血栓素A2,肿瘤坏死因子和地塞米松对兔气道平滑肌细胞增？…

目的；探讨血栓素Ａ２（ＴＸＡ２）、肿瘤坏死因子（ＴＮＦ－α），地塞米松（Ｄｅｘ）对气管平滑肌细胞（ＡＳＭＣ）增生的影响。结论：ＴＸＡ２、ＴＮＦ－α在ＡＳＭＣ增生中起重要作用，Ｄｅｘ在治疗哮喘过程中，有可能加重ＡＳＭＣ的增生。     

血栓素A2、肿瘤坏死因子和地塞米松对兔气道平滑肌细胞增殖的影响

目的：探讨血栓素Ａ２（ＴＸＡ２）、肿瘤坏死因子（ＴＮＦ－α）、地塞米松（Ｄｅｘ）对气管平滑肌细胞（ＡＳＭＣ）增生的影响。方法：［３Ｈ］－ＴｄＲ掺入法及细胞计数检测上述因素作用下体外培养ＡＳＭＣ增生过程。结果：ＴＸＡ２可刺激ＡＳＭＣ增生,ＴＮＦ－α能抑制ＴＸＡ２的促增生作用,Ｄｅｘ又可使ＴＮＦ－α的抑增生作用消失。结论：ＴＸＡ２、ＴＮＦ－α在ＡＳＭＣ增生中起重要作用,Ｄｅｘ在治疗哮喘过程中,有可能加重ＡＳＭＣ的增生。     

高血压患者离体胃动脉平滑肌细胞内心钠素和内皮素的测定

采用正常血压者（ＮＴ）和高血压患者（ＥＨ）的离体动脉血管，并分离，培养动脉平滑肌细胞（ＡＳＭＣ），观察了ＡＳＭＣ合成和分泌心钠素（ＡＮＰ）内皮素（ＥＴ）的情况，探讨它们之间的相互关系及在高血压发病中的作用，结果发现：体外培养和ＡＳＭＣ能够合成和分泌ＡＮＰ，ＥＴ。ＥＭ组ＡＳＭＣ及培养液中的ＡＮＰ和ＥＴ含量显著高于ＮＴ组（Ｐ〈０．０１），ＥＴ与ＡＮＰ呈显著正相关（ｒ＝０．９２，Ｐ〈０．０１）ＥＴ与收缩     

肾上腺髓质素对内皮素促家兔气道平滑肌细胞增殖的抑制作用

在体外培养的家兔气道平滑肌细胞（ＡＳＭＣ）上，观察肾上腺髓质素（ＡＭ）对内皮素（ＥＴ）促ＡＳＭＣ增殖的影响及丝裂素活化蛋白激酶（ＭＡＰＫ）活性的变化。以探讨ＡＭ对ＡＳＭＣ增殖的调控。结果显示１０－８ｍｏｌ／ＬＥＴ－１显著刺激ＡＳＭＣ３Ｈ－ＴｄＲ参入及ＭＡＰＫ激活（Ｐ＜０．０１）。ＡＭ（１３－５２）呈剂量依赖地抑制ＥＴ－１的上述作用（Ｐ＜０．０５，Ｐ＜０．０１）。单独应用ＡＭ（１３－５２）对ＡＳＭＣ３Ｈ－ＴｄＲ参入及ＭＡＰＫ活性无明显影响。表明ＡＭ（１３－５２）可抑制ＡＳＭＣ对ＥＴ－１的增殖反应，其机理可能涉及ＭＡＰＫ活性的抑制。     

