冠状动脉粥样硬化斑块稳定性与血清基质金属蛋白酶-9及超敏C反应蛋白浓度的关系

目的探讨冠状动脉粥样硬化(atherosclerosis,AS)斑块稳定性与血清基质金属蛋白酶-9(matrix metallo-proteinase-9,MMP-9)及超敏C反应蛋白(high sensitivity C-reactive protein,hs-CRP)浓度的关系。方法按照随机分组方法将56只大白兔划分为2组:A组为AS研究组40只,A组分为A1亚组(斑块破裂组)、A2亚组(斑块未破裂组);B组为参照组16只。A组采用(标准颗粒+1%胆固醇)进行喂养+球囊损伤,B组采用标准颗粒喂养。在研究期间,动态监测A、B两组血清MMP-9和hs-CRP浓度及血脂的变化情况。结果研究期间,B组兔的体质量与A1、A2亚组比较,差异有统计学意义(P0.05)。实验开始、实验第14周末,B组血脂指标变化不明显,A2和A1亚组的血脂指标由实验开始时到实验第14周末呈上升趋势;实验第14周末,B组与A1、A2亚组的血脂浓度比较,差异均有统计学意义(P0.01);但是A2亚组和A1亚组血脂浓度比较,差异无统计学意义(P0.05)。在第4周时,B组与A1亚组、A2亚组的血清MMP-9和hs-CRP浓度比较,差异有统计学意义(P0.01)。在第10周时,B组、A2亚组和A1亚组的血清MMP-9和hs-CRP浓度比较,差异有统计学意义(P0.01);A1亚组血清MMP-9和hs-CRP浓度高于A2亚组,且差异有统计学意义(P0.01)。在第14周时,A1亚组和A2亚组的血清MMP-9和hs-CRP浓度均高于B组,差异有统计学意义(P0.01);A1亚组血清MMP-9和hs-CRP浓度高于A2亚组,且差异有统计学意义(P0.01)。实验过程中A1、A2两亚组的血清MMP-9、hs-CRP浓度均呈现升高趋势(P0.01)。实验兔血清MMP-9浓度和hs-CRP浓度之间为正相关关系(r=0.967,P=0.001)。结论 MMP-9和hs-CRP呈正相关关系,且两者的浓度与AS斑块稳定性密切相关,斑块越不稳定,MMP-9和hs-CRP的浓度越高。     

罗格列酮对动脉粥样硬化兔主动脉NF-κB蛋白质表达的影响

目的 探讨罗格列酮对动脉粥样硬化兔核因子(NF)-κB的影响. 方法 大耳白兔37只随机分为空白对照组、动脉粥样硬化(AS)组、罗格列酮治疗组,14 w后检测血脂谱、NF-κB及主动脉斑块面积.结果 罗格列酮治疗组较AS组主动脉斑块面积、NF-κB水平明显降低(P＜0.01),HDL-C水平显著升高(P＜0.01).结论 罗格列酮可以改善血脂异常,减小主动脉斑块面积,降低NF-κB表达,抑制慢性炎症反应,对AS有一定抑制作用.     

桑葚提取物对实验性兔动脉粥样硬化形成过程中细胞间黏附分子-1表达的影响

目的 探讨细胞间黏附分子(ICAM-1)在动脉粥样硬化(AS)形成中的作用及桑葚提取物的影响.方法 新西兰纯种白兔30只,随机分为对照组6只(喂饲全谷物饲料) 和模型组6只(予高脂饮食喂养) ;桑葚组18只,分为低、中、高剂量组,分别给予1、5、10 g/kg桑葚提取液灌胃,1次/d.各组喂养8 w,于0 w、2 w、4 w、6 w、8 w末采血,测血浆胆固醇、甘油三酯、低密度脂蛋白、高密度脂蛋白的水平.于8 w末采完血后处死兔,取胸主动脉和冠状动脉用免疫组化法检测胸主动脉、冠状动脉ICAM-1表达.结果 对照组血脂在实验前后无明显变化,而模型组血浆胆固醇、甘油三酯、低密度脂蛋白在2 w末时较实验前及对照组即已明显升高(P<0.01).免疫组化染色显示,对照组兔胸主动脉壁、冠状动脉壁ICAM-1呈阴性表达,而模型组ICAM-1内皮细胞表达显著增强,且斑块内和中膜平滑肌表达亦增强、表达范围较大.桑葚提取物三组动脉壁ICAM-1表达显示,桑葚低、中剂量组的表达有所减弱,而桑葚高剂量组呈明显的弱阳性表达.结论 ICAM-1参与了AS的形成和发展,桑葚提取物可抑制ICAM-1的表达,从而抑制AS的形成.同时高脂血症与ICAM-1的表达间可能为一种剂量正相关关系.     

