Vasoconstriction: a new activity for platelet-derived growth factor

Platelet-derived growth factor (PDGF) is a potent mitogen for vascular smooth muscle cells that has been implicated in the pathogenesis of atherosclerosis. The potential role of PDGF in the altered vasoreactivity of atherosclerotic vessels has been studied through an examination of its effects on contractility in the rat aorta. PDGF caused a concentration-dependent contraction of aortic strips and was significantly more potent on a molar basis than the classic vasoconstrictor peptide angiotensin II. Furthermore, PDGF increased the cytosolic free calcium concentration in cultured rat aortic smooth muscle cells. These observations suggest a new biological activity for PDGF that may contribute to the enhanced vasoreactivity of certain atherosclerotic vessels.     

拳参-413对大鼠离体胸主动脉环的舒张作用机制研究

[目的]研究拳参-413对大鼠离体胸主动脉血管的舒张作用机制。[方法]采用离体血管环灌流方法观察拳参-413在含Ca+或无Ca+的Krebs液孵育条件下对去甲肾上腺素(NA)引起的血管平滑肌收缩的影响,考察拳参-413舒张血管作用的时间依赖性,并观察拳参-413对浓度40和80 mmol/L的KCl引起的血管平滑肌收缩的影响。[结果]拳参-413能舒张NA引起的血管收缩,且呈浓度依赖性;拳参-413(100μmol/L)在30 min达到最大舒张效应;无Ca+组拳参-413抑制NA所致血管平滑肌收缩效应大于含Ca+组;拳参-413对浓度40和80 mmol/L的KCl引起的血管平滑肌收缩均有抑制作用,且两者量效曲线明显上移。[结论]拳参-413可舒张血管平滑肌,其作用机制可能与该药促进NO合成释放,开放钙激活的钾通道以及抑制血管平滑肌细胞外钙内流和内钙释放有关。     

五节芒茎秆微观构造及结晶度研究

 为更好地研究和利用五节芒Miscanthus floridulus茎秆,并为五节芒工业化利用奠定基础,研究了五节芒茎秆微观构造及茎秆去髓原料的纤维素相对结晶度。结果表明：五节芒茎秆皮部为茎秆最外层不含维管束的部分,木质部为皮部内圈维管束较多且紧密分布的部分,髓部为茎秆中部呈白色、含少量维管束的部分。茎秆表皮层由表皮膜、长细胞、短细胞和气孔器构成,长细胞长边边缘多呈锯齿形,且长、短细胞内含硅质。维管束由木质部、韧皮部、纤维细胞组成。原生木质部含环纹导管或螺纹导管。后生木质部的导管类型有网纹导管和孔纹导管。基本组织薄壁细胞主要特点是壁薄, 壁上有纹孔,且内含淀粉粒。五节芒去髓茎秆梢部纤维相对结晶度为43.21%,中部为42.08%,基部为44.49%,基本相似,没有表现出明显的规律性。图2 表1参15     

高山兀鹫的食管组织学观察

应用大体解剖技术、H.E染色法,观察了高山兀鹫食管组织学结构并与家禽和哺乳动物的食管比较。结果表明:高山兀鹫的食管上段皱襞很少,而下段则形成很多皱襞;食管黏膜上皮为复层扁平上皮,角质化明显;黏膜肌层由分散的平滑肌束构成;食管上段黏膜下层内食管腺丰富,而下段食管腺很少;食管肌层分为两层:纵肌和环肌,食管下段比上段的肌层发达;食管外膜是一层薄的纤维层,内含血管、神经。     

Purification and sequence analysis of bioactive atrial peptides (atriopeptins)

