人冠状动脉硫酸乙酰肝素蛋白聚糖的分布和变化与动脉粥样硬化形成的关系

目的：观察、探讨硫酸乙酰肝素蛋白聚糖在正常及有动脉粥样硬化病变的人冠状动脉内的分布和对巨噬细胞脂质摄入的影响及其与动脉粥样硬化形成的关系。方法：应用免疫组化染色观察正常和动脉粥样硬化病变的人冠状动脉内硫酸乙酰肝素蛋白聚糖的分布;应用酶－荧光法,检测培养的巨噬细胞内胆固醇含量。结果：（１）硫酸乙酰肝素蛋白聚糖主要分布于正常冠状动脉内膜近腔面的１／３处,多定位于内皮基底膜及内膜细胞的细胞膜周围;于动脉粥样硬化病变（脂纹及斑块）内其分布密度下降,尤其是在病变深层的泡沫细胞周围分布稀少。（２）硫酸乙酰肝素蛋白聚糖能抑制巨噬细胞内脂质的聚集。结论：动脉内膜中硫酸乙酰肝素蛋白聚糖分布的减少可能与巨噬细胞易于摄入脂质转变为泡沫细胞有关,对动脉粥样硬化早期病变的形成和发展可能具有重要作用。     

人冠状动脉硫酸乙酰肝素蛋白聚糖的分布和变化与动脉粥样硬化形成 …

目的：观察、探讨硫酸乙酰肝素蛋白聚糖在正常及有动脉粥样硬化病变的人冠状动脉内的颁２和对巨噬细胞脂质摄入的影响及其与动脉粥样硬化形成的关系。方法;应用免疫组化染色观察正常和动脉粥样硬化病变的人冠状动脉内硫酸乙酰肝素蛋白聚糖的分布;应用酶－荧光法,检测培养的巨噬细胞内胆固醇含量。结果：（１）硫酸乙酰肝素蛋白聚糖主要分布于正常冠状动脉内膜近腔面的１／３处,多定位于内皮基底膜及内膜细胞的细胞膜周围;于动脉     

蛛网膜下隙出血后脑动脉痉挛形态学研究

采用大鼠蛛网膜下隙出血模型，经光镜和Ｖｉｄａｓ图像分析的方法，对不同时间段的脑动脉平滑肌的横断面积（Ｓ１），内膜的横断面积（Ｓ２），脑动脉壁横断面积（Ｓ３），脑动脉腔横断面积（Ｓ４），Ｖ１，平滑肌的体密度（Ｓ１／Ｓ３）；Ｖ２；内的体密度（Ｓ２／Ｓ３）；Ｄ１；蛛网膜下隙面脑动脉壁厚度；Ｄ２：脑面及动脉壁厚度进行了观察测定发现蛛网膜下隙出血后脑血管痉挛具有双相性，管腔缩窄，管壁增厚，急性脑血管痉挛比迟     

皮下埋植避孕法对子宫内膜影响的临床病理研究

目的：观察皮埋ＬＮＧ对ＳＤ鼠子宫内膜形态结构变化的影响，探讨术后突破性出血（ＢＴＢ）的机制。方法：用显微镜观察１５只ＳＤ鼠，分空白对照组、埋植ＬＮＧ组和假手术对照组，于实验后３０天取ＳＤ鼠子宫内膜行光镜观察。结果：埋植ＬＮＧ后ＳＤ鼠子宫内膜颗粒细胞（ＥＧＳ）明显增多，网状纤维稀疏断裂、溶解，微血管总面积、微血管面积百分比、微血管密度均增加。结论：皮下埋植ＬＮＧ使ＳＤ鼠子宫内膜颗粒细胞增多，网状纤维溶解，微血管变化而致术后ＢＴＢ。     