动脉粥样斑块中内皮素和一氧化氮合成酶的表达及拮抗作用

目的为探讨动脉硬化斑块的发生机制,对内皮素（ＥＴ）和一氧化氮合成酶（ＮＯＳ）的参与和拮抗作用进行研究。方法用兔主动脉硬化模型和培养的正常兔主动脉平滑肌细胞（ＳＭＣ）进行ＥＴ和ＮＯＳ的原位杂交、反转录ＰＣＲ和ＮＯＳ细胞化学检测。结果粥样斑块中ＥＴｍＲＮＡ转录增多,ＮＯＳｍＲＮＡ转录减少;与正常主动脉相比,斑块中ＥＴ基因表达增加１．２倍,而ＮＯＳ基因表达降低２２．２％;细胞化学图像分析表明,ＥＴ多肽异常增多可抑制ＳＭＣ内ＮＯＳ蛋白合成;ＥＴ－Ａ型受体拮抗剂抑制ＥＴ的作用;从而防止细胞内ＮＯＳ蛋白减少。结论ＥＴ与ＮＯＳ的平衡失调即ＥＴ异常增加和／或ＮＯＳ明显减少,与动脉粥样硬化斑块的形成有一定的关系。     

小巨核ABC法染色鉴别不典型再障与骨髓增生异常综合征的价值

小巨核ＡＢＣ法染色鉴别不典型再障与骨髓增生异常综合征的价值李玲，毛燕莉陕西省人民医院血液病研究室关键词小巨核，再生障碍性贫血，骨髓增生异常综合征再生障碍性贫血（ＡＡ）和骨髓增生异常综合征（ＭＤＳ）属干细胞疾病。ＡＡ的主要特点是骨髓增生低下，ＭＤＳ是一...     

PACAP对vSMC表达增生细胞核抗原影响的定量分析

目的：从定量角度分析垂体腺苷酸环化酶激活肽（ＰＡＣＡＰ）对血管平滑肌细胞（ｖＳＭＣ）增殖的影响。方法：以培养的猪肺动脉ＳＭＣ为实验对象，免疫组织化学ＬＳＡＢ法检测ＳＭＣ中增生细胞核杭原（ＰＣＮＡ），Ｔｉｇｅｒ９２０Ｇ细胞图象分析仪上测量计算各组细胞中ＰＣＮＡ阳性细胞的百分率；并检测阳性细胞的平均光密度（ＡＯＤ）和积分光密度（ＩＯＤ），计算阳性水平指数（ＰＬＩ）。结果：ＰＡＣＡＰ组ＳＭＣ的ＰＣＮＡ阳性率显著低于对照组细胞（Ｐ＜０．０１）；ＡＯＤ、ＩＯＤ及ＰＬＩ值也显著低于对照组（Ｐ＜００１）。结论：ＰＡＣＡＰ能抑制培养的ｖＳＭＣ增殖，可能具有抗动脉粥样硬化作用     

培养的动脉平滑肌细胞迁移的微孔滤膜检测法

培养的动脉平滑肌细胞迁移的微孔滤膜检测法同济医科大学病理学教研室（武汉４３００３０）瞿智玲，邓仲端现已公认，单核／巨噬细胞（Ｍφ）和平滑肌细胞（ＳＭＣ）在动脉粥样硬化（ＡＳ）的发生中起着重要作用，这些细胞迁入动脉内膜是ＡＳ斑块形成的关键。动脉壁内的细...     

稳定性、不稳定性心绞痛及急性心肌梗死病人冠状动脉病变的形态学差异

目的比较稳定型心绞痛（ＳＡ）、不稳定型心绞痛（ＵＡ）及急性心肌梗死（ＡＭＩ）病人冠状动脉病变的组织学差异，以阐明其发生的病理学机制。方法选取临床诊断明确的ＳＡ、ＵＡ及ＡＭＩ病人死后的尸检心脏标本，对其冠状动脉取材并做组织学及免疫组织化学观察。结果ＳＡ心脏中，其冠状动脉斑块大部分为纤维性斑块，斑块内脂质坏死中心小或无，平滑肌细胞、胶原纤维丰富而泡沫细胞少，可称为“稳定斑块”。其斑块破裂的发生率低（１４％），无继发血栓形成。ＵＡ和ＡＭＩ病例中斑块主要为“不稳定斑块”，病理特征为脂质坏死中心大（大于４０％），纤维帽薄，平滑肌细胞少而泡沫细胞多。５８例ＵＡ及２２例ＡＭＩ病人心脏中，斑块破裂的检出率分别为７６％及８２％；与ＳＡ组比较差异均具有显著性（Ｐ＜０００１），血栓检出率分别为８１％及９１％，较之ＳＡ组差异具有显著性（Ｐ＜０００１）。结论ＳＡ组“稳定斑块”多，斑块破裂少且无血栓形成，而ＵＡ和ＡＭＩ组“不稳定斑块”多，斑块破裂及血栓形成发生率高。说明斑块破裂及血栓形成为急性冠心事件的主要原因     

