氨氯地平对实验性兔动脉粥样硬化进程中一氧化氮合酶—一氧化氮和血红素氧合酶—一氧化碳系统的影响

目的探讨血红素氧合酶—一氧化碳和一氧化氮合酶—一氧化氮系统在动脉粥样硬化中的变化、相互关系及氨氯地平对动脉粥样硬化进程中血红素氧合酶—一氧化碳和一氧化氮合酶—一氧化氮的影响。方法家兔予以高胆固醇饮食8周,8周后停用高胆固醇饮食或另外给予喂饲氨氯地平进行药物干预8周。结果与对照组比较,模型组血脂水平明显升高,血清一氧化氮含量明显降低,血浆一氧化碳水平明显升高,血红素氧合酶1及诱导型一氧化氮合酶表达明显升高(P均<0.01)。与模型组比较,氨氯地平组血浆胆固醇、甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇差异无显著性(P>0.05);血清一氧化氮含量差异亦无显著性(P>0.05),血浆一氧化碳水平明显降低(P<0.01),血红素氧合酶1及诱导型一氧化氮合酶表达明显减少(P<0.01)。结论动脉粥样硬化进程中,血红素氧合酶—一氧化碳和一氧化氮合酶—一氧化氮系统显示出互补及代偿性调节作用,氨氯地平可以通过下调血红素氧合酶—一氧化碳和一氧化氮合酶—一氧化氮系统而延缓动脉粥样硬化的进程。     

血红素氧合酶1—一氧化碳和一氧化氮合酶1—一氧化氮系统在动脉粥样硬化中的作用及其相关性研究

目的探讨血红素氧合酶1-一氧化碳和诱生型一氧化氮合酶-一氧化氮在动脉粥样硬化中的变化、相互关系及对动脉粥样硬化进程的影响. 方法家兔予以高胆固醇饮食(n=8)以及在高胆固醇饮食的同时经饮水给予L-精氨酸(n=8)或L-亚硝基精氨酸甲酯(n=8),或经腹腔注射血红素-L-赖氨酸盐(n=8)或锌原卟啉-9(n=8),共10周.结果与对照组比较,胆固醇组主动脉一氧化氮生成量显著减少,一氧化碳生成量则明显增加,一氧化氮合酶活性显著降低(P均<0.01),而血红素氧合酶1表达升高,主动脉斑块面积达40.2%±8.9%.与胆固醇组比较,外源性血红素-L-赖氨酸盐干预组的主动脉内膜斑块面积(26.6%±9.2%)明显缩小,主动脉一氧化碳的生成量和血红素氧合酶1的表达明显升高(P<0.01),但一氧化氮合酶活性和一氧化氮生成量较正常对照组显著降低(P<0.01),与胆固醇组比较则无显著性差异(P>0.05);与胆固醇组比较,外源性L-精氨酸组主动脉一氧化氮合酶活性显著升高, 一氧化氮生成量增加,主动脉斑块面积(28.1%±7.7%)明显缩小(P均<0.01),而血红素氧合酶1的表达和一氧化碳的生成较正常对照组明显升高,与胆固醇组比较则无显著性差异(P>0.05).与胆固醇组比较,血红素-L-赖氨酸盐干预组、L-精氨酸组的主动脉组织内c-myc及c-fos的mRNA和蛋白表达均显著降低(P均<0.01),而锌原卟啉组和L-亚硝基精氨酸甲酯组则无明显差异.结论动脉粥样硬化进程中,血红素氧合酶/一氧化碳和一氧化氮合酶/一氧化氮系统显示出互补及代偿性调节作用,血红素氧合酶系统通过对一氧化氮和一氧化氮合酶的调节和代偿机制抑制动脉粥样硬化病变的发展.     

实验性兔动脉粥样硬化发病过程中内源性一氧化碳及其合成酶基因表达的改变

为研究内源性一氧化碳及其合成酶血红素氧化酶１在动脉粥样硬化发病中的变化规律,通过逆转录－聚合酶链反应、原位杂交、免疫组织化学染色和生物化学等多项指标观察血红素氧化酶１和内源性一氧化碳在动脉粥样硬化发病过程中的变化。结果发现,血红素氧化酶１ｍＲＮＡ主要分布于主动脉和冠状动脉内皮细胞,在动脉粥样硬化的发展过程中其表达有逐渐增高的趋势,且血红素氧化酶１蛋白的表达也有逐渐增高的趋势。血红素氧化酶１免疫组织化学染色显示,主动脉和冠状动脉内皮细胞呈阳性,主动脉壁血红素氧化酶１ｍＲＮＡ的表达量及血红素氧化酶活性和内源性一氧化碳的浓度有逐渐增高的趋势。结果提示,内源性一氧化碳及其合成酶在动脉粥样硬化的发病过程中可能具有重要的作用。     

实验性兔动脉粥样硬化发病过程中内源性一氧化碳及其合成酶基？…

为研究内源性一氧化碳及其合成酶血红素氧化酶－１在动脉粥样硬化发病中的变化规律,通过逆转录－聚合酶链反应,原位杂交,免疫组织化学染色和生物化学等多项指标观察血红素氧化酶－１和内源性一氧化碳在动脉粥样硬化发病过程中的变化。     

血红素氧合酶-1抗动脉粥样硬化作用与机制的研究进展

血红素氧合酶-1是细胞内一种极其重要的可诱导型抗氧化酶,它主要作为限速酶催化细胞内具有促氧化性质的游离血红素降解生成胆绿素(随即被还原成胆红素)、一氧化碳和Fe2+。目前研究证实,血红素氧合酶-1/胆红素/一氧化碳共同组成的内源性保护系统在机体组织细胞应对炎症与氧化应激损伤中不可或缺,上调血红素氧合酶-1表达可以通过多种机制抑制动脉粥样硬化的发生和发展,从而可能成为今后防治动脉粥样硬化相关性疾病的新靶点。     

血红素氧合酶1/一氧化碳系统对球囊损伤后内膜增殖及内皮功能的影响

目的 探讨血红素氧合酶1/一氧化碳((HO-1)/CO)系统对兔颈动脉球囊损伤后内膜增殖及内皮功能的影响及其可能的作用机制.方法 家兔随机分为对照组、胆固醇组、血红素组、卟啉锌组和假手术组5组,每组10只.对照组予普通饮食,其余4组喂饲含1.5%胆固醇饲料,血红素组和卟啉锌组同时分别予氯化血红素或锌原卟啉9腹腔内注射,2周后实验组行颈总动脉球囊损伤术,术后续原喂养给药8周.结果 高胆固醇饮食血脂(总胆固醇、甘油三酯、低密度脂蛋白、氧化型低密度脂蛋白)水平显著升高(P<0.01).与对照组比较,胆固醇组颈动脉一氧化氮生成量、cNOS活性显著降低,而一氧化碳生成量、血红素氧合酶活性显著增加(P均<0.01),内膜面积和内膜/中膜面积比值为(0.586±0.090比1.381±0.180).与胆固醇组比较,氯化血