SHR血浆NPY、主动脉平滑肌细胞NPY受体的变化及药物的干预作用

目的：观察自发性高血压大鼠（ＳＨＲ）血浆神经肽Ｙ（ＮＰＹ）、血管平滑肌细胞（ＶＳＭＣ）ＮＰＹ受体的变化及美托洛尔、培哚普利干预的影响。方法：用放射免疫分析法和受体放射配体结合分析法测定血浆ＮＰＹ及ＶＳＭＣ上ＮＰＹ受体密度的变化。结果：ＳＨＲ血浆ＮＰＹ含量明显高于ＷＫＹ，血压的高低与血浆ＮＰＹ的量呈明显的正相关。培哚普利降压的同时亦降低ＳＨＲ血浆ＮＰＹ的量，而美托洛尔对ＮＰＹ量则无影响；培哚普利引起     

硫酸软骨素蛋白聚糖与年轻人冠状动脉粥样硬化的关系

硫酸软骨素蛋白聚糖与年轻人冠状动脉粥样硬化的关系杨方，赵培真，张英珊，韩晓男，杨瑞彪，梁凤玲，武阳丰，赵红，张振声动脉壁蛋白聚糖（ＰＧ）主要由平滑肌细胞（ＳＭＣ）和内皮细胞（ＥＣ）合成、分泌，为细胞外基质（ＥＣＭ）的重要成分之一，ＰＧ在维持血管壁的完...     

大鼠保留交感神经的高选择性迷走神经切断术实验模型的建立

目的：建立保留交感神经的高选择性迷走神经切断术（ＨＳＶ－ＡＰ）的动物实验模型。方法：６０只雄性ＳＤ大鼠随机分为三组：ＨＳＶ－ＡＰ组、ＨＳＶ组和正常对照组（Ｃ组），每组２０只。结果：ＨＳＶ－ＡＰ术后胃壁泌酸区交感神经分布密度与Ｃ组比较，下降不显著，去甲肾上腺素含量与Ｃ组无差别（７４５．０±４０８．９ＶＳ８９９．６±２３５．１，Ｐ＞０．０５）。而ＨＳＶ术后胃部泌酸区交感神经分布密度显著下降，去甲肾上腺素含量低于ＨＳＶ－ＡＰ术后（２９３．０±２１４．８ＶＳ７４５．８±４０８．９，Ｐ＜０．０１）。ＨＳＶ－ＡＰ术后胃体部迷走神经追踪脑干内未见标记细胞，而胃窦部迷走神经追踪脑干内可见标记细胞。结论：本试验证实采用保留胃小弯血管的ＨＳＶ—ＨＳＶ－ＡＰ术式，既可完整切断支配胃部泌酸区的迷走神经，又可保留交感神经。     

子宫内膜组织ER、PR及PCNA表达与子宫内膜增生过长的关系

目的：探讨子宫内膜增生过长的发病机理，为临床内分泌治疗提供理论基础。方法：应用免疫组织化学Ｓ－Ｐ法，对手术切除和诊刮的６７例不同时期子宫内膜和不同类型增生过长子宫内膜标本进行ＥＲ、ＰＲ和ＰＣＮＡ含量检测分析。结果：ＥＲ、ＰＲ在正常增生期子宫内膜中的含量显著高于分泌期（Ｐ＜０．０１），在单纯性增生过长和复杂性增生过长子宫内膜中ＥＲ、ＰＲ的含量也有显著差异（Ｐ＜０．０１）。各组增生过长子宫内膜中ＥＲ的含量高于ＰＲ（Ｐ＜０．０１）。ＰＣＮＡ在内膜分泌期和伴有非典型增生的子宫内膜中含量高（Ｐ＜０．０１）。结论：ＥＲ主要与子宫内膜增生过长有关，ＰＣＮＡ在非典型增生子宫内膜中过表达可能与宫内膜异常生长有关。     

