肾素-血管紧张素系统:新成员,新效应

肾素-血管紧张素系统（RAS）通过作用于心血管、肾脏、肾上腺，控制体液、电解质平衡以及动脉压，是机体重要的调控系统。经典的RAS主要成分有肾素、血管紧张素原（AGT）、血管紧张素Ⅰ（AngⅠ）、血管紧张素Ⅱ（AngⅡ）、血管紧张素转换酶（ACE）、血管紧张素受体1（AT1）、血管紧张素受体2（AT2R）。     

高血压血管外膜重构机制及药物干预研究进展

随着对高血压发病机理的深入研究和降压药物的迅速发展,控制患者血压水平多能达到,但高血压伴发靶器官损害的患病率和致残、致死率尚未得到控制。其中,靶器官损害的共同病理学基础一心脏、血管重构起关键作用。多年来,血管重构的研究集中于血管内膜细胞及中膜血管平滑肌细胞（VSMC）。近年研究显示,血管外膜在高血压血管重构中亦发挥重要作用,特别是外膜成纤维细胞（AF）在各种病理性损伤刺激下转化为肌成纤维细胞（MF）,     

肾素-血管紧张素系统(RAS)与血管老化

随着年龄的增长，血管发生了各种衰老变化。如血管结构的改变、管壁的增厚、血管内皮功能的低下等，血管的这些衰老变化改变了各种心血管疾病的病理生理机制，从而改变了疾病发生的阈值、严重程度和预后。因此，血管的老化是心血管疾病中一个重要的危险因素。近年来，随着血管紧张素转换酶抑制剂（CEI）及血管紧张素Ⅱ（AngⅡ）受体阻断剂在临床上的广泛应用。证明血管紧张素系统在促进心血管病病中起着非常重要的作用。除此之外，对血管紧张紊系统的各种生理病理作用的研究也证明其与血管老化有重要作用。大量研究发现，血管紧张索系统除了在维持血压和调节体液电解质平衡起重要作用外，还能激活调节许多与细胞生长（凋亡）、纤维化及炎症有关的物质表达的细胞，调节许多与血管病理生理有关的过程，包括血管细胞的凋亡，血管平滑肌细胞（VSMC）迁移，炎性反应及细胞外基质（ECM）重建等。所以，血管紧张素系统与血管增龄化的改变关系密切。     

血管内超声在兔主动脉血管成形术后再狭窄诊断中的应用

目的 探讨血管内超声（IVUS）对兔经皮腔内血管成形术（PTA）后动脉粥样硬化模型血管再狭窄的诊断价值.方法 采用30只高脂喂养—球囊损伤新西兰兔胸腹主动脉建立动脉粥样硬化及PTA后再狭窄模型,分别于PTA术时及术后1、3、6个月行主动脉血管造影及IVUS显像检查,观察血管腔形态、狭窄度以及两种检查的相关性.结果 与PTA术前比较,PTA术后6个月IVUS以及血管造影检测到腹主动脉管腔明显狭窄（P≤0.05或P≤0.01）,IVUS检测到狭窄度较动脉造影组更为明显（P≤0.05）.IVUS对钙化斑块、偏心性斑块的检出率明显高于血管造影（P≤0.05）.结论 IVUS可准确测量血管腔的狭窄程度,确定血管腔内斑块的性质.     

低能量红激光局部照射预防血管成形术后再狭窄的实验研究

目的评价低能量红激光局部照射对血管成形术后再狭窄的预防作用。方法对雄性新西兰白兔进行腹主动脉和髂动脉球囊拉伤（单纯拉伤组５０只）和拉伤后低能量密度的红激光局部照射（激光照射组５０只）。两组分别于术后３天、１周、２周、４周和８周分批进行血管病理形态学、氚标记胸腺嘧啶核苷（３ＨＴＤＲ）渗透实验和血管造影检查。结果血管拉伤后８周造影显示,激光照射组血管最小内径显著大于单纯拉伤组（Ｐ＜００５）;血管狭窄程度明显减低（Ｐ＜００５）;病理形态学分析表明,两组血管损伤程度相同,与单纯拉伤组相比,激光照射后血管内膜增生受到显著抑制,血管壁３ＨＴＤＲ渗透量减少,外弹力膜围绕面积增大,管腔狭窄程度明显减轻。结论低能量红激光局部照射可以显著减少血管成形术后再狭窄的形成。     