生长抑素抑制内皮素刺激的家兔血管平滑肌细胞增殖

为探讨生长抑素（ＳＳＴ）对内皮素（ＥＴ）刺激细胞增殖的作用其机理，本工作在培养的兔主动脉血管平滑肌细胞（ＶＳＭＣ）上发现，１０＾－８ｍｏｌ／ＬＥＴ刺激细胞增殖（＾３Ｈ＝ＴｄＲ参入增多）和丝裂素活化蛋白激酶（ＭＡＰＫ）激活，１０＾－８ｍｏｌ／ＬＳＳＴ单独作用可抑制细胞增玩具增殖但不曩ＭＡＰＫ活性。ＳＳＴ不仅呈浓度依赖性地抑制ＥＴ刺激的ＶＳＭＣ增殖（Ｐ〈０．０１），而且亦抑制ＥＴ刺激的细胞ＭＡＰＫ激     

A method to isolate morphologically distinct clones of smooth muscle cells from human saphenous vein

The monoclonal theory of atherosclerosis postulates that a certain subpopulation of vascular smooth muscle cells (VSMC) is selectively expanded in response to pathological stimuli thereby contributing to the formation of atherosclerotic plaques. VSMC cloning experiments will be important in characterizing the phenotypic composition of VSMC in atherosclerotic plaques. However, the difficulty in cloning human VSMC is well recognized. Here a technique is described that produced multiple clones from human saphenous vein. The clones could be divided into two categories based on their distinctly different morphology: (1) spindle-shaped; and, (2) epithelioid-shaped. Each clone expressed smooth muscle-a-actin and calponin, two smooth muscle-specific differentiation markers. The clonal study presented here reports for the first time that phenotypically heterogeneous smooth muscle cells coexist within human saphenous veins.     

Selective blockade of the endothelin subtype A receptor decreases early atherosclerosis in hamsters fed cholesterol.

Recent studies suggest that endothelin and its receptors may be involved in atherogenesis. To test this hypothesis, cholesterol-fed hamsters were treated with a selective endothelin subtype A (ETA) receptor antagonist BMS-182874. Characterization of hamster atherosclerotic plaques indicated that they contained a fibrous cap of smooth muscle cells, large macrophage-foam cells, and epitopes of oxidized low density lipoprotein. Messenger RNA for both ETA and ETB receptors was detected in aortic endothelial cells, in medial smooth muscle cells, and in macrophage-foam cells and smooth muscle cells of the fibro-fatty plaques. BMS-182874 inhibited the endothelin-1-induced pressor response whereas the depressor effect was unaltered, suggesting that vascular ETA receptors were selectively blocked in vivo. In hyperlipidemic hamsters, BMS-182874 decreased the area of the fatty streak by reducing the number and size of macrophage-foam cells. The results indicated that ETA receptors and thus endothelin promoted the early inflammatory phase of atherosclerosis.     

