伴刀豆球蛋白A刺激高胆固醇血症兔的单核细胞释放高水平的生长因子

复制高胆固醇血症（ｈｙｐｅｒｃｈｏｌｅｓｔｅｒｏｌｅｍｉａ，ＨＣ）兔模型，取其血液分离单核细胞（ｍｏｎｏｃｙｔｅｓ，ＭＣ），培养于含或不含伴刀豆球蛋白Ａ（ｃｏｎｃａｎａｖａｌｉｎＡ，ＣｏｎＡ）的无血清ＤＭＥ／Ｆ１２培养基中，收集不同条件的ＭＣ条件培养基（ＭＣ－ｃｏｎｄｉｔｉｏｎｅｄｍｅｄｉｕｍ，ＭＣ－ＣＭ）。并检测其促有丝分裂活性。结果表明，经ＣｏｎＡ激活的ＨＣ兔的ＭＣ－ＣＭ刺激３Ｈ－ＴｄＲ掺入ＮＩＨ３Ｔ３     

c-myc反义寡核苷酸对缺氧内皮细胞条件培养液刺激的肺血管平滑肌细胞增殖的影响

目的探讨ｃ－ｍｙｃ反义寡核苷酸（ＯＤＮｓ）对缺氧内皮细胞条件培养液（ＨＥＣＣＭ）刺激的肺血管平滑肌细胞（ＳＭＣ）增殖的影响。方法制备ＨＥＣＣＭ，用其刺激肺动脉ＳＭＣ后，Ｎｏｒｔｈｅｒｎ杂交分析ｃ－ｍｙｃ基因表达，３Ｈ－胸腺嘧啶核苷（３Ｈ－ＴｄＲ）掺入试验及细胞生长计数分析ＳＭＣ增殖情况。结果ＨＥＣＣＭ显著刺激ＳＭＣ增殖及ｃ－ｍｙｃ基因表达增强，反义ＯＤＮｓ显著下调ＨＥＣＣＭ刺激的ｃ－ｍｙｃ表达，显著抑制ＨＥＣＣＭ刺激的ＳＭＣ增殖。同义ＯＤＮｓ无上述作用。结论ＨＥＣＣＭ可能通过刺激ＳＭＣ之ｃ－ｍｙｃ表达而使ＳＭＣ增殖，反义ＯＤＮｓ通过下调ｃ－ｍｙｃｍＲＮＡ表达而抑制ＨＥＣ－ＣＭ刺激的ＳＭＣ增殖。     

急性心肌缺血综合征病人中非Q波型急性心肌梗塞的预测因素：TIMI－Ⅱ试验

急性心肌缺血综合征病人中非Ｑ波型急性心肌梗塞的预测因素：ＴＩＭＩ－Ⅱ试验分析［ＣａｎｎｏｎＣＰ，ＴｈｏｍｐｓｏｎＢ，ＭｃＣａｂｅＣＨ，ｅｔａｌ．ＡｍＪＣａｒｄｉｏｌ，１９９５，７５：９７７（英文）］在急性心肌缺血综合征中非Ｑ波型急性心肌梗塞（ＡＭＩ）...     

急性前壁心肌梗塞再灌注或非再灌注治疗后Q波消退与梗塞相关动脉开放或左室功

急性心肌缺血综合征病人中非Ｑ波型急性心肌梗塞的预测因素：ＴＩＭＩ－Ⅱ试验分析［ＣａｎｎｏｎＣＰ，ＴｈｏｍｐｓｏｎＢ，ＭｃＣａｂｅＣＨ，ｅｔａｌ．ＡｍＪＣａｒｄｉｏｌ，１９９５，７５：９７７（英文）］在急性心肌缺血综合征中非Ｑ波型急性心肌梗塞（ＡＭＩ）...     