头颈部CTA对颈部动脉血管狭窄性病变的诊断价值及与DUS和DSA对比分析

目的与超声（DUS）、数字血管造影（DSA）诊断结果对比分析,评价CT头颈部动脉血管造影（CTA）对颈部动脉血管狭窄性病变诊断准确性、敏感性及价值。方法对50例有临床症状患者行颈部动脉血管MSC-TA检查,应用最大密度投影M IP,多平面重建MPR,容积重建VR,高级血管分析软件AVA,进行重建,采用NASCET标准测量血管狭窄程度,对比超声及DSA一周内诊断结果,分析头颈部CTA对动脉血管狭窄性病变诊断价值。结果 CTA对轻度血管狭窄性病变、中重度血管狭窄性病变（尤其是椎动脉狭窄性病变）敏感度较高,准确度较DUS更高,血管中重度狭窄与DSA结果基本相同,并且能跟检出DSA漏诊轻度血管狭窄;对血管壁斑块（尤其是钙化斑块）敏感度及准确度较DSA高,对较小斑块及血管内膜增厚性病变超声敏感度更高。结论颈动脉CTA作为一种无创性检查方法对颈动脉血管斑块及血管狭窄性病变诊断有重要价值和帮助,可以颈部动脉血管检查的首选和重要方法,超声和DSA检查可以有效互补。     

局部肾素—血管紧张素系统与糖尿病肾病

RAS在糖尿病肾病（DN）发生发展中的作用是确切的,特别是肾脏局部的RAS.肾脏存在RAS的所有成分,包括：肾素（renin）、血管紧张素原（angiotensinogen、AGT）、血管紧张素Ⅰ（AngⅠ）、血管紧张素Ⅱ（AngⅡ）、ACE、血管紧张素Ⅱ1型（ATl）受体.本将会探讨DN时此系统各个成份的变化.[第一段]     

内皮细胞凋亡与动脉粥样硬化

血管内皮功能障碍、结构受损及血管平滑肌细胞（VSMC）增生是动脉粥样硬化（AS）等血管疾病发生过程中的关键因素。一些危险因素导致内皮功能障碍和损伤启动的内皮细胞（EC）凋亡可能是AS的始动环节。血管内皮损伤诱发的VSMC增生是AS新内膜斑块形成的中心环节。     

ACE2-Ang-（1—7）-Mas轴：心血管疾病治疗的新靶点

肾素-血管紧张素系统（RAS）在哺乳动物心血管活动的调节中发挥了重要的作用。随着血管紧张素转化酶（ACE）2和血管紧张素1—7[Ang-（1-7）]特异性受体Mas的发现,形成了RAS中一个对心血管有益的新分支：ACE2-Ang-（1-7）-Mas轴。其中ACE2可以水解血管紧张素Ⅰ（AngⅠ）、血管紧张素Ⅱ（AngⅡ）生成Ang-（1-7）。Ang（1-7）则通过Mas受体拮抗AngⅡ的作用,引起血管舒张、抑制细胞增殖。这一新分支的发现为心血管疾病的治疗提供了新靶点。     

肾素-血管紧张素系统阻滞剂抗纤维化的研究进展

肾素-血管紧张素系统（RAS）在体内有多种生物学活性,包括在血管系统收缩血管、增加血容量和升高血压,在组织器官也有相应的活性。RAS 在心血管系统平衡和心血管疾病的发展中作用重大［1］。肾素转变为血管紧张素原（AGT）再转变为血管紧张素Ⅰ（AngⅠ）,然后在血管紧张素转换酶（ACE）的作用下转变为血管紧张素Ⅱ（AngⅡ）,促进血管收缩和醛固酮的释放。AngⅡ是整个 RAS 的核心,是整个 RAS 系统最主要的生物活性分子［1］。迄今为止,已经发现了4种血管紧张素的受体,即 AT1、AT2、AT3、AT4,AT1进一步分为 AT1a 和 AT1b,ATⅡ可以和 AT1和 AT2结合［2］。AT1介导了 AngⅡ的大部分作用,如收缩血管、升高血压、促进细胞增殖和炎症反应等,而对AT2我们则知之甚少。我们常见的血管紧张素受体拮抗剂（ARB）类药物,均是选择性 AT1阻滞剂。     

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.     

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.     

Variabilité des concentrations plasmatiques de l’angiotensinogène et risque d’hypertension artérielle chez le rat transgénique

Aim

Genetic polymorphisms of the human angiotensinogen gene are frequent and may induce up to 30% increase of plasma angiotensinogen concentrations with a blood pressure increase of up to 5 mmHg. Their role for the pathogenesis of human arterial hypertension remains unclear. High plasma angiotensinogen levels could increase the sensitivity to other blood pressure stressors.

