肾脏中肾素-血管紧张素系统的生理和病理生理作用

肾脏中肾素-血管紧张素系统(RAS)在肾脏生理功能的调节中有重要作用.近年来,肾脏RAS的新成分及新作用机制不断被发现.转基因动物研究使肾脏血管紧张素Ⅱ(AngⅡ)在血压及水钠平衡调节中的作用进一步阐明;AngⅡ的非血流动力学作用已经确立;血管紧张素转换酶2(ACE2)及Ang 1～7对肾功能的调节作用也已得到认可.肾素/前肾素特异性受体、ACE的信号转导功能,以及AT1受体的转激活功能等,已成为肾脏生理科学研究的热点.这些研究对于人们认识肾脏局部RAS功能,探讨延缓慢性肾脏病的进展的治疗策略具有重要意义.     

β-CM7干预对糖尿病大鼠心肌肾素-血管紧张素系统的影响及其保护机制

本文旨在探究β-CM7对糖尿病大鼠心肌组织肾素-血管紧张素系统(Renin angiotensin system,RAS)的影响及其保护机制。32只雄性SD大鼠通过相应处理被分为正常对照组、模型对照组、胰岛素治疗组(3.7×10~(–8) mol/d)及β-CM7干预组(7.5×10~(–8) mol/d)。连续饲养30 d后,处死大鼠取心肌。β-CM7在干预糖尿病模型后,组织中AngⅡ含量显著降低,Ang1-7含量极显著升高;AT1受体和Mas受体mRNA表达均显著升高;ACE和ACE2的mRNA表达均显著升高,且酶活均显著升高。综上可得,β-CM7可以通过激活RAS的负性调节通路"ACE2-Ang1-7-Mas轴"显著抑制大鼠心肌ACE mRNA和蛋白的强表达,缓解AngⅡ对心肌组织的损伤,提示β-CM7抑制心肌损伤的作用可能与ACE/ACE2通路有关。     

有氧运动上调Agtr1a基因甲基化改善高血压肠系膜动脉ACE1-AT1R收缩轴功能

血管紧张素Ⅱ 1A受体(angiotensin Ⅱ type 1A receptor, AT1aR)是Ang Ⅱ的主要受体亚型。AT1aR基因(Agtr1a)启动子区DNA甲基化水平的变化是调控AT1aR表观遗传的重要机制。为明确运动是否通过调节Agtr1a基因启动子区甲基化水平而减弱ACE1-AT1R收缩轴功能,从而起到改善高血压血管功能的作用,本研究选用3月龄自发性高血压大鼠(spontaneously hypertensive rat, SHR)和正常血压对照组大鼠(Wistar-Kyoto, WKY),随机分为正常血压安静组WKY-C、正常血压有氧运动组WKY-E、高血压安静组SHR-C、高血压有氧运动组SHR-E,各组n=24。12周跑台运动结束后,有氧运动显著减低运动组大鼠血压和体重(P0.05);采用微血管环张力测定技术测定肠系膜动脉对去甲肾上腺素(norepinephrine, NE)、血管紧张素Ⅱ(angiotensin Ⅱ, Ang Ⅱ)的反应性。结果显示,有氧运动显著减弱高血压大鼠肠系膜动脉对血管收缩因子NE、AngⅡ的收缩反应(P0.05);高效液相色谱法(high performance liquid chromatography, HPLC)测定血浆中ACE1-AT1R收缩轴主要活性肽血管紧张素原(angiotensinogen, AGT)、AngⅡ的水平。结果显示,有氧运动显著减弱高血压大鼠肠系膜动脉对血管收缩因子NE、AngⅡ的收缩反应(P0.05);免疫印迹法和q-PCR技术测定肠系膜动脉ACE1、AT1R蛋白质和AT1aR的mRNA水平相对含量。结果显示,有氧运动显著降低高血压大鼠肠系膜动脉ACE1、AT1R蛋白质和AT1aR mRNA水平(P0.05);亚硫酸氢盐测序BSP法测定Agtr1a基因的启动子区甲基化水平。结果显示,有氧运动显著上调高血压大鼠肠系膜动脉Agtr1a基因启动子区甲基化水平(P0.05)。本研究表明,有氧运动通过上调高血压肠系膜动脉Agtr1a基因启动子区甲基化水平,即而减弱RAS系统ACE1-AT1R收缩轴功能,从而抑制高血压血管张力增高,缓解血压增高。     

