Owing to its richness and uniqueness in biological information as an independent organ unit, microvascular network provides the most important communication between live cells and outer environment as well as maintains the inner balance of the body (homeostasis). Being an attractive scientific field, microcirculation has drawn the attention of many basic and clinical investigators, who have uncovered and uncovering the once thought complicated puzzles via advanced techniques and analytical means.
Microvascular endothelium is one of the key proponents of microvessel, so called "the largest endocrine organ", playing critical role in physiological and pathophysiological processes.
Among many research units in this field, one of the ongoing projects in our institute is focusing on the stimulation and inhibition of Angiogenesis targeting on ischemic organ and tumor growth(slides show).
In 20th century, life science is becoming the rapidly developed field. Genomics is ranked one of the three giant systemic engineerings in the world. The closing date of ganomics is reaching us.95% of sequancing data is expected to be obtained in May 2000,and the whole genomic map will be completed in 2003. Lots of data will come with huge amount of unknown biological information, thus, bioinformatics, structural biology and functional biology are urgently desired.
How to find out the critical sequence?
Which kinds of genes Provide useful information?
What's the function of the encoded protein?
All these questions emerged the birth of a new subject_the functional genomics-Proteomics. As a newborn science, proteomics is most necessary in selecting new medicine, designing functional target of drugs and detecting the expression of disease-related protein.
The development of genomics and proteomics is leading the exploration of life essence into a multidimensional biological world.
Due to selective expression of proteins that are up regulated in microvascular network, molecutar heterogeneity,i.e. vascular individuality or vascular molecular address has been found in the microvessels of each disease-related organ, such as that of myocardial infarction, diabetics, tumor etc. So that it is worthy considering the possibility of treating the same disease on deferent patients with various stratagy-Translating microvascular individuality into rational therapeutics!
At the turn of new century with rapid development of life science, we, Asian microcirculation researchers, must refresh our minds at the position of post_genomics. We must modify our research direction in accordance with modern era using molecular biology as a sharp tool to investigat the unknown of microvascular diseases. However, Science always finds itself in an endless cycle. The effect of all the most advanced techniques on the physiological activities must be verified by functional detection.