Methods

Male transgenic rats with a 9-fold increase of plasma angiotensinogen concentrations and male non-transgenic rats aged 10 weeks were treated or not with NG-Nitro-L-arginine-methyl ester for 3 weeks in their drinking water (n = 3/group). Systolic blood pressure and body weight were measured at baseline and at the end of the study when left ventricular weight and ventricular expression of angiotensin I-converting enzyme and procollagen Iα1 were determined (polymerase chain reaction).

Results

At baseline, transgenic rats had +18 mmHg higher bood pressure and –8% lower body weight compared to non-transgenic rats (P < 0.05) without significant changes for the vehicle groups throughout the study (P > 0.05). NG-Nitro-L-arginine-methyl ester increased blood pressure, left ventricular weight and left ventricular weight indexed for body weight by +41%, +17.6% and +18.6% (P < 0.05) in transgenic and +25%, +5.3% and +6.7% (P > 0.05) in non-transgenic rats compared to untreated animals, respectively. Cardiac gene expression showed no differences between groups (P > 0.05).

Conclusion

Increased plasma angiotensinogen levels may sensitize to additional blood pressure stressors. Our preliminary results point towards an independent role of angiotensinogen in the pathogenesis of human hypertension and associated end-organ damage.     

Morphological and immunocytochemical heterogeneity of cultured pinealocytes from one-week-and two-month-old rats: Planimetric and densitometric investigations

Abstract: In vitro preparations of rat pinealocytes are widely used for biochemical analyses of signal transduction processes. This paper deals with morphological and immunocytochemical features of such preparations. Special attention was paid to the problems of whether pinealocytes represent a heterogeneous cell population and how such heterogeneity may develop during ontogeny. The investigations were performed with cells which were obtained from the pineal organ of one-week-and two-month-old rats, attached to synthetic peptide-coated coverslips or tissue culture chamber slides, and maintained under in vitro conditions overnight. The attached cells were then fixed with paraformaldehyde. These preparations yielded monolayers of spherical cells of different sizes; most cells were isolated, but some of them were aggregated and formed small clusters. On the average, the cells from the one-week-old animals were smaller than the cells from the two-month-old animals. Immunocytochemical demonstration of S-antigen, a pinealocyte-specific marker, showed that the majority of the cells from two-month-old animals were intensely or moderately labelled. Pinealocytes from one-week-old animals were less S-antigen immunoreactive. Only very few cells (less than 1% displayed glial fibrillary acidic protein (GFAP)-immunoreactivity. Planimetric investigations of the cell size and semiquantitative densitometric investigations of the intensity of the S-antigen immunoreaction revealed that (i) pinealocytes kept in vitro form a heterogeneous cell population, and that (ii) this heterogeneity increases during postnatal development from one-week-old to two-month-old animals. Two groups of pinealocytes can be distinguished based on their developmental fate: pinealocytes of one group grow dramatically, but show only a moderate increase in S-antigen immunoreactivity, and pinealocytes of the other group retain their size, but display a distinct increment in S-antigen immunoreacti vitv.     

Effects of pinealectomy and melatonin administration on certain indices of ovarian hyperplasia and/or hypertrophy in rats with both ovaries intact or after unilateral ovariectomy

Abstract: In earlier studies from other laboratories it was shown that melatonin decreased ovarian weight in rats and inhibited compensatory hypertrophy of the remaining ovary after unilateral ovariectomy. This study was designed to examine the influence of melatonin on certain indices of ovarian hyperplasia and/or hypertrophy in adult female rats with both ovaries preserved and with either an intact pineal gland or with the pineal gland removed (pinealectomy, PX) or, finally, in sham-PX animals. Similar studies were conducted on rats after unilateral ovariectomy, referring the examined parameters to the remaining intact ovary. The studies included mitotic activity of granulosa layer cells and corpus luteum cells, ovarian weight, ovarian cross-sectional area, cross-sectional area of the granulosa layer of all the Graafian follicles and the cross-sectional areas of the corpora lutea, visible on the ovarian cross-section. On the basis of results, we conclude that: 1) the effect of PX on the processes of ovarian hyperplasia and hypertrophy may vary; analogously, exogenous melatonin administration may influence ovarian hyperplasia and hypertrophy in different ways; 2) PX and exogenous melatonin may, under certain conditions, exert similar biological effects, even synergistic effects; 3) melatonin inhibits ovarian growth processes, while the effects of PX are variable; 4) the results indicate that in experiments performed on rats, with the use of two control groups, i.e., intact and sham-PX, melatonin effects on these two groups may differ.