血管紧张素转换酶2-血管紧张素1-7-Mas轴对血管作用的研究进展

血管紧张素转换酶2（ACE2）和Mas受体的发现使人们对肾素-血管紧张素（RAS）有了更全面的认识。ACE2可水解血管紧张素Ⅰ和血管紧张素Ⅱ直接或间接生成血管紧张素1-7（Ang 1-7）,并与高血压的形成密切相关。Ang 1-7主要通过Mas受体引起血管舒张、抑制细胞增殖。ACE2-Ang1-7-Mas轴的发现为RAS的研究、高血压等心血管疾病的防治和新药开发提供了新的思路和方向。     

自发性高血压大鼠心脏中ACE,AT1R,ACE2和MasR表达变化的研究

目的：通过观察血管紧张素转化酶（ACE）和血管紧张素转化酶2（ACE2）在Wistar-京都种大鼠（WKY）和自发性高血压（SHR）大鼠心脏组织中表达的差异,探讨ACE与ACE2在自发性高血压大鼠高血压形成中的作用。方法：自由饲喂14周龄WKY和SHR雄性大鼠一周后,用BSN-II多通道无创测压系统测定大鼠收缩压（SBP）、舒张压（DBP）、心率（HR）并称重;放免法测定血浆中血管血管紧张素Ⅱ（AngII）含量;Real-time PCR测定心脏组织中ACE,ATI受体（ATIR）,ACE2和Mas受体（MasR）mRNA的表达水平;Western blot法检测心脏组织中ACE2的蛋白表达。结果：SHR大鼠SBP和DBP均显著高于WKY大鼠（P〈0.01）;两组大鼠心率和体重无显著差异（P〉0.05）;SHR大鼠血浆中AngII含量显著升高（P〈0.05）;与WKY大鼠相比,SHR大鼠心脏中ACE mRNA表达均显著升高（P〈0.05）,ACE2的mRNA和蛋白表达水平均显著下降（P〈0.05）;心脏组织中AT1R和MasR的mRNA表达没有显著性变化（P〉0.05）。结论：ACE与ACE2表达失调是SHR大鼠高血压形成的主要原因之一,其机理可能与局部组织RAS系统ACE-AngII-AT1R通路过度活跃,ACE2-Ang（1-7）-MasR通路相对不足有关。     

ACE2及其特殊功能

血管紧张素转换酶2（angiotensin—converting enzyme 2,ACE2）是新发现的与血管紧张素转换酶（ACE）相关的羧肽酶,在肾素-血管紧张素系统（rennin-angiotensin system,RAS）中ACE2可以使AngⅡ转换为Ang1-7,从而产生与血管紧张素Ⅱ相反的效应,同时ACE2还可使Ang I转换为Ang1-9。研究发现：ACE2与高血压、SARS以及肾脏、生殖等系统的疾病有着密切的关系。     

血管紧张素II 1型受体相关蛋白研究进展

血管紧张素Ⅱ(angiotensin Ⅱ,AngⅡ)作为肾素-血管紧张素系统(renin-angiotensin system,RAS)的关键效应因子,与血管紧张素Ⅱ1型受体(angiotensin Ⅱ type 1 receptor,AT1R)结合后,在体内发挥维持体液及电解质平衡、收缩血管、调节血压,促进心肌、肾近端小管以及血管平滑肌细胞增殖,参与肿瘤的发生发展、血管形成和转移等重要作用。最新研究发现,AT1R相关蛋白特异性作用于AT1R蛋白的碳末端,通过调节受体的内化、细胞膜的再通和受体的敏感性对其表达进行控制,发挥相应的生物学作用。本文的重点在于对AT1R相关蛋白的研究进展进行综述,阐述不同AT1R相关蛋白在RAS系统中所起的作用,为RAS系统的进一步研究提供依据。     