The time is coming for establishment of Microvascular Medicine in Asia to face the unavoided challenge of present life science.
No strength could prevent the occurence of:
Microvascular molecular biology,
Microvascular Bioinformatics,
Microvascular Genomics,
Microvascular Proteomics, especially Functional Microvascular Medicine integrated with Asian traditional Medicine.
世界微循环研究领域的前缘正在向前推进,其范围也以加速度向外扩展,成为现代科学揭示生命系统分子水平奥秘的尖端学科,成为基础与应用的生物医学科学中不可缺少的一部分。使这一特殊领域得以进一步辉煌的重要原因,是因为微循环是遍布机体各部位的独立器官单位,信息独特而丰富,是活体细胞与外环境之间微妙的信息交流和物质交换的重要途径。从事基础与临床的科研工作者们在自己的研究实践中认识到了微循环的重要性并积极投身其研究中,利用分子生物学、细胞生物学、化学、物理和工程学的大量工具和分析手段,以研究微循环为突破口而揭开了在过去被认为非常复杂的许多难题。
人体全部大小血管的内表面都由内皮细胞构成。微血管管壁的主要部分之一便是内皮细胞,它构成人体内无处不到的微血管网络。据报道,成人体内的内皮细胞总面积约为1~7m2,重量约1公斤[1]。以往内皮细胞被看作是一种机械性的屏障结构,而当今微血管内皮细胞已被称为机体内“最大的内分泌器官“。细胞肽类、剪切应力、缺氧、自由基、氧化的脂质或病毒感染等都能激活内皮细胞的功能,并分泌一系列物质,如:NO(EDRF),Endothelin-(EDCF),Prostaglandin I2(PGI2)等等。而血管的扩张与收缩、血压的升高与降低、血液粘滞度的改变、出凝血、细胞粘附等,则是上述内分泌物质作用的表现和后果。许多研究结果提示:微血管自律运动的激活和抑制,微血管的增生和抑制也是上述内分泌物质调节的结果。上述平衡被打破,将导致多种脑心血管疾病。内皮细胞在动脉粥样硬化发病中的作用尤为重要。Ross于70年代提出的“损伤应答假设“(response-to-injury hypothesis)认为动脉粥样硬化发生的始动环节是持续或反复发生的内皮损伤。
近年来的研究揭示:微血管内皮细胞能表达多种细胞表面整合素(Integrin)家庭成员,如层连蛋白(Vitronectin)等, 可与细胞外基质蛋白粘合, 完成一系列生命活动。 微血管内皮细胞也表达层连蛋白受体,与沉淀在受损伤组织中的层连蛋白、纤维酶原(fibronogen)和血栓素(thrombin)等基质蛋白结合。层连蛋白受体的表达在细胞粘附、细胞迁移和伤口愈合过程中发挥重要作用。在小动脉、微动脉、前毛细血管、后毛细血管、微静脉、小静脉管壁中尚有不同密度的平滑肌细胞,两种细胞的功能与血管内川流不息的血液成份的性能交织在一起,互为因果,独立而相依,复杂而有序,协调地主宰着人体各器官的生命活动,以及整个机体的内外环境的平衡。
纵观近年来的世界医学大奖,其中有许多研究是在微血管领域进行的。1974年诺贝尔生理/医学奖得主之一,George Palade, 就是研究了内皮细胞内新合成蛋白转运到细胞外的机制。1998年的诺贝尔生理/医学奖得主,美国纽约州立大学健康科学中心Robert F. Furchgott(药理学家),潜心研究药物对血管的作用,但却经常得到相互矛盾的结果。他发现,同一种药物有时引起血管收缩而有时又使其扩张。Furchgott怀疑药物的不同作用依赖于血管内壁的内皮细胞是否受到损伤。1980年他完成了一项精巧独特的实验,证实乙酰胆碱仅在内皮完整的情况下具有舒张血管的作用。他得出以下结论:血管的扩张是由于内皮细胞产生一种未知的信号分子使得血管平滑肌细胞舒张。他称这种信号分子为EDRF,即内皮源性舒张因子。他的发现导致人们为确定这个因子孜孜探求。美国德克萨斯大学休斯敦医学院Ferid Murad(医学博士、药理学家),分析了硝酸甘油和相关的血管扩张物质的特性,并于1977年发现它们释放NO,这种气体可导致平滑肌细胞舒张。他被这种现象所吸引:即一种气体可以调节重要的细胞功能,并推测许多内源性因子如激素可能也是通过NO产生作用的。然而,当时没有实验证据支持这一想法。而美国加州大学洛山矶分校医学院Louis J. lgnarro(药理学家),参与了探求EDRF的化学实质的研究。他与Robert Furchgott共同及各自完成了大量的实验研究,并于1986年证明EDRF就是NO,由此揭示了Furchgott所提出的内皮源性因子的奥秘。当1986年6月Furchgorr和Ignarro在一次学术会议上发表了他们的结果之后,引起了世界各地实验室连续不断的广泛研究。这是首次发现一种气体可以作为生物组织的信号分子。这三位学者的研究都是在微血管领域进行的。以下简单介绍几项有关研究。
脑心功能与微循环
人们过去认为大血管在大脑血液循环中发挥主要作用。近年研究表明:大脑可能对微血管压力更为敏感,代偿性的神经体液调节机制的激活与脑微循环状态密切相关。
微循环研究所在瑞典卡洛琳斯卡研究院的跨国实验室的研究首次证明:微循环障碍是动脉粥样硬化症的早期病变,而且远在血脂增高之前就发生了。我们并证明这些障碍归因于氧<