核心蛋白聚糖对TGF阻诱导的人肾小管上皮细胞产生胶原的影响

目的：探讨核心蛋白聚糖对转化生长因子β1（TGFβ1）诱导的人近端肾小管上皮细胞（HK-2）I、Ⅲ型胶原表达的影响。方法：将体外培养的HK-2细胞分为：（1）阴性对照组；（2）10μg／L TGFβ1组；（3）TGFβ1（10μg/L）＋（10μg/L）核心蛋白聚糖组；（4）TGFβ1（10μg／L）＋（100μg/L）核心蛋白聚糖组。倒置显微镜下观察加入刺激因子48h后肾小管上皮细胞的细胞形态学改变；应用逆转录-聚合酶链反应（RT-PCR）观察不同浓度的核心蛋白聚糖对HK-2细胞I、Ⅲ型胶原表达变化的影响。结果：加入刺激因子48h后，（1）组细胞形态与正常HK-2细胞形态基本一致，大部分仍为椭圆形；（2）组细胞形态发生明显的变化，大部分细胞由椭圆形拉长为长梭形；（3）和（4）组，梭形样细胞明显减少，尤其是（4）组梭形样细胞减少更为明显。（2）组HK-2细胞I型胶原mRNA表达上升到（1）组的27.86倍，Ⅲ型胶原mRNA的表达上升到（1）组的21.83倍。（3）和（4）组与（2）组相比，I型胶原mRNA的表达分别下降了36.39％、53.36％，Ⅲ型胶原mRNA的表达分别下降了26.35％、47.96％（P〈0.05），但仍未下降到正常水平。结论：核心蛋白聚糖能抑制TGFβ1诱导的人近端肾小管上皮细胞I、Ⅲ型胶原的表达，可能是核心蛋白聚糖抑制肾间质纤维化的原因之一。     

p27Kip1蛋白在子宫内膜癌中的表达及其意义

目的：探讨子宫内膜癌中ｐ２７＾Ｋｉｐ１蛋白的表达情况及临床病理意义。方法：采用免疫组化Ｓ－Ｐ法检测１０５例子宫内膜癌ｐ２７＾Ｋｉｐ１蛋白的表达,并运用流式细胞术检测４６例子宫内膜癌组织的ＤＮＡ含量。结果：子宫内膜癌ｐ２７＾Ｋｉｐ１蛋白阳性表达率为６９％（７２／１０５例）,明显低于正常增生期子宫内膜及单纯增生、复合增生子宫内膜总的阳性率（９１％,Ｐ〈０．０１）,而与不典型增生子宫内膜的ｐ２７＾Ｋｉｐ     

Apoptosis participates in cellularity regulation during rat aortic intimal thickening.

Intimal thickening induced after endothelial denudation of rat aorta is though to be due to migration and proliferation of smooth muscle cells (SMC). When the reendothelialization is achieved, intimal thickening shows an important decrease in cellularity. Using in situ end labeling of fragmented DNA and electron microscopy, we show that this remodeling is accompanied by apoptosis of SMC. The number of apoptotic SMC becomes important 15 days after endothelial injury and reaches a maximum at 20 days; at 45 days the intimal thickening is reendothelialized and no more apoptotic SMC are detected. Apoptotic SMC show nuclear and cytoplasmic condensation as well as cytoplasmic vacuolization. Our results indicate that apoptosis is an important mechanism in the regulation of intimal thickening evolution.     

Effect of renal and genetic hypertension and endotoxin injections on cultivated smooth muscle cells derived from different regions of the aorta

The proliferation capacity of cultured smooth muscle cells (SMC) from standardized explants of different aortic layers or regions was investigated. SMC outgrowth from explants was compared in renal and genetic hypertensive rats and in renal hypertensive and staphylolysine injected minipigs. SMC proliferation in the minipigs was always greater in the upper thoracic aorta than in the lower thoracic aorta. In the latter, the intima was more reactive than either of the medial layers. A significant increase in proliferation was observed in hypertensive minipigs in the intimal and inner medial layer of the upper and in the outer medial layer of the lower thoracic aorta. Staphylolysine injections led to a significant increase in proliferation of the intimal and outer medial layer of the upper thoracic aorta. Renal and genetic hypertensive rats showed significantly higher levels of SMC proliferation in the aortic arch and the upper thoracic aorta. In the lower thoracic aorta, only explants from genetic hypertensive rats showed significantly greater outgrowth. These data show that pathological SMC proliferation is dependent on the kind of stimulus as well as on the anatomical position of the SMC in the aortic wall.     

