慢性肾脏病-矿物质和骨代谢紊乱导致血管钙化的分子机制研究进展

慢性肾脏病-矿物质和骨代谢紊乱(CKD-MBD)所导致的血管钙化是增加CKD患者发生心血管事件的独立危险因素。钙磷平衡的破坏、氧化应激的增加、钙化抑制剂的丢失、RANKL表达的增加等均被认为与CKD患者血管钙化的发生有关。此外,受损的骨质能够进一步扰乱血清钙磷和甲状旁腺激素水平,从而促进CKD患者发生血管钙化。磷结合剂和双膦酸盐类药物是目前治疗CKD-MBD所致的血管钙化是治疗的常用方法,可以改善骨质疏松以及血管钙化。本文就近年来CKD-MBD血管钙化发生机制的研究进展进行了综述。     

高血磷诱导慢性肾衰患者血管钙化作用机制

血管钙化是慢性肾病患者心血管疾病发生的主要原因,由于肾脏功能紊乱以及继发的内分泌调节紊乱,慢性肾病病人常常发生高磷血症。众多的研究表明,升高的血清磷能够直接作用于血管平滑肌细胞进而促进血管钙化。目前的研究显示,高磷能够通过诱导平滑肌细胞分化为软骨/成骨样细胞、促进细胞凋亡以及激活氧化应激和炎症反应等多方面促进血管钙化。本文主要综述高磷导致血管钙化机制的研究最新进展,以及控制患者血清磷对于防治血管钙化的效果。     

2 型糖尿病血管并发症发生机制及中药干预作用的研究进展

糖尿病血管并发症是导致糖尿病患者死亡的主要原因之一。许多糖尿病患者非常重视血糖的控制,而对于糖尿病血管并发症并未予 以足够的关注。随着中药研究领域的开展,人们发现中药在糖尿病慢性血管并发症的治疗中具有明显的优势。从糖脂代谢异常、胰岛素抵抗、 氧化应激以及肾素-血管紧张素-醛固酮系统异常等方面,综述2 型糖尿病血管并发症的发生机制,并简介中药针对各发病机制过程的干预 作用。     

Plin1~(-/-)小鼠高血压发生机制

正脂肪组织功能紊乱与高血压密切相关,其可能机制包括炎症、氧化应激、肾素-血管紧张素-醛固酮系统激活和自主神经兴奋等。Perilipin 1基因敲除小鼠(Plin1~(-/-))小鼠出现脂肪组织功能紊乱,研究人员通过监测不同周龄Plin1~(-/-)小鼠主动脉血压,明确其可发生早发高血压,并初步探讨其机制。     

CKD-5期肾病患者血清FGF-23水平与血管钙化的关系

为了探讨终末期肾病(ESRD)患者血清成纤维细胞生长因子23(FGF-23)水平与心血管钙化的关系。我们选取了2015年9月~2016年5月在我院各科室接受治疗的ESRD患者68例为实验组,选取46例健康成年人为对照组。使用超声和腹部X线平片对心血管和腹主动脉血管钙化情况进行评定,同时测量成纤维细胞生长因子23(FGF-23)、血清肌酐(Scr)、钙(Ca)、磷(P)、碱性磷酸酶(ALP)、总胆固醇(TC)、三酰甘油(TG)、血红蛋白(HB)、甲状旁腺激素(i PTH)各项指标的含量。ESRD组患者FGF-23水平高于对照组,差异有统计学意义(p0.05),ESRD组患者FGF-23水平与Scr、P、iPTH、ALP呈正相关(r=0.423~0.687),与Ca、TC、TG、HB无相关性(r=-0.014~-0.113)。钙化组患者FGF-23水平高于非钙化组,差异有统计学意义(p0.05)。ESRD患者血清FGF-23水平的升高与心血管钙化的发生发展密切相关。     

缺氧诱导因子在慢性肾脏病进展至终末期肾病中的作用机制

慢性肾脏病(chronic kidney disease,CKD)已经成为影响全球健康的难题，延缓其进展至终末期肾病(end-stage renal disease,ESRD)阶段是治疗CKD的重要目标。缺氧和缺氧诱导因子(hypoxia inducible factor,HIF)与CKD的发生和发展有着密切的联系，HIF表达的增加可以延缓CKD的进程，减少CKD并发症的发生。本文主要从CKD贫血、肾间质纤维化、炎症、血管钙化以及急性肾损伤方面论述了HIF在其中发挥的作用，旨在为延缓CKD进展至ESRD阶段提供新的靶点和思路，改善CKD患者的预后。     