单个核细胞趋化蛋白—1和马兜铃酸Ⅰ在诱导人类肾小管 …

目的 探讨单个核细胞趋化蛋白－１（ＭＣＰ－１）和马兜铃酸Ⅰ（ａｒｉｓｔｏｌｏｃｈｉｃ ａｃｉｄⅠ,ＡＡⅠ）及其两者的协同作用,对人类肾小管上皮细胞（ＨＫＣ）转分化的影响。方法 应用间接免疫荧光法测定ＨＫＣ细胞皮形蛋白（ｖｉｍｅｎｔｉｎ）、α－平滑肌肌动蛋白（α－ｓｍｏｏｔｈ ｍｕｓｃｌｅ ａｃｔｉｎ,α－ＳＭＡ）及角蛋白（ｃｙｔｏｃｒｅａｔｉｎ）的表达;应用流式细胞技术测定表达α－ＳＭＡ＾（＋）Ｈ     

马兜铃酸I诱导人肾小管上皮细胞转分化的作用及机制

目的：探讨马兜铃酸Ｉ（Ａｒｉｓｔｏｌｏｃｈｉｓ ａｃｉｄ Ｉ,ＡＡＩ）在人类肾小管上皮细胞（ＨＫＣ）转分化中的可能作用,了解ＡＡＩ引起肾小管间质损害的机制。方法：将体外培养ＨＫＣ细胞分为无血清对照组（Ｃ组）和ＡＡＩ实验组两组,波形蛋白和α－平滑肌肌动蛋白（α－ｓｍｏｏｔｈ ｍｕｓｃｌｅ ａｃｔｉｎ,α－ＳＭＡ）表达的变化;应用流式细胞技术检测表达α－ＳＭＡ阳性（＋）的ＨＫＣ细胞百分率;采用免疫酶标     

家兔十二指肠粘膜碳酸氢盐分泌机理的研究

本实验旨在探讨ＨＣＯ３－分泌的调节及其转运的离子通道。取大白兔近端十二指肠，置于尤氏小室间（ＵｓｓｉｎｇＣｈａｍｂｅｒ），测定血管活血肠肽（ＶＩＰ）、前列腺素Ｅ２（ＰＧＥ２），二丁酰环磷腺甙（ｄｂ－ｃＡＭＰ）及电刺激（ＥＦＳ）对碳酸氢盐（ＨＣＯ３－）分泌量、电流（Ｉｓｃ）和电位差（ＰＤ）的影响，以及缺氧、缺氯、缺钠和加入ＤＩＤＳ（４，４－ｄｉｉｓｏｔｈｉｏｃｙａｎｏｓｔｉｌｂｅｎｅ－２，２’－ｄｉｓｕｌｆｏｎｉｃａｃｉｄ）、哇巴因（Ｏｕａｂａｉｎ）和神经毒素（Ｔｅｔｒｏｄｏｔｏｘｉｎ，ＴＴｘ）后对上述指标的影响。结果示，ＶＩＰ、ＰＧＥ２、ｄｂ－ｃＡＭＰ和ＥＦＳ均刺激ＨＣＯ３－分泌和Ｉｓｃ、ＰＤ的升高，而缺氧、缺钠和哇巴因呈抑制作用。ＤＩＤＳ和缺氯则完全抑制由ＰＧＥ２引起的刺激作用，部分抑制（５０％）由ＶＩＰ的刺激作用，而对ｄｂ－ｃＡＭＰ则无抑制作用。ＴＴＸ抑制由ＥＦＳ引起的作用。ＨＣＯ３－分泌与ＶＩＰ、ＰＧＥ２及ｄｂ－ｃＡＭＰ引起的细胞内ｃＡＭＰ水平不成正相关。     

C－sis、C－myc癌基因反义寡脱氧核苷酸抑制动脉平滑肌细胞增殖

用合成Ｃ－ｓｉｓ、Ｃ－ｍｙｃ癌基因反义寡脱氧核苷酸（ＡＯＤＮ）与兔动脉平滑肌细胞（ＡＳＭＣｓ）共同培养，旨在通过ＡＯＤＮ对癌基因的封闭，动态观察ＡＯＤＮ对ＡＳＭＣｓ增殖的影响，探讨ＡＯＤＮ对动脉粥样硬化（ＡＳ）尤其是冠脉成形术后再狭窄（ＲＡＣＡ）的防治作用。结果表明：①Ｃ－ｓｉｓＡＯＤＮ、Ｃ－ｍｙｃＡＯＤＮ具有明显抑制ＡＳＭＣｓ增殖作用，其抑制作用随浓度增加而加强；②Ｃ－ｓｉｓＡＯＤＮ＋Ｃ－ｍｙｃＡＯＤＮ具有协同抑制ＡＳＭＣｓ增殖作用；③Ｃ－ｓｉｓＡＯＤＮ、Ｃ－ｍｙｃＡＯＤＮ明显抑制ＤＮＡ合成，二者联合应用，具有加强抑制ＤＮＡ合成作用。研究结果提示：Ｃ－ｓｉｓ、Ｃ－ｍｙｃ癌基因ＡＯＤＮ抑制ＡＳＭＣｓ增殖，尤其是二者联合应用，有可能为ＡＳ，特别是ＲＡＣＡ防治提供一个新的途径。     