Mammalian cardiac atria have several biologically active peptides that exert profound effects on sodium excretion, urine volume, and smooth muscle tone. In the present study two such peptides of low molecular weight were purified and separated from each other on the basis of differences in charge, hydrophobicity, and biological profile. The first peptide, designated atriopeptin I, exhibits natriuretic and diuretic activity and selectivity relaxes intestinal smooth muscle but not vascular smooth muscle strips. The second peptide, atriopeptin II, is a potent natriuretic and diuretic that relaxes both intestinal and vascular strips. Sequence analysis of atriopeptin I indicates that it is composed of 21 amino acids, of which serine and glycine residues predominate. The amino terminal sequence of atriopeptin II up to residue 21 is the same as that of atriopeptin I, with the addition of the Phe-Arg extension at the carboxyl terminus. Both peptides appear to be derived from a common high molecular weight precursor (designated atriopeptigen); their biological selectivity and potency may be determined by the site of carboxyl terminal cleavage.     

新型大豆苷元萘磺酸酯的合成

为了提高大豆苷元抑制血管平滑肌细胞异常增殖活性,利用药动团变换原理对大豆苷元进行修饰,设计合成了一系列新型大豆苷元萘磺酸酯衍生物,为进一步抑制血管平滑肌细胞活性实验提供样品。从时间、温度、反应物配比、溶剂与催化剂配比、反应物与催化剂配比等5个方面优化了关键中间体2的合成工艺,所有化合物的结构均经IR、MS、~1H NMR和元素分析予以确证。     

Identification of monocyte chemotactic activity produced by malignant cells

Human malignant cells secrete low molecular size proteins that attract peripheral blood monocytes and may be responsible for the accumulation of tumor-associated macrophages observed in vivo. Similar chemotactic proteins are secreted by cultured vascular smooth muscle cells. The predominant monocyte chemoattractants produced by tumor cells of differing origin were demonstrated to be related to smooth muscle cell-derived chemotactic factor. Thus, a single class of chemotactic proteins is produced by different cell types, which suggests a common mechanism for the recruitment of monocytes and macrophages. These results are significant in view of the potential of macrophages to affect tumor growth.     

Vascular smooth muscle: quantitation of cell thickness in the wall of arterioles in the living animal in situ

The wall of microarterial vessels, in the living animal in situ, was examined at magnification up to x 6500 on the television screen. The optical resolution af the cell components of the wall was sufficiently clear to permit image formation and splitting for permanent recording and quantitation. Thickness of single smooth muscle cells at rest was estimated to be 2.08 microns (S.D. +/- 0.24 micron) and 2.78 microns (S.D. +/- 0.59 micron) by two different approaches. Changes in cell thickness during activity were also recorded and quantitated.     

家兔子宫内膜细胞和平滑肌细胞的分离培养及鉴定

为了建立一种高效的子宫细胞分离培养方法,用酶消化、过滤、离心与差速贴壁纯化相结合的方法分离培养家兔子宫细胞,分别以上皮细胞角蛋白、波形蛋白、α-平滑肌肌动蛋白等为抗原的免疫荧光对分离培养的细胞进行鉴定,并采用流式细胞仪分析细胞纯度。结果表明,家兔子宫内膜上皮细胞培养24 h后大部分贴壁,培养3 d左右形成单层细胞集落,呈角蛋白阳性,细胞圆形或椭圆形,胞质呈红色,核呈蓝色,纯度达96%以上;子宫内膜基质细胞培养0.5 h后即有贴壁,培养2 d后呈单层细胞集落状生长,呈波形蛋白阳性,细胞多边形或梭形,胞质呈红色,核呈蓝色,纯度达95%以上;平滑肌细胞培养24 h后大部分贴壁,6~7 d融合成片,呈α-平滑肌肌动蛋白阳性,细胞大都长梭形,胞质呈红色,核呈蓝色,纯度达98%以上。说明该方法能够成功分离并得到高产量、高纯度、高增殖能力的子宫内膜细胞及平滑肌细胞。     

Strontium accumulation by sarcoplasmic reticulum and mitochondria in vascular smooth muscle