阿托伐他汀对颈动脉粥样硬化斑块患者血浆高敏C反应蛋白的影响

目的观察应用阿托伐他汀干预后颈动脉粥样硬化患者颈动脉粥样硬化斑块及血浆高敏C反应蛋白(hs-CRP)的变化。探讨他汀类药物预防缺血性脑血管病的机制。方法收集2006年7月—2008年10月福建省立医院门诊及住院的有颈动脉粥样硬化患者80例,随机分为阿托伐他汀药物干预组(A组,40例)及非他汀药物干预组(B组,40例)。并设无颈动脉粥样硬化对照组(C组,40例)。A组在饮食控制的基础上给予阿托伐他汀20mg口服,1次/日,疗程16周。B组采用饮食控制,加强体育运动,减轻体重等方法。干预8周后,观察血脂及血浆hs-CRP的变化,8周、16周后复查颈动脉多普勒超声,并进行统计分析。结果干预前A组与B组两组间血浆血脂、hs-CRP水平无明显差异。两组血浆、血脂、hs-CRP水平均高于对照组(P0.05)。干预8周后A组血浆血脂、hs-CRP水平明显低于B组(P0.05)。干预8周时两组患者颈动脉粥样硬化斑块无明显改变,16周后药物干预组颈动脉粥样硬化斑块明显变小,易损斑块减少。结论他汀类药物在治疗颈动脉粥样斑块中不仅有降脂的作用,还有降低血浆hs-CRP起到抗炎稳定斑块的作用,从而起到预防缺血性脑血管病的作用。     

基质金属蛋白酶-9对大鼠动脉粥样硬化斑块内血管生成及斑块稳定性的影响

目的:研究基质金属蛋白酶-9（MMP-9）与动脉粥样硬化(AS)斑块内血管生成的关系及强力霉素干预的效果。方法: 将36只雄性Wistar大鼠随机分为对照组（A组，普通饮食喂养）、AS组（B组）和强力霉素干预组（C组），B组和C组均给予高脂饮食＋维生素D3腹腔注射，C组同时给予强力霉素腹腔注射。采用酶法并以全自动生化分析仪测量血脂，双抗体夹心ABC-ELISA法检测血清MMP-9的水平。取主动脉切片行HE染色，观察斑块形态，计数易损斑块的数目。对内皮细胞标记物CD34行免疫组织化学染色法以检测斑块内新生血管密度。结果: B组和C组各项血脂的水平无明显差异，但均明显高于A组（P<0.05）。B组和C组血清MMP-9的水平明显高于A组（P<0.05），B组又高于C组（P<0.05）。与B组比较，C组易损斑块数、CD34+面积/扫描面积(R)比均降低(P<0.01)。结论: 强力霉素能增强斑块稳定性，这种作用可能是通过降低MMP-9的水平进而减少了斑块内血管生成。     

睾酮对雄兔氧化炎性系统和动脉粥样硬化斑块稳定性的影响

目的:探讨睾酮对雄兔血丙二醛(MDA)、超氧化物歧化酶(SOD)、高敏C反应蛋白(hs-CRP)、基质金属蛋白酶-9(MMP-9)、血红素氧化酶-1(HO-1)和动脉粥样硬化斑块稳定性的影响。方法:将66只雄性新西兰纯种兔随机分为4组,其中正常对照组10只(A组),喂以普通饲料;假去势+球囊损伤颈动脉组16只(B组),去势+球囊损伤颈动脉+生理剂量睾酮(6 mg/kg/2周)肌注组16只(C组)、去势+球囊损伤颈动脉+生理盐水肌注组24只(D组)均喂以高脂饲料。在实验第8周随机抽取处死部分动物,观察颈动脉病变的形态特征,抽血测睾酮、MDA、SOD、hs-CRP、MMP-9及HO-1水平。结果:D组兔血睾酮水平显著降低;B,C组较D组兔血MDA、hs-CRP及MMP-9水平显著降低,SOD、HO-1水平显著升高;且B,C组较D组兔动脉粥样斑块的面积和内-中膜厚度(IMT)显著减小,斑块纤维帽增厚、胶原含量明显增加。结论:生理剂量睾酮可以影响雄兔血MDA、SOD、hs-CRP、MMP-9及HO-1水平,并能调节动脉粥样硬化斑块进展与斑块的稳定性。     