慢性肝炎患者高压氧治疗前后肝组织中HBsAg、HBcAg检测初步探讨

目的　观察慢性肝炎（ＣＨ） 高压氧（ ＨＢＯ） 治疗前后患者的免疫功能、肝组织中ＨＢｓＡｇ 、ＨＢｃＡｇ 变化。方法：用纯氧单仓治疗（２－５ＭＰａ ,２ｈ／ｄ ,１０ｄ／ｃｙｃ ,６ｃｙｃ）３０ 例ＣＨ,治疗前后用美国ＢＥＣＭＡＮ 公司生产ＡｒｒａｙＴＭＰｒｏｔｅｉｎ Ｓｙｓｔｅｍ ３６０ 测全部患者静脉血白蛋白（ Ａ） 、γ球蛋白（γ） 、ｌｇＡ、ｌｇＧ、ｌｇＭ、和补体Ｃ３ 、Ｃ４ ;二次肝穿刺活检,ＡＢＣ 法检测肝组织中ＨＢｓＡｇ 、ＨＢｃＡｇ 。取算术均数行ｔ 检验。结果：ＨＢＯ 治疗后静脉血γ、ｌｇＧ、ｌｇＭ、明显降低,Ａ、Ｃ３ 明显升高,治疗前后差异显著（ Ｐ＜０－０５） ;肝组织中ＨＢｓＡｇ 、ＨＢｃＡｇ 变化不明显,治疗前后差异不显著（ Ｐ＞ ０－０５） 。结论：ＨＢＯ 治疗ＣＨ,可抑制患者的免疫功能,对ＨＢｓＡｇ 、ＨＢｃＡｇ 抑制作用不明显     

心肌缺血预适应对缩小心肌梗塞范围的临床研究

用培养的兔腹腔巨噬细胞条件培养基作为趋化因子的来源，用改良的Ｂｏｙｄｅｎ小室微孔滤膜法进行单核细胞趋化试验，观察了兔腹腔巨噬细胞条件培养基对单核细胞的趋化作用和抗单核细胞趋化蛋白－１（ｍｏｎｏｃｙｔｅｃｈｅｍｏａｔｔｒａｃｔａｎｔｐｒｏｔｅｉｎ－１，ＭＣＰ－１）抗体对单核细胞迁移的影响。同时用Ｎｏｒｔｈｅｒｎｂｌｏｔ分析方法检测了ＭＣＰ－１ｍＲＮＡ在该巨噬细胞的表达。结果显示，该条件培养基对单核细胞有明显的趋化作用，并被抗ＭＣＰ－１抗体所抑制。同时该巨噬细胞也能表达ＭＣＰ－１ｍＲＮＡ。这提示，巨噬细胞能分泌ＭＣＰ－１，并招引单核细胞迁入内皮下间隙，从而在动脉粥样硬化的发病过程中发挥重要的作用。     

Effect of hypercholesterolemia on vascular reactivity in the rabbit. II. Influence of treatment with dipyridamole on endothelium-dependent and endothelium-independent responses in isolated aortas of control and hypercholesterolemic rabbits

The effects of cholesterol-feeding in the presence of dipyridamole (0.60 g daily) on contractile responses and on endothelium-dependent and endothelium-independent relaxations in isolated rabbit aortas are described. The investigations were performed simultaneously with those described in Part I (Circ Res 1986; 58:552-564), where the effects of cholesterol feeding on vascular reactivity in rabbit arteries (n = 8 in each group) selected at random from the same group of animals was studied. In the hypercholesterolemic rabbits treated with dipyridamole for 8 or 16 weeks, both the increases in plasma cholesterol and the formation of fatty streaks were significantly less pronounced than in the hypercholesterolemic rabbits not receiving the drug. Segments of the isolated arteries were mounted in organ chambers for isometric tension recording. The contractions caused by acetylcholine, prostaglandin F2 alpha, norepinephrine, clonidine, and serotonin and the endothelium-independent relaxations to nitroglycerin were not significantly altered by the hypercholesterolemia in rabbits treated with dipyridamole, even after 16 weeks of treatment. Thus, the decreased responses to norepinephrine, clonidine, and nitroglycerin and the augmented responses to serotonin noted in aortas of hypercholesterolemic rabbits in Part I were absent in the dipyridamole-treated hypercholesterolemic animals. The endothelium-dependent relaxations to ATP and acetylcholine were not affected after 8 weeks of hypercholesterolemia in presence of dipyridamole, while after 16 weeks the relaxations to ATP and acetylcholine were attenuated only in the more severely affected arteries. The effects of hypercholesterolemia + dipyridamole on endothelium-dependent relaxations were significantly less pronounced than those induced by hypercholesterolemia alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regulation of concanavalin A-activated suppressor cell activity by interferon