Electron-opaque deposits of strontium were observed in the sarcoplasmic reticulum and in mitochondria of spontaneously contracting vascular smooth muscles that had been incubated in a strontium-containing solution prior to fixation. The deposits were present in those elements of the sarcoplasmic reticulum that are in close contact with the surface membrane and also in more centrally located portions. In vascular smooth muscle that does not contract spontaneously, similar deposits of strontium were only seen if the muscle was depolarized during or glycerinated before exposure to the strontium-containing solution. Strontium was also deposited in the sarcoplasmic reticulum of the endothelium. It is suggested that translocation of calcium from the sarcoplasmic reticulum that is in close contact with the surface membrane, and now shown to accumulate divalent cations, is responsible for the action potential-triggered contractions of rabbit and guinea pig mesenteric veins. Strontium may also be a suitable marker for identifying sites that accumulate calcium in other types of cells in which translocation of calcium plays a major regulatory function.     

eNOS基因转染对大鼠颈总动脉损伤后再狭窄程度的影响

为了研究eNOS基因转染对大鼠颈总动脉损伤后再狭窄程度的影响,以2F导管制作球囊损伤的大鼠颈总动脉内膜剥脱模型。用重组真核表达载体pcDNA3.1-eNOS经Fugene6介导体内转染大鼠的损伤后血管平滑肌细胞,2w、1m、2m后处死大鼠,取出大鼠的左侧颈总动脉及对侧正常的颈总动脉,分别应用HE染色和Verhoeff铁苏木精染色,观察血管再狭窄的程度,结果发现:体内eNOS转染组的血管内膜增生明显减弱,再狭窄程度显著低于体内空白对照组和空载pcDNA3.1(-)转染组(P<0.01)。而后二者之间无显著差异(P>0.05)。     

Fine structure of muscle cells of the human testicular capsule: basis of testicular contractions

Electron micrographs of human testicular capsule reveal large numbers of branching smooth muscle cells coursing through collagenous tissue of the tunica albuginea. These cells have subcellular morphology characteristic of smooth muscle cells, and they associate with one another through areas of close contact. These are the contractile cells responsible for spontaneous contractions of the human testicular capsule-contractions that may be important in transporting nonmotile sperm out of the testis.     

Regulation of myosin phosphatase by a specific interaction with cGMP- dependent protein kinase Ialpha

Contraction and relaxation of smooth muscle are regulated by myosin light-chain kinase and myosin phosphatase through phosphorylation and dephosphorylation of myosin light chains. Cyclic guanosine monophosphate (cGMP)-dependent protein kinase Ialpha (cGKIalpha) mediates physiologic relaxation of vascular smooth muscle in response to nitric oxide and cGMP. It is shown here that cGKIalpha is targeted to the smooth muscle cell contractile apparatus by a leucine zipper interaction with the myosin-binding subunit (MBS) of myosin phosphatase. Uncoupling of the cGKIalpha-MBS interaction prevents cGMP-dependent dephosphorylation of myosin light chain, demonstrating that this interaction is essential to the regulation of vascular smooth muscle cell tone.     

Shear-activated nanotherapeutics for drug targeting to obstructed blood vessels

Obstruction of critical blood vessels due to thrombosis or embolism is a leading cause of death worldwide. Here, we describe a biomimetic strategy that uses high shear stress caused by vascular narrowing as a targeting mechanism--in the same way platelets do--to deliver drugs to obstructed blood vessels. Microscale aggregates of nanoparticles were fabricated to break up into nanoscale components when exposed to abnormally high fluid shear stress. When coated with tissue plasminogen activator and administered intravenously in mice, these shear-activated nanotherapeutics induce rapid clot dissolution in a mesenteric injury model, restore normal flow dynamics, and increase survival in an otherwise fatal mouse pulmonary embolism model. This biophysical strategy for drug targeting, which lowers required doses and minimizes side effects while maximizing drug efficacy, offers a potential new approach for treatment of life-threatening diseases that result from acute vascular occlusion.     

