胰岛素抵抗性血管障碍分子水平发病机制研究进展

本文介绍胰岛素抵抗状态下内皮机能障碍发生机制的最新研究进展。一些研究表明,在胰岛素抵抗状态下,因血管壁肾素—血管紧张素系统机能亢进,导致了血管张力增加,另外,又因血管内皮嘌呤代谢异常,导致了内皮型一氧化氮合成酶(eNOS)脱耦联及功能异常,使经 eNOS 途径生成的 O_2~- 增多,而 NO 生成减少。此为引起血管内皮机能损害的机制之一。     

非诺贝特促进人内皮细胞内皮一氧化氮合酶复偶联的作用研究

目的探讨非诺贝特能否对脂多糖（LPS）诱导的血管内皮一氧化氮合酶（eNOS）脱偶联发挥保护作用。方法体外培养人脐静脉内皮细胞（HUVECs）,用非诺贝特预处理HUVECs 2 h,再与LPS共孵育24 h,采用高效液相色谱法检测细胞四氢生物蝶呤（BH4）的表达水平,ELISA检测细胞eNOS表达水平和细胞上清一氧化氮（NO）浓度,利用Confocal方法检测细胞内活性氧（ROS）产生水平。结果与对照组比较,单纯LPS刺激组内皮细胞BH4表达水平降低,伴有eNOS表达下调和NO水平降低,而内皮细胞内ROS产生增加（P均〈0.05）。与单纯LPS刺激组比较,非诺贝特预处理组内皮细胞BH4表达水平升高,同时伴有eNOS表达上调和NO水平增加,而内皮细胞内ROS产生降低（P均〈0.05）。结论非诺贝特通过上调BH4水平,对LPS诱导的血管内皮细胞eNOS脱偶联有逆转作用,这可能是其发挥血管内皮保护作用的机制之一。     

ApoAⅠ/ABCA1通过STAT3/TTP途径调节炎症因子mRNA降解

目的增龄伴随着血管结构和功能的改变及相关内皮细胞的损害,是动脉粥样硬化血管疾病发生发展的独立危险因素之一。加强增龄有关的内皮功能障碍的研究,对老年人心、脑血管疾病的防治有着重要意义。本研究通过观察增龄对大鼠血管结构和内皮功能的影响,探讨增龄所致的血管内皮功能障碍及其可能机制,为进一步研究如何早期延缓增龄性内皮功能障碍提供新思路。方法选择青年组(3月龄)、成年组(9月龄)、中年组(15月龄)健康雄性大鼠,通过检测血管内皮功能相关指标(血浆NO、eNOS、iNOS、ET-1及主动脉组织NO、eNOS、iNOS),测定离体主动脉环内皮依赖性与非内皮依赖性血管舒张功能,观察大鼠主动脉的形态学变化,寻找出早期出现内皮功能明显改变的月龄组大鼠。结果青年组、成年组、中年组大鼠血浆NO、eNOS、iNOS及主动脉组织的NOS活性随月龄增加逐渐降低(P<0.05),NO、eNOS、iNOS与月龄呈负相关;ET-1则逐渐升高(P<0.05),ET-1与月龄呈正相关;主动脉环对于乙酰胆碱所致的最大血管舒张程度随着月龄增加降低(P<0.05),对硝普钠所致的舒张反应各组基本一致(P>0.05);主动脉形态随着月龄的增加,内膜中膜厚度...     

NO的合成和NO的血管效应

一氧化氮(NO)是通过激活内皮型NO合酶(eNOS)进行调节的,是对内皮细胞中胞浆钙离子浓度增加反应的产物;钙离子与钙调节蛋白结合以后激活eNOS。实验已经证明钙离子中载体A23187可以导致内皮细胞钙离子浓度的增加,随后血管平滑肌细胞钙离子浓度减少〔1〕。有趣的是,这些效应在高血压鼠的肾动脉比正常血压鼠肾动脉要低。在几种心血管疾病中,如高血压发现内皮功能失调可以导致NO缺失。NO已经作为     

专题报告

背景和目的血管新生在整个生命过程中都发挥着关键的作用,但是随着年龄的增长,老年个体的血管新生功能呈现进程性减弱,修复缺血和受损组织的能力显著降低。内皮祖细胞(EPC)已被证实在成体的血管新生中起重要作用,来源于老年个体的EPC其增殖、存活及迁移功能明显减弱。最近的研究表明miRNA参与了血管新生的调控。miR-34a是肿瘤抑制因子,通过作用于靶蛋白沉默信息调控子1(SIRT1)导致细胞周期阻滞或者细胞凋亡。但是,目前尚不清楚miR-34a是否在EPC介导的血管新生中起作用。此外,最近已报道miR-34a在老年小鼠的心脏和脾脏中水平升高,提示衰老可上调miR-34a水平。EPC还受到eNOS的调控,在衰老的情况下eNOS的功能也被削弱。研究已证明,eNOS的必需辅因子BH4水平的下降可引起eNOS解偶联,导致EPC的数量及迁移能力降低。GTP水解酶I(GTPCH I)是生理情况下合成BH4的限速酶。GTPCH I活性的降低可减少BH4的产生,引起eNOS解偶联,从而导致活性氧(ROS)水平升高。但是EPC中的GTPCHI是否可以通过影响ROS的产生进而调控miR-34a的表达尚不清楚。本研究旨在探讨正常与衰老情...     