Age and fibroplasia as preconditions for atheronecrosis in the human thoracic aorta

The atheronecrotic core of an aortic plaque is an easily recognized structural feature when present in histologic sections. This feature tends to be associated with other characteristics of the aorta, chief among these being old age, marked intimal fibroplasia, and diminished numbers of intimal smooth-muscle cells. The statistical relationships among these aortic characteristics were examined in a series of 356 autopsies. Intimal fibroplasia tended to be directly proportional to age. The density of smooth-muscle cells tended to be inversely proportional to intimal fibroplasia. The total cellularity of the intima was almost constant without regard to age or intimal thickness. The probability of finding atheronecrosis in a randomly chosen sample from the lateral thoracic aorta was directly proportional to age and to intimal thickness after appropriate mathematical transformations. Against this background of what is usual, two atypical kinds of lesion were identified.     

Antibody ligation of human leukocyte antigen class I molecules stimulates migration and proliferation of smooth muscle cells in a focal adhesion kinase-dependent manner

Chronic rejection manifests as transplant vasculopathy, which is characterized by intimal thickening of the vessels of the allograft. Intimal thickening is thought to result from the migration and proliferation of vascular smooth muscle cells (SMC) in the vessel media, followed by deposition of extracellular matrix proteins. The development of post-transplantation anti-human leukocyte antigen (HLA) antibodies (Ab) is strongly correlated with the development of transplant vasculopathy and graft loss. Here we demonstrate that cross-linking of HLA class I molecules on the surface of human SMC with anti-HLA class I Ab induced cell proliferation and migration. Class I ligation also increased phosphorylation of focal adhesion kinase (FAK), Akt, and ERK1/2 in SMC. Knockdown of FAK by siRNA attenuated class I-induced phosphorylation of Akt and ERK1/2, as well as cell proliferation and migration. These results indicate that ligation of HLA class I molecules induces SMC migration and proliferation in a FAK-dependent manner, which may be important in promoting transplant vasculopathy.     

Enhanced Intimal Proliferation upon Injury to Pre-Existing Neointima and Resistance of Neointimal Cells to Cell Death

Recent evidence supports a role for cell death and inflammation as etiologic factors in neointimal formation and restenosis after angioplasty. This study was undertaken to examine the pattern and intensity of the proliferative response, cell death, and activation of inflammatory, endothelial and smooth muscle cells (SMC) in a model of intimal reinjury. Two ballooning injuries were performed to rat aorta, the second one 14 days after the first injury. Our results demonstrate that ballooning injury to pre-existing neointima differs clearly from an injury to a normal aorta. First, ballooning injury to pre-existing neointima doubled the proliferative response of SMC and intimal thickening, but proliferation of SMC occurred only in the intima, and did not extend into the media. Second, within four hours after the first injury, the number of TUNEL-positive SMC in the media increased from 3% to 23%, but no such increase was found in the pre-existing neointima after the second injury. Third, the prompt proliferative response of intimal SMC after the second injury was linked with a significant increase in endothelial P-selectin and neointimal VCAM-1 immunoreactivity, compared to the first injury at corresponding time points, followed by high numbers of activated ED3+ macrophages and CD4+ T cells in the developing neointima. A balance in injury-induced cell death and proliferation obviously maintains stable cell numbers observed in the media, whereas in the neointima, the resistance of SMC to injury-induced cell death may contribute to a rapid lesion formation in restenosis.     