Functional analyses of coronary artery disease associated variation on chromosome 9p21 in vascular smooth muscle cells

Variation on chromosome 9p21 is associated with risk of coronary artery disease (CAD). This genomic region contains the CDKN2A and CDKN2B genes which encode the cell cycle regulators p16(INK4a), p14(ARF) and p15(INK4b) and the ANRIL gene which encodes a non-coding RNA. Vascular smooth muscle cell (VSMC) proliferation plays an important role in the pathogenesis of atherosclerosis which causes CAD. We ascertained whether 9p21 genotype had an influence on CDKN2A/CDKN2B/ANRIL expression levels in VSMCs, VSMC proliferation and VSMC content in atherosclerotic plaques. Immunohistochemical examination showed that VSMCs in atherosclerotic lesions expressed p16(INK4a), p14(ARF) and p15(INK4b). Analyses of primary cultures of VSMCs showed that the 9p21 risk genotype was associated with reduced expression of p16(INK4a), p15(INK4b) and ANRIL (P = 1.2 × 10(-5), 1.4 × 10(-2) and 3.1 × 10(-9)) and with increased VSMC proliferation (P = 1.6 × 10(-2)). Immunohistochemical analyses of atherosclerotic plaques revealed an association of the risk genotype with reduced p15(INK4b) levels in VSMCs (P = 3.7 × 10(-2)) and higher VSMC content (P = 5.6 × 10(-4)) in plaques. The results of this study indicate that the 9p21 variation has an impact on CDKN2A and CDKN2B expression in VSMCs and influences VMSC proliferation, which likely represents an important mechanism for the association between this genetic locus and susceptibility to CAD.     

Corresponding distributions of increased endothelin-B receptor expression and increased endothelin-1 expression in the aorta of apolipoprotein E-deficient mice with advanced atherosclerosis

Endothelin (ET)-1 causes proliferation of vascular smooth muscle cells (VSMC). Although it has been reported that stimulation of ET(B) receptors as well as ET(A) receptors promote proliferation of VSMC, the precise distribution of each receptor subtype in atherosclerotic vessels is unknown. Previous studies demonstrated that apolipoprotein E (apoE)-deficient mice have hypercholesterolaemia and develop severe atherosclerosis. To investigate the pathophysiological roles of vascular ET system in atherosclerosis, we examined preproET-1 messenger ribonucleic acid expression in the aorta of apoE-deficient mice, and performed immunohistochemical staining for ET-1 and each ET receptor subtype (ET(A) and ET(B) receptors) in the atherosclerotic lesions of these mice. The level of preproET-1 mRNA in the aorta was significantly higher in the apoE-deficient mice than in the control mice. Strong ET-1 staining was observed in the macrophage-foam cells, intimal and medial VSMC in the atherosclerotic lesions of the apoE-deficient mice. In addition, in the atherosclerotic lesions, strong ET(B) receptor staining was observed in the macrophage-foam cells, intimal and medial VSMC, which distribution corresponded closely to that of ET-1. ET(A) receptor staining was observed in the medial VSMC of both groups, but not in the macrophage-foam cells of the apoE-deficient mice. ET(A) receptor staining in the medial VSMC was stronger in the apoE-deficient mice than in the control mice. These results suggest that the vascular ET system, including ET-1 and ET receptors, is activated in the atherosclerotic lesions of apoE-deficient mice. Since the distribution of strong ET(B) receptor staining corresponded closely to that of ET-1, it is suggested that the ET system, mediated by ET(B) receptors, has an important role in the pathophysiology of the atherosclerotic lesions of apoE-deficient mice.     

Localization of collagen types I, III, IV and V, fibronectin and laminin in human arteries by the indirect immunofluorescence method

The distribution of types I, III, IV and V collagen and of the glycoproteins fibronectin and laminin in sections of human aortas, arteries and atherosclerotic plaques were studied using monospecific antibodies and indirect fluorescence microscopy. Types IV and V collagen and laminin were present in a narrow zone, representing the basement membrane, apposed to the endothelial layers of all these tissues. Types I and III collagen and fibronectin were located in the interstitial spaces of the intima and the media of blood vessels walls, whereas types IV and V collagen and laminin were found in the basement membranes underlying smooth muscle cells in these areas. Two types of atherosclerotic plaques were observed. Lipid-rich plaques contained less collagen and reduced amounts of the glycoproteins. Fibrous plaques consisted of regions deficient in types I and III collagen and collagen-rich regions with elevated levels of these two collagens as well as more fibronectin. The collagen-rich regions of fibrous plaques contained, however, little type IV and type V collagen and little of the glycoproteins laminin and fibronectin. This may be due to the reduced number of cells involved in the biosynthesis of these basement membrane proteins.     