肾素-血管紧张素系统的新调节分子:ACE2

血管紧张素转化酶（angiotensin—converting enzyme,ACE）为含锌的金属蛋白酶,是肾素-血管紧张素系统（renin—angiotensin system,RAS）重要的调节分子。血管紧张素转化酶2（angiotensin—con—verting enzyme2,ACE2）是迄今发现的唯一的ACE同系物（homologue）,它主要分布于睾丸、肾脏和心脏。ACE2可水解血管紧张素Ⅰ（angiotensinⅠ,AngⅠ）和血管紧张素Ⅱ（angiotensinⅡ,AngⅡ）羧基端的1个氨基酸残基,分别形成Ang1-9和有血管舒张作用的Ang1-7。ACE2的生理病理作用还不甚明了,传统的ACE抑制剂不能抑制ACE2的活性。ACE2在心血管、肾脏系统的作用可能与ACE相反．与ACE共同调节心脏、肾脏等脏器的正常功能。     

闭锁卵泡中肾素—血管紧张素质系统的变化

目的：探讨卵巢局部的肾素－血管紧张素系统（RAS）在卵泡闭锁中的作用。方法：应用卵巢细胞双室培养,放射免疫测定（RIA）及免疫组化方法研究猪卵巢的健康卵泡和闭锁卵泡的颗粒细胞和卵泡内膜细胞与RAS的关系;观察了血管紧张素Ⅱ（AngⅡ)拮抗剂Saralasin及血管紧张素转换酶（ACE）抑制剂Captopril的作用。结果（1）与健康卵泡相比较,闭锁卵泡的卵泡液及卵泡内膜细胞培养液中的AngⅡ浓度明显升高,肾素浓度则明显降低;而颗粒细胞培养液中的AngⅡ和肾素浓度均无明显改变;（2）闭锁卵泡切片的AngⅡ,2型血管紧张素Ⅱ受体（AT2）染色明显强于健康卵泡;AngⅡ和AT2水平在双室培养的闭锁卵泡的卵泡内膜细胞中明显强于健康卵泡的卵泡内膜细胞;健康和闭锁卵泡的颗粒细胞中的AngⅡ,AT2水平变化不大;（3）双室培养中加入Saralasin或Captopril培养48h后,（a)与健康卵泡相比,闭锁卵泡的卵泡内膜细胞培养液中的AngⅡ浓度显降低,肾素浓度明显升高;（b)健康和闭锁卵泡的卵泡内膜细胞AngⅡ和AT2免疫组化染色均呈现下降,（c)RIA结果显示,健康和闭锁卵泡的颗粒细胞培养液中的AngⅡ和肾素浓度无明显变化;免疫组化结果显示,颗粒细胞的AngⅡ,AT2水平亦无显改变。结论：卵泡闭锁与卵巢RAS密切相关,AngⅡ和AT2是卵泡闭锁的重要相关因子;卵泡闭锁过程中卵巢局部的RAS变化主要发生在卵泡内膜细胞;Saralasin和Captopril可能通过调节卵巢RAS而具有抑制卵泡闭锁的作用。     

肾素-血管紧张素系统与糖尿病心肌病关系的研究进展

糖尿病时,肾素-血管紧张素系统(renin-angiotensin system,RAS)被激活,升高的血管紧张素Ⅱ(Ang Ⅱ)通过细胞表面的AT1受体,刺激心肌成纤维细胞增生及胶原代谢改变,引起心脏结构重塑,导致心肌间质及血管周围纤维化,胶原含量增多和排列紊乱,造成心室肌僵硬而影响舒张功能,出现糖尿病心肌病(diabetic cardiomyopathy,DCM)的临床症状.本文从RAS的主要成分Ang Ⅱ、Ang-(1-7)、Ac-SDKP和血管紧张素受体(ATR)与内皮素、活性氧、转化生长因子-β1、核因子-κB、信号转导系统以及细胞凋亡之间的相互作用,阐述RAS在糖尿病心肌病发生发展中所起的重要作用.     