植物天然活性产物调控血管平滑肌细胞表型转化研究进展

血管平滑肌细胞(vascular smooth muscle cells,VSMCs)是血管壁的主要构成组分。同时,VSMCs容易受到异常环境信号的影响,发生表型从收缩型向增殖型转化,从而导致以血管平滑肌细胞增生为特征的心血管疾病的发生及发展。因此,寻找调控VSMCs表型转化的天然活性物质,揭示其调控的分子机制非常重要。近年来的研究发现,多种植物天然活性产物可以调控血管平滑肌细胞表型转化,从而为筛选治疗心血管系统疾病的药物研发提供了基础。介绍了VSMCs的特性及其表型转化引起的相关心血管疾病,总结了调控VSMCs表型转化的植物天然活性产物,重点综述了近几年植物天然活性产物调控血管平滑肌细胞表型转化分子机制的研究进展。     

Localization of PDGF-B protein in macrophages in all phases of atherogenesis

Lesions of atherosclerosis occur in the innermost layer of the artery wall and consist primarily of proliferated smooth muscle cells surrounded by large amounts of connective tissue, numerous lipid-laden macrophages, and varying numbers of lymphocytes. Growth-regulatory molecules may be involved in intimal accumulation and proliferation of smooth muscle cells responsible for the occlusive lesions of atherosclerosis. Platelet-derived growth factor (PDGF) B-chain protein was found within macrophages in all stages of lesion development in both human and nonhuman primate atherosclerosis. Thus macrophages may play a critical role in the disease by providing PDGF, a potent chemotactic and growth-stimulatory molecule, to the intimal smooth muscle cells.     

Contraction of granulation tissue in vitro: similarity to smooth muscle

Strips of granulation tissue from three different experimental models contract in vitro when treated with substances that induce contraction of smooth muscle. Because the fibroblasts in such tissues have some ultrastructural features typical of smooth muscle, our findings indicate that fibroblasts are able to modulate toward a cell type that is morphologically and functionally close to smooth muscle.     

莱氏拟乌贼成体副缠卵腺超显微结构

通过组织学和透射电镜技术对莱氏拟乌贼副缠卵腺的超显微结构进行了研究。结果显示,副缠卵腺由腺壁组织、腺体小管和结缔组织组成,其中腺壁组织由柱状上皮细胞和肌肉细胞组成;腺体小管由单层上皮细胞环绕构成,上皮细胞内细胞器数量丰富,包括线粒体、内质网和高尔基复合体等,管道数量众多且排列紧密,在管腔中可见大量杆状细菌和上皮细胞的分泌物质,管腔内壁着生微绒毛和纤毛;腺体小管外充满结缔组织,其中分布着少量血管和肌纤维。分析认为,莱氏拟乌贼副缠卵腺属于分泌型腺体,分泌物质包括形成卵鞘的凝胶状物质和为共生菌提供营养的物质,共生菌来源属于“水平传递”,其分泌物质具有抗菌活性。     

Platelet-mediated cholesterol accumulation in cultured aortic smooth muscle cells

Cholesterol accumulates within smooth muscle cells and macrophages in atherosclerotic lesions, thereby contributing to the progressive enlargement of these lesions. The mechanism of this cellular accumulation of cholesterol is not known. The possibility that platelets may have a role in the cellular cholesterol accumulation that occurs during atherogenesis was investigated. Incubation of thrombin-activated washed rat platelets (or platelet-free supernatants prepared from thrombin-activated platelets) with cultured rat aortic smooth muscle cells induced cholesteryl ester lipid droplet accumulation within the smooth muscle cells. No cholesteryl ester lipid droplets accumulated when smooth muscle cells were incubated with unactivated platelets. Smooth muscle cell lipid droplet accumulation occurred in the absence of serum lipoproteins and was not inhibited by mevinolin, a drug that blocks cholesterol synthesis. These findings suggest that activated platelets may release cholesterol, which can be accumulated by cells and stored as lipid droplets.