外泌体调控血管钙化的研究进展

血管钙化是钙、磷等矿物质在血管壁的异常沉积,是一个主动的、活跃的、被高度调控的生物学过程,受到钙磷代谢紊乱、氧化应激、机械应力和炎症等多种因素的影响.作为胞间通讯的重要载体,外泌体已被证实与血管钙化的发生密切相关.一方面,外泌体可以通过在细胞间传递蛋白质、microRNAs等信息,促进血管平滑肌细胞发生成骨样表型转化以及矿物质沉积;另一方面,外泌体还可以诱导血管内皮细胞发生内皮-间充质转化,进而调控血管钙化的进程.但是,外泌体在内皮细胞和平滑肌细胞参与血管钙化进程中的具体作用及机制目前尚不完全清楚.本文就外泌体在调节平滑肌细胞的成骨样表型转化、矿物质沉积、microRNA转运以及内皮细胞的内皮-间充质转化中的作用进行了综述,以期为血管钙化的防治提供新思路.     

脂肪因子在慢性肾脏病血管钙化中的作用

慢性肾脏病(chronic kidney disease, CKD)是一种全球性的经济成本高的健康负担。慢性肾脏病首要的死亡并发症是心血管疾病(cardiovascular disease, CVD),而血管钙化是引起慢性肾脏病患者发生心血管疾病的主要原因。当体内的促钙化因子与抑钙化因子失衡时,会激活血管内皮细胞一系列反应,从而促进血管钙化。最近研究发现在慢性肾脏病血管钙化的发生、发展过程中,脂肪因子扮演着重要角色。本文对各种脂肪因子在慢性肾脏病血管钙化中的作用进行详细的阐述,希望可以为慢性肾脏病血管钙化的防治提供新思路。     

肾素-血管紧张素系统通过氧化应激机制参与血管反应性的调节

肾素-血管紧张素系统过度激活导致血管氧化应激损伤,进而影响血管功能.xanthine氧化酶、NAD(P)H氧化酶和脱耦联的NO合酶是血管组织中活性氧的主要来源.超氧化物阴离子和活性氧簇中的其他成分通过多种机制失活NO在心血管疾病的发生和发展中具有重要作用.随着对氧化应激损伤参与血管反应性调节机制的认识逐渐加深,有希望通过抑制氧化应激损伤改善血管内皮功能.     

ACEI/ARB 对糖尿病肺病的影响

近年来,糖尿病肺部病变越来越受到关注。研究发现糖尿病患者存在肺通气功能障碍、弥散功能障碍,易于发生肺纤维化、合 并感染等。这主要与糖尿病时炎症介质的参与,ACE 基因存在插入多态性,氧化应激损伤和抗氧化失衡等有关。目前研究发现血 管紧张素转换酶抑制剂（ACEI）/ 血管紧张素受体阻滞剂(ARB)对糖尿病肺炎、慢性阻塞性肺疾病、肺间质纤维化等肺损伤有保护 作用,这可能与ACEI具有调节免疫反应、减轻细胞因子水平、抗氧化应激损伤等机制有关。     

Changes in lactate dehydrogenase activity in chicken tissues in hyperthyreosis in ontogenesis

The lactate dehydrogenase activity in reactions of lactate oxidation and synthesis was studied in subfractions of the chicken brain, heart and liver at the embryonal, early postembryonal and adult stages of development after thyroxine administration. It has been shown that during embryogenesis thyroxine predominantly enhanced the rate of lactate oxidation in the mitochondrial tissues. A marked increase in the lactate synthesis was found in cytoplasm of the adult chicken tissues. Specificity of enzyme activity alterations was detected in the chicken brain during ontogenesis after thyroxine administration.     