Vascular smooth muscle cell proliferation in arterioles of the human endometrium

Menorrhagia affects approximately 15% of all women, often without identifiable cause. Endometrial spiral arterioles are believed to play a major role in controlling menstruation, and are a major site of menstrual loss. We postulate that alterations in the growth and development of spiral arterioles, particularly the vascular smooth muscle cells (VSMC), may contribute to menorrhagia. We examined VSMC proliferation around endometrial arterioles in control and menorrhagic tissues and the possible roles of transforming growth factor beta (TGF-beta) and endothelin in this process. Proliferating VSMC were located immuno-histochemically, then evaluated using computer-aided image analysis. VSMC proliferation was low and constant during the early stages of the menstrual cycle, increasing at the mid to late secretory stages (P < 0.002). Menorrhagic women had significantly reduced VSMC proliferation in their spiral arterioles at the mid and late secretory stages (P < 0.02). VSMC around straight arterioles proliferated at similar rates across the cycle, apart from a significant decrease in VSMC proliferation in menorrhagic women at the late secretory stage (P < 0.002). Endothelin concentrations decreased significantly in the epithelium of menorrhagic women (P = 0.05), while TGF-beta demonstrated no significant differences in the mid to late secretory tissues studied. The results indicate a significant functional difference between the spiral arterioles of control and menorrhagic women that may play a role in menorrhagia, while leaving the roles of endothelin and TGF-beta undetermined.     

Localization of fibronectin in atherosclerotic lesions by immunohistochemistry and immunoelectron microscopy]

This paper reports the results of a study on the distribution of fibronectin (FN), its form, character and source in atherosclerotic lesions, using immunohistochemistry (PAP method) and immunoelectron microscopic technique. The results showed that large amounts of FN were localized in fatty streaks, gelatinous lesions and early atherosclerotic plaques. The intima smooth muscle cells in atherosclerotic lesions synthesized more FN, and it is likely that FN represents a new marker of smooth muscle cell modulated from "contractile" to "synthetic" state. With the maturation of atherosclerotic plaque, FN did not fill the whole plaque but was concentrated only in the fibrous cap surface and basocentral part of the atheroma. We also proved that procollagen III peptide (PIIIP) distribution in atherosclerotic plaque was similar to that of FN.     

硫化氢对培养的大鼠主动脉平滑肌细胞增殖的抑制作用

目的:探讨硫化氢(H₂S)对内皮素-1(ET-1)诱导的血管平滑肌细胞(VSMC)增殖的影响及丝裂原激活的蛋白激酶(MAPK)信号转导途径的作用。方法:体外培养雄性SD大鼠主动脉VSMC, 将细胞分成对照组、血清组、内皮素组、NaHS组、血清+NaHS组和内皮素+NaHS组进行研究, 以不同浓度梯度NaHS处理VSMC, 观察对VSMC[³H]-TdR掺入和MAPK活性的影响。结果:加入5×10^-5-5×10^-4mol/LNaHS可明显浓度依赖性地抑制由内皮素诱导的VSMC增殖, 其[³H]-TdR掺入量减低, 抑制率分别为16.8%-37.4%(P＜0.01), 其MAPK活性明显减低, 抑制率为7.4%-33.6%(P＜0.05或P＜0.01)。结论:H₂S对内皮素诱导的VSMC增殖有抑制作用, 同时使MAPK活性下调。推测H₂S对VSMC增殖的抑制效应可能由MAPK信号途径所介导。