c-jun反义核酸对自体移植静脉内膜增生和ET-1水平的影响

目的 :观察反义c - jun核酸对自体移植静脉内膜增生及血管活性因子内皮素 - 1(ET - 1)的影响。方法 :选择 6 0只SD大鼠 ,等分为实验组和对照组 ,均行自体颈外静脉、腹主动脉移植手术 ,实验组移植静脉周围和血管吻合口周围应用反义c- jun核酸凝胶涂布 ;对照组仅行凝胶涂布。于手术时取静脉血 1ml,放射免疫分析检测血浆ET - 1的水平。术后 2周取出移植血管 ,分别行病理学、免疫组织化学检测移植血管内膜厚度 ,内膜平滑肌细胞数及增殖细胞核抗原和脱氧核糖核酸反映血管平滑肌细胞增殖情况的指标的表达情况。同时在另一侧颈外静脉取静脉血 1ml,仍采用放射免疫分析检测血浆ET - 1水平。结果 :移植静脉术后动脉化 ,管壁增存 ,血浆ET - 1水平升高 ,但转染c - jun反义核酸组移植血管内膜厚度及VSMC增殖均较对照组减少 ,PCNA和DNA阳性表达情况亦较对照组明显减少 ,血浆ET - 1水平升高幅度低于对照组。结论 :反义c - jun核酸可抑制VSMC分裂而减少VSMC的增殖 ,降低促进血管收缩和细胞增殖的ET - 1的表达 ,从而有效地抑制移植静脉内膜的过度增生。     

Rabbit ductus arteriosus during development: Anatomical structure and smooth muscle cell composition

The anatomical structure as well as the smooth muscle cell (SMC¹) composition of the ductus arteriosus (DA) were studied in rabbits ranging in age from 29 days of gestation to 20 days after birth. Computerassisted, three-dimensional reconstructions of hematoxylin-eosin stained serial cryosections from ductus arteriosus-aorta (DA-AO) junctures revealed that DA in animals near term is separated from the aorta by a “septumlike” structure that is continuous with the aortic wall. Two days after birth, obliteration of DA is almost complete, and a small “pocketlike” cavity appears in the pre-existing site in which DA merged into the aorta. This small cavity in the aortic arch was still evident in the large majority of animals examined even 20 days after birth, as also demonstrated by scanning electron microscopy. At this time period DA consisted of a central, fibrotic region surrounded by several layers of SMC (the ligamentum arteriosum, LA) and ended within the aortic media just above the small cavity, forming a round “scar.” Vascular SMC composition of DA during closure was examined by means of indirect and double immunofluorescence procedures, using a panel of monoclonal antibodies against some cytoskeletal and cytocontractile proteins (vimentin, desmin, smooth muscle (SM), and nonmuscle (NM) myosinisoforms). “Intimal cushions” were particularly evident from 5 hr after birth and were found to be desmin-negative, homogenously reactive for vimentin and NM myosin, and heterogeneously stained with anti-SM myosin antibody. In SMC subjacent to the “intimal cushions,” distribution of vimentin and SM myosin was homogeneous, whereas the one of desmin and NM myosin content was heterogeneous. The cytoskeletal and cytocontractile protein content displayed by SMC during the closure of DA is similar to that of “intimal thickening” found in some pathological conditions of the arterial wall in adult rabbits. Completation of DA closure (day 2) was accompanied by the disappearance of cellular heterogeneity in myosin isoform distribution in both the “intimal cushions” and the underlying media. These results give new insights into: (1) the structure of DA-AO juncture, which can be relevant to the physiology of blood circulation in the fetus, and (2) the phenotypic similarity of vascular SMC populations involved in the formation of “intimal cushions” and “intimal thickening”.     

Factors controlling smooth-muscle cell proliferation.