Scurvy in capybaras bred in captivity in Argentine

In order to determine if the absence of vitamin C in the diet of capybaras (Hydrochoerus hydrochaeris) causes scurvy, a group of seven young individuals were fed food pellets without ascorbic acid, while another group of eight individuals received the same food with 1 g of ascorbic acid per animal per day. Animals in the first group developed signs of scurvy-like gingivitis, breaking of the incisors and death of one animal. Clinical signs appeared between 25 and 104 days from the beginning of the trial in all individuals. Growth rates of individuals deprived of vitamin C was considerably less than those observed in the control group. Deficiency of ascorbic acid had a severe effect on reproduction of another population of captive capybaras. We found that the decrease in ascorbic acid content in the diet affected pregnancy, especially during the first stages. The results obtained suggest that it is necessary to supply a suitable quantity of vitamin C in the diet of this species in captivity.     

Role for dopamine in malonate-induced damage in vivo in striatum and in vitro in mesencephalic cultures

Defects in mitochondrial energy metabolism have been implicated in the pathology of several neurodegenerative disorders. In addition, the reactive metabolites generated from the metabolism and oxidation of the neurotransmitter dopamine (DA) are thought to contribute to the damage to neurons of the basal ganglia. We have previously demonstrated that infusions of the metabolic inhibitor malonate into the striata of mice or rats produce degeneration of DA nerve terminals. In the present studies, we demonstrate that an intrastriatal infusion of malonate induces a substantial increase in DA efflux in awake, behaving mice as measured by in vivo microdialysis. Furthermore, pretreatment of mice with tetrabenazine (TBZ) or the TBZ analogue Ro 4-1284 (Ro-4), compounds that reversibly inhibit the vesicular storage of DA, attenuates the malonate-induced DA efflux as well as the damage to DA nerve terminals. Consistent with these findings, the damage to both DA and GABA neurons in mesencephalic cultures by malonate exposure was attenuated by pretreatment with TBZ or Ro-4. Treatment with these compounds did not affect the formation of free radicals or the inhibition of oxidative phosphorylation resulting from malonate exposure alone. Our data suggest that DA plays an important role in the neurotoxicity produced by malonate. These findings provide direct evidence that inhibition of succinate dehydrogenase causes an increase in extracellular DA levels and indicate that bioenergetic defects may contribute to the pathogenesis of chronic neurodegenerative diseases through a mechanism involving DA.     

SSTR5 ablation in islet results in alterations in glucose homeostasis in mice

Somatostatin (SST) peptide is a potent inhibitor of insulin secretion and its effect is mediated via somatostatin receptor 5 (SSTR5) in the endocrine pancreas. To investigate the consequences of gene ablation of SSTR5 in the mouse pancreas, we have generated a mouse model in which the SSTR5 gene was specifically knocked down in the pancreatic beta cells (betaSSTR5Kd) using the Cre-lox system. Immunohistochemistry analysis showed that SSTR5 gene expression was absent in beta cells at three months of age. At the time of gene ablation, betaSSTR5Kd mice demonstrated glucose intolerance with lack of insulin response and significantly reduced serum insulin levels. Insulin tolerance test demonstrated a significant increase of insulin clearance in vivo at the same age. In vitro studies demonstrated an absence of response to SST-28 stimulation in the betaSSTR5Kd mouse islet, which was associated with a significantly reduced SST expression level in betaSSTR5Kd mice pancreata. In addition, betaSSTR5Kd mice had significantly reduced serum glucose levels and increased serum insulin levels at 12 months of age. Glucose tolerance test at an older age also indicated a persistently higher insulin level in betaSSTR5Kd mice. Further studies of betaSSTR5Kd mice had revealed elevated serum C-peptide levels at both 3 and 12 months of age, suggesting that these mice are capable of producing and releasing insulin to the periphery. These results support the hypothesis that SSTR5 plays a pivotal role in the regulation of insulin secretion in the mouse pancreas.     

2018年中国植物科学若干领域重要研究进展

2018年中国植物科学继续呈现快速发展的态势, 我国科学家在国际植物科学主流学术刊物发表论文数量大幅增加, 取得了多项具有重要影响的成果。调控植物生长-代谢平衡实现可持续农业发展入选2018年度中国科学十大进展; 中国被子植物区系进化历史研究入选2018年度中国生命科学十大进展。以水稻为代表的农作物和果蔬等经济作物研究在国际上已呈现出明显的优势, 若干领域已从“追赶”状态跨越到“领跑”地位。该文对2018年中国科学家在植物科学若干领域取得的重要研究成果进行了概括性评述, 旨在全面追踪和报道当前中国植物科学领域的发展前沿和热点, 展示中国科学家所取得的杰出成就。