age group.[Conclusion]Aerobic exercise at a 6% gradient was more favorable for fat oxidation than a 0% gradient in all age groups. In particular, in the case of women in their fifties, walking on a gradient of 6%, which is favorable for increasing fat oxidation, was more effective than walking on flat ground for preventing and reducing obesity. However, to examine the difference in fat oxidation among exercise intensities more accurately, exercise performed for longer than 30 min is required. Follow-up studies are required to investigate the effect of various gradients on physiological and metabolic characteristics when carrying out aerobic exercises for more than 30 min.     

Chronic cold exposure increases skeletal muscle oxidative structure and function in Monodelphis domestica, a marsupial lacking brown adipose tissue

Monodelphis domestica (Marsupialia: Didelphidae) was used as a model animal to investigate and compare muscle adaptation to exercise training and cold exposure. The experimental treatment consisted of four groups of animals: either warm or cold acclimation temperature and with or without endurance exercise training. Maximal aerobic capacity during a running VO2max test in the warm-exercised or cold-exposed (with or without exercise) groups was about 130 mL O(2)/kg/min, significantly higher than the warm-acclimated controls at 113.5 mL O(2)/kg/min. Similarly, during an acute cold challenge (VO2summit), maximal aerobic capacity was higher in these three experimental groups at approximately 95 mL O(2)/kg/min compared with 80.4 mL O(2)/kg/min in warm-acclimated controls. Respiratory exchange ratio was significantly lower (0.89-0.68), whereas relative heart mass (0.52%-0.73%) and whole-body muscle mitochondrial volume density (2.59 to 3.04 cm(3)) were significantly higher following cold exposure. Chronic cold exposure was a stronger stimulus than endurance exercise training for tissue-specific adaptations. Although chronic cold exposure and endurance exercise are distinct challenges, physiological adaptations to each overlap such that the capacities for aerobic performance in response to both cold exposure and running are increased by either or both treatments.