In addition to its antiviral activity, interferon (IF) has been shown to have a wide range of immunoregulatory effects in vivo and in vitro. IF has been observed to be produced by concanavalin A (Con A)-activated suppressor cells and has also been postulated to be of importance in modulating their suppressor activity. To explore this possibility further, we examined the capacity of interferon-treated Con A-activated suppressor cells to alter the normal mitogenic response to Con A. Con A-activated suppressor cells were resistant to treatment with IF and no effect of either lymphoblastoid or leukocyte IF, when utilized in concentrations ranging from 1-1000 U/ml, could be shown on the suppressor activity of Con A-activated cells.     

Lymphocyte subpopulations, lymphoblast transformation activity, and concanavalin A-induced suppressor activity in patients with ulcerative colitis and Crohn's disease

The following immunologic in vitro tests were applied on peripheral blood mononuclear cells (PBMC) from patients with chronic inflammatory bowel disease (IBD): concanavalin A (Con A)-induced suppressor test, Con A-activated lymphoblast transformation test, and spontaneous lymphoblast transformation test. Concomitant phenotypic characterization of subsets of PBMC was performed with monoclonal antibodies. Patients with ulcerative colitis and a control group with rheumatoid arthritis showed significantly reduced activity in the Con A-activated lymphoblast transformation test compared with healthy controls and patients with Crohn's disease. The distribution of PBMC subsets and the results of the other in vitro tests were similar for patients with IBD and healthy controls. Thus the decrease in Con A-activated lymphoblast activity was not due to an increased suppressor function as measured either by functional Con A-induced suppressor test or indirectly by T8 phenotype.     

Relationship between serum cholesterol and thromboxane B2 levels and atherosclerotic lesions in rabbits fed a high cholesterol diet

The aim of our study was to evaluate the effects of diet induced hypercholesterolemia and associated atherosclerosis in rabbits on serum thromboxane B2 levels. We have determined thromboxane B2 in serum of hypercholesterolemic rabbits with atherosclerosis and in normocholesterolemic rabbits without atherosclerosis. Our data show only a mildly higher serum thromboxane levels in hypercholesterolemic rabbits and extensive atherosclerosis than in controls without atherosclerosis. In conclusion, these results show that diet induced hypercholesterolemia was not associated with thromboxane B2 generation, in spite of a diffuse experimental atheromatosis.     

精氨酸对高胆固醇血症兔冠状动脉功能的效应

目的评价左-精氨酸对高胆固醇血症兔模型冠状动脉内皮舒张功能的效应。方法雄性日本大耳白兔36只随机分为3组:对照组、高胆固醇血症组、左-精氨酸组,每组12只。两周后,处死兔,取兔冠状动脉做成动脉环。结果与对照组比较,高胆固醇血症组、左-精氨酸组兔胆固醇水平明显增高;高胆固醇血症组兔冠状动脉环在KCl预收缩基础上对内皮依赖的(乙酰胆碱累积浓度10-8～10-4mol/L)效应减弱;左-精氨酸组兔对乙酰胆碱的舒血管反应明显减低,在高浓度(乙酰胆碱10-4mol/L)下表现为冠状动脉环的收缩(P<0.05)。结论左-精氨酸不能改善高胆固醇血症兔冠状动脉的内皮舒张功能。     

Effect of high density lipoproteins on permeability of rabbit aorta to low density lipoproteins

A study was made on the effect of high density lipoproteins (HDL) on the permeability of rabbit aorta to low density lipoproteins (LDL) after intravenous administration of human HDL and human [125I]LDL to normal and hypercholesterolemic rabbits. Evaluation of radioactivity in plasma and aorta has shown that the administration of a large dose of HDL decreased the aorta permeability rate for [125I]LDL on an average by 19% in normal rabbits, and by 45% in rabbits with moderate hypercholesterolemia. A historadiographic study showed that HDL also decreased the vessel wall permeability to [125I]LDL in normal and particularly in hypercholesterolemic animals. The suggestion was made that HDL at very high molar concentration can hamper LDL transportation through the intact endothelial layer into the intima due to the ability of HDL to compete with LDL in sites of low affinity on the surface of endothelial cells.     

Experimental hypercholesterolemia induces apoptosis in the aortic valve

BACKGROUND AND AIM OF THE STUDY: Aortic valve disease is presently the number one indication for valve replacement in the United States, yet its molecular mechanisms remain unknown. As apoptosis (programmed cell death) occurs in degenerative disease states, it was postulated that experimental hypercholesterolemia is associated with apoptosis in rabbit aortic valves. METHODS: New Zealand White rabbits (n = 8) were fed a 1% cholesterol diet for 12 weeks; control rabbits (n = 8) were fed a normal diet. After sacrifice of the animals, the aortic valves were dissected. Apoptosis was identified in the valvular lesion by TdT-mediated dUTP-biotin nick end-labeling (TUNEL) technique, and confirmed with transmission electron microscopy. The number of apoptotic cells was measured by computed morphometry. RESULTS: Valves from hypercholesterolemic rabbits showed an increase in apoptosis. TUNEL staining was identified in the atherosclerotic layer of hypercholesterolemic valves (0.1% of cells), but not in the cells of controls (p <0.0001). CONCLUSION: Apoptosis is increased in rabbit aortic valves during experimental hypercholesterolemia. If fatal cellular degeneration occurs in hypercholesterolemic valve disease, these data suggest that apoptosis may play a role in the mechanism of valvular disease.     

Lack of decreased contractility in hearts from atherosclerotic rabbits

Previous studies have suggested that the contractility of isolated heart muscle removed from rabbits made hypercholesterolemic is decreased. As part of a study evaluating the effects of high-lipid diets on aortic atherosclerosis, we evaluated the contractility of perfused rabbit hearts. Six rabbits were placed on a high-lipid diet for 3 months with cholesterol levels rising to 1700 ± 400 mg %. After they were killed, their hearts were studied in an isolated, perfused, working heart apparatus at 37° C. Control animals included six rabbits matched for age, six rabbits matched for weight, and six young rabbits. Measurements were made of developed pressure, maximum dP/dt, oxygen extraction, oxygen consumption, and coronary blood flow. There were no significant differences between the contractile parameters of hearts from any group. Since previous studies were conducted with isolated heart muscle at a lower temperature, it may be that hypercholesterolemic effects on membranes may have led to the previous findings of reduced contractility. Our results suggest that hypercholesterolemia, per se, does not decrease cardiac contractility in the rabbit fed a high-lipid diet.     

Estradiol inhibits leukocyte adhesion and transendothelial migration in rabbits in vivo : possible mechanisms for gender differences in atherosclerosis.

The mechanism by which estrogens protect against atherosclerosis is not known. We evaluated in vivo whether there is a gender difference in monocyte adhesion and subendothelial migration in hypercholesterolemic rabbits and whether any gender differences observed are due to estradiol. Monocyte adhesion and subendothelial migration were assessed in a blinded fashion by analyzing a standardized segment of aorta using a scanning electron microscope. We also assessed whether estradiol modulates induction of vascular cell adhesion molecule-1 (VCAM-1) protein using Western blot and flow cytometric analyses. We observed that male rabbits develop more monocyte adhesion and subendothelial migration than do female rabbits during hypercholesterolemia. We also observed that oophorectomized rabbits given physiological estradiol supplementation demonstrate fewer adherent and subendothelial monocytes than do oophorectomized rabbits given placebo. VCAM-1 protein expression was increased in aortae obtained from hypercholesterolemic, oophorectomized animals supplemented with placebo, and this increase was attenuated by estradiol. Finally, in cultured rabbit aortic endothelial cells stimulated with lysophosphatidylcholine, we observed an increase in VCAM-1 protein that was inhibited in a concentration-dependent fashion by estradiol. We have demonstrated in vivo that there is a gender difference in monocyte adhesion to endothelial cells and transendothelial migration after hypercholesterolemia and that this gender difference is due in part to estradiol. Our results also suggest that estradiol inhibits monocyte adhesion by inhibiting expression of VCAM-1.