Recent advances in the study of Kaposi's sarcoma-associated herpesvirus replication and pathogenesis

It has now been over twenty years since a novel herpesviral genome was identified in Kaposi's sarcoma biopsies. Since then, the cumulative research effort by molecular biologists, virologists, clinicians, and epidemiologists alike has led to the extensive characterization of this tumor virus, Kaposi's sarcoma-associated herpesvirus(KSHV; also known as human herpesvirus 8(HHV-8)), and its associated diseases. Here we review the current knowledge of KSHV biology and pathogenesis, with a particular emphasis on new and exciting advances in the field of epigenetics. We also discuss the development and practicality of various cell culture and animal model systems to study KSHV replication and pathogenesis.     

The structure, reproduction and taxonomy of Vidalia and Osmundaria (Rhodophyta, Rhodomelaceae)

Comprises species occurring mostly in subtidal habitats in tropical, subtropical and warm-temperate areas of the world. An analysis of the type species, V. spiralis (Sonder) Lamouroux ex J. Agardh, a species from Australia, establishes basic characters for distinguishing species in the genus. These characters are (1) branching patterns of thalli, (2) flat blades that may be spiralled on their axis, (3) width of the blade, (4) primary or secondary derivation of sterile and fertile branchlets and (5) position of sterile and fertile branchlets on the thalli. Application of the latter two characters provides an important basic method for separation of species into three major groups. Osmundaria , a genus known only in southern Australia, was studied in relation to Vidalia , and its separation from the Vidalia assemblage is not accepted. Species of Vidalia therefore are transferred to the older genus name, Osmundaria. Two new species, Osmundaria papenfussii and Osmundaria oliveae are described from Natal. Confusion in the usage of the epithet, Vidalia fimbriala Brown ex Turner has been clarified, and Vidalia gregaria Falkenberg, described as an epiphyte on Osmundaria pro/ifera Lamouroux, is revealed to be young branches of the host, Osmundaria prolifera.     

New or rare chromosome counts in Artemisia L. (Asteraceae, Anthemideae) and related genera from Kazakhstan

Fifteen chromosome counts of six Artemisia taxa and one species of each of the genera Brachanthemum, Hippolytia, Kaschgaria, Lepidolopsis and Turaniphytum are reported from Kazakhstan. Three of them are new reports, two are not consistent with previous counts and the remainder are confirmations of very scarce (one to four) earlier records. All the populations studied have the same basic chromosome number, x = 9, with ploidy levels ranging from 2x to 6x. Some correlations between ploidy level, morphological characters and distribution are noted.     

肝癌中HBV和HCV基因和抗原的分布及意义

采用原位分子杂交方法检测HCV RNA及HBV X基因;采用免疫组织化学方法研究HCV核心抗原,非结构区C33c抗原及HBxAg在肝细胞肝癌中的定位及分布.结果表明(1)HCV RNA、HBV X基因在肝细胞肝癌组织检出率分别为40%(55/136)和82%(112/136).HCV RNA定位于癌细胞的胞浆内,阳性细胞呈散在、灶状及弥漫分布三种形式;HBV X基因在肝癌细胞中的分布呈胞浆型、核型及核浆型,阳性细胞也呈上述三种分布形式;(2)HCV C33c抗原、核心抗原在肝细胞肝癌中的阳性率为81%(133/164)及86%(141/164).C33c抗原定位于癌细胞及肝细胞的胞浆内;核心抗原既定位于癌细胞核中,又可定位于胞浆中.C33c抗原阳性细胞以灶状分布为主;而核心抗原阳性细     

Selection with two alleles and complete dominance

For a plant selection model with frequency-independent viabilities, fertilities and selfing rates, it is shown that apart from global fixation, for certain parameter combinations a protected polymorphism and facultative fixation (either allele may become fixed according to initial frequencies) may both occur. Facultative fixation requires different selling rates for the dominant and recessive type. Protection of the polymorphism requires resource allocation for male and female function. In this connection the problem of purely genetically caused population extinction is discussed.
For general frequency dependence and regular segregation, the chances for establishment of a completely recessive gene are compared to those of a completely dominant gene. It is proven that the process of establishment of the recessive gene, despite a fitness advantage, may be considerably endangered by drift effects if random mating prevails. The recessive gene may reach the same effectivity in establishment as a dominant gene, only if the recessive homozygote mates exclusively with its own type during the period of establishment.