人内皮型一氧化氮合酶重组腺病毒在小鼠肺内表达

一氧化氮合酶（NOS）是合成一氧化氮（NO）的关键酶，主要包括3个亚型：神经型（nNOS）、诱导型（iNOS）、内皮型（eNOS）。eNOS主要分布于血管内皮，通过催化NO的生成而在调节血管壁张力及维持血管壁构型方面发挥重要作用。各种引起内皮功能受损的原因均可使NOS生成减少，导致NO生成不足，破坏体内内皮素1／一氧化氮（ET-1／NO）的平衡。本研究从人脐静脉血管内皮成功克隆出人eNOS（heNOS）eDNA全长基因的基础上，构建了复制能力缺陷型heNOS重组腺病毒转移载体，并对其功能和转移途径进行初步研究，旨在探讨从基因角度补充NOS以维持体内ET-1／NO平衡，治疗因NO不足而导致的血管损伤性疾病的可能性。     

麝香保心丸对高同型半胱氨酸血症大鼠内皮功能的影响

目的在大鼠高同型半胱氨酸血症(HHcy)模型上,探讨麝香保心丸对血管内皮功能的影响。方法将24只雄性SD大鼠随机分为正常对照组、HHcy组及HHcy+麝香保心丸组,每组8只。采用酶联免疫吸附法(ELISA)检测血浆同型半胱氨酸(Hcy)水平,采用硝酸还原酶法检测大鼠血浆一氧化氮(NO)含量,采用免疫组织化学法检测主动脉一氧化氮合成酶(eNOS)表达。结果 L-蛋氨酸灌胃能够诱导大鼠HHcy模型,使血浆NO含量减少,血管内皮eNOS表达同步下调;采用麝香保心丸干预后,内皮功能有所改善。结论麝香保心丸可改善HHcy引起的内皮功能障碍。     

不对称二甲基精氨酸与心血管疾病关系的研究进展

不对称二甲基精氨酸(ADMA)是精氨酸甲基化衍生物,由甲基化蛋白生理降解而成。ADMA是主要的内源性一氧化氮合酶(NOS)抑制剂,该酶为合成一氧化氮(NO)所需,具有重要的抗动脉粥样硬化特性。血浆ADMA浓度升高会造成NO合成受损,导致血管内皮功能障碍和动脉粥样硬化性血管疾病。     

慢性间歇低氧对大鼠血管内皮功能的影响以及抗氧化剂干预作用

目的 通过测定血清中血管活性物质,探讨慢性间歇低氧(CIH)对大鼠血管内皮功能的影响,以及抗氧化剂4-羟基-2,2,6,6四甲基哌啶(Tempol)的防治作用.方法 将48只Wistar雄性大鼠随机分为6组,每组8只,包括常氧对照组(NC组)、间歇低氧组(IH组)和4组间歇低氧Tempol干预及其对照组:IHT1组、IHT2组、IHN1组、IHN2组.IHT1、IHT2组分别为实验前和实验后第28天给予10％ Tempol100mg· kg-1·d-1腹腔注射,IHN1、IHN2组于相同时间给予等量生理盐水腹腔注射.结果 IHT2组与IHN2组比较,ET-1水平显著降低(P＜0.05),NO、eNOS水平升高(P值均＜0.05);但ET-1水平仍高于NC组(P＜0.01),NO、eNOS较其降低(P值均＜0.01).IHT1组ET-1水平低于IHT2组(P＜0.01),NO、eNOS水平较其升高(P值均＜0.01);各指标与NC组差异无统计学意义.IH组与IHN1组、IHN2组相比,各指标差异均无统计学意义.结论 CIH可能通过氧化应激引起血清ET-1、NO含量失衡,导致内皮功能障碍.抗氧化剂Tempol可减轻血管内皮氧化应激损伤,在改善血管内皮功能方面具有一定的意义.     

X综合征患者血管内分泌功能和内皮依赖性舒张功能障碍的研究

目的　研究内皮依赖性舒张功能障碍在X综合征患者发病中的意义。方法　对 18例X综合征患者和 2 0例正常对照者 ,采用高分辨多普勒超声仪测定肱动脉基础、反应性充血和舌下含服硝酸甘油后血管舒张末期内径变化 ,并测定血浆内皮素 (ET)、一氧化氮 (NO)含量。结果　 (1)X综合征患者肱动脉血流介导的血管扩张较对照组明显减弱 ,含服硝酸甘油后血管明显扩张 ,但两组无显著差异 ;(2 )X综合征组较对照组ET水平显著升高 ,NO水平显著降低 ;(3)肱动脉血流介导的血管扩张与血浆ET水平呈显著负相关 ,与NO水平呈显著正相关。结论　X综合征患者存在血管内分泌功能紊乱、内皮依赖性舒张功能障碍 ,后者与内皮源性松弛因子减少有关。     

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.     

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.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.