Injury to the arterial wall normally elicits a rapid and significant increase in smooth-muscle cell (SMC) replication with the subsequent development of intimal lesions. A variety of factors have been proposed to control SMC replication, but recent work has highlighted the role of basic fibroblast growth factor (bFGF) and platelet-derived growth factor in this process. In the carotid artery of the uninjured rat, we have shown that the SMCs express mRNA for bFGF and that bFGF can be readily extracted from these arteries. Following mechanical injury to the artery, ie, after balloon injury, we suggested that bFGF is released from damaged cells and then stimulates adjacent SMCs. In support of this concept, the infusion of a blocking antibody to bFGF was found to significantly inhibit the early SMC replication induced by use of a balloon catheter. The addition of the antibody at the time of injury, however, did not inhibit the development of intimal lesions. In contrast, studies by us and other investigators have shown that platelet-derived growth factor is not directly important for SMC replication after balloon injury, but that it plays a key role in stimulating the migration of SMCs into the intima. Intimal SMC replication was not inhibited with antibodies to either bFGF or platelet-derived growth factor. Therefore, while significant inroads have been made in understanding the initial events, we still do not fully understand all the processes involved in the proliferation of arterial intimal lesions.     

Effect of aging on aortic morphology in populations with high and low prevalence of hypertension and atherosclerosis. Comparison between occidental and Chinese communities.

A comparative morphologic study of aortic changes with aging was conducted in different populations in an attempt to separate the effects of hypertension and atherosclerosis. Chinese and the occidental populations were chosen, as they are known to have a high prevalence of hypertension and atherosclerosis, respectively. Aortic tissue was collected from occidental (American and Australian) and Chinese populations from three geographic locations. Postmortem specimens were obtained from four fixed locations: ascending aorta (A), descending thoracic aorta (B), and abdominal aorta (suprarenal [C] and above the aortic bifurcation [D]). Histologic sections were used to measure aortic circumference, medial thickness, intimal thickness, and grade of atherosclerosis. Kidney sections were used to confirm the presence or absence of hypertension. A total of 302 cases (age range, 19 to 104 years; Male-to-female ration, 2:1) were studied: 112 Americans, 80 Australians, and 110 Chinese. Cases were divided into three age groups: 19 to 44; 45 to 64; and 65 years and older. The aortic circumference progressively decreased from sites A to D in all populations and age groups. The aortic circumference increased with age, and the increase was independent of the aortic location. When the populations were separated, however, the greater increase was at location A in the Chinese (P = .008) and locations D in the occidental (P = .13), a population contrast that was significant only in location A. Intimal thickness increased with advancing age and was maximal in the abdominal aorta. The population differences also were significant for intimal thickness and were significantly greater in the occidental population in B, C, and D locations, whereas for atherosclerosis significance was only seen in location D. Hypertension (as defined by the morphologic changes in the kidney) after adjusting for age, height, and weight resulted in no statistical significant effect on aortic circumference or on intimal thickness, but did show a significant increase in atherosclerosis score at locations B, C, and D. Also after adjusting for age, height, and weight, the Chinese had a significantly larger aortic circumference in location A compared with the occidental population, whereas in location D the occidentals with hypertension had a significantly larger circumference compared with Chinese, probably due to an interaction of atherosclerosis and hypertension. After similar adjustments, the medial thickness in locations A and C, the intimal thickness in B, C, and D, and atherosclerosis score in D were significantly greater in occidental than Chinese populations.(ABSTRACT TRUNCATED AT 400 WORDS)     

Expression of thrombomodulin in human aortic smooth muscle cells with special reference to atherosclerotic lesion types and age differences

Expression of thrombomodulin (TM) in atherosclerotic lesions of the human aorta (8 cases of diffuse intimal thickening, 4 fatty streaks, 11 atheromatous plaques, and 5 fibrous plaques) as well as in undiseased aortas of 5 infants obtained at autopsy was studied immunohistochemically using a novel polyclonal antibody against human TM. TM was expressed in intimal smooth muscle cells (SMC) besides endothelial cells and foamy macrophages in almost all patients (26/28). In addition, medial SMC in adult cases over 27 years of age expressed TM. In young adults with diffuse intimal thickening under 26 years of age, medial SMC showed no TM expression whereas intimal SMC did show it. Both intimal and medial SMC in infants showed no TM expression. An immunofluorescence method showed TM expression in cultured adult human SMC. These findings indicate that TM expression in SMC may depend on patient age as well as lesion type of atherosclerosis.