CyPA与CD147在兔动脉粥样硬化易损斑块中的表达

目的探讨亲环素A(Cy PA)/CD147在兔动脉粥样硬化易损斑块中的表达。方法新西兰雄性白兔16只,3月龄,随机分为对照组和模型组,每组8只。利用液氮损伤内膜+高脂饮食的方法建立易损斑块模型,对照组正常饮食,不做任何处理,0周和13周分别检测兔血清C反应蛋白(CRP)、Cy PA和CD147表达水平。术后13周处死动物,取血管行HE染色、Masson染色,观察血管形态,并做巨噬细胞、Cy PA、CD147免疫组织化学染色。结果对照组未见斑块形成,模型组兔颈动脉形成典型的易损斑块,斑块内Cy PA和CD147表达丰富,呈带状分布特征,两者在同一斑块中具有共区域性;13周时模型组兔血CRP、Cy PA和CD147水平较0周及同时期对照组均明显升高(P0.05)。结论易损斑块中Cy PA、CD147表达丰富,Cy PA和CD147是易损斑块的危险因素,其表达与易损斑块的存在呈正相关。     

化瘀通脉方对动脉粥样硬化模型兔一氧化氮、内皮素-1表达的影响

目的观察化瘀通脉方对动脉粥样硬化(AS)模型兔一氧化氮(NO)、内皮素(EP)-1表达的影响。方法取雄性健康新西兰大耳白兔40只,随机分为空白组、模型组、对照组、治疗组,每组10只。采用免疫损伤加高脂饲料喂养方法建立新西兰大耳兔AS模型。测定血清NO、血浆ET-1水平。结果实验8 w末,AS兔血清ET-1显著升高,而NO显著降低(P0.05,P0.01)。实验16 w末,治疗组血清ET-1水平较模型组显著降低,NO较模型组显著升高(P0.05,P0.01)。结论化瘀通脉方具有较好的抗AS作用,这可能与其能有效地调节NO/ET-1平衡有关。     

脑心通胶囊和辛伐他汀稳定易损斑块的对比研究

目的观察脑心通胶囊和辛伐他汀对易损斑块的稳定作用。方法32只兔给予球囊损伤腹主动脉加高脂饲料喂养,12周末30只造模兔随机分为自然消退组、脑心通组和辛伐他汀组,每组10只。24周末在腹主动脉斑块处转染携带人野生型P53基因,26周末给予中国斑点蝰蛇毒（CRVV）和组胺触发斑块破裂。于26周末测定血脂、血浆纤维蛋白原、高敏C反应蛋白（hs-CRP）和基质金属蛋白酶1（MMP-1）水平,并进行血管内超声检测。结果治疗后脑心通组和辛伐他汀组的总胆固醇、低密度脂蛋白、hs-CRP及MMP-1显著低于自然消退组（P〈0.05和P〈0.01）。与辛伐他汀组比较,脑心通组能显著降低血浆纤维蛋白原浓度（P〈0.05）。脑心通组和辛伐他汀组血管外弹力膜面积（EEMA）、斑块面积（PA）和管腔面积狭窄（LAS）百分率较之自然消退组显著降低（P〈0.05或P〈0.01）。结论脑心通胶囊和辛伐他汀能通过降低血脂、hs-CRP和MMP-1水平等机制稳定易损斑块。     

骨髓间充质干细胞移植修复动脉粥样硬化破裂斑块的研究

目的研究骨髓间充质干细胞(MSC)移植对动脉粥样硬化破裂斑块的修复作用。方法选择24只雄性新西兰白兔,采用自创液氮冻伤术,随机各取2只兔制备动脉粥样硬化斑块形成及斑块破裂模型,将剩余兔再随机分为移植组10只,对照组10只。ELISA法检测治疗前后血清基质金属蛋白酶9(MMP-9)、高敏C反应蛋白(hs-CRP)及纤溶酶原激活物抑制剂1(PAI-1)的变化。HE染色和Masson三色染色,光镜观察斑块修复情况;免疫组织化学法检测5-溴脱氧尿核苷标记的阳性细胞。结果 MSC移植4周后,移植组新生内皮细胞及胶原纤维明显增多;移植组斑块区5-溴脱氧尿核苷标记的阳性细胞明显增多;MSC移植4周后,与对照组比较,移植组MMP-9、hs-CRP及PAI-1水平明显降低(P<0.01)。结论 MSC移植可增加内皮细胞及胶原纤维数量,降低炎性因子及凝血纤溶因子,从而起到稳定与修复破裂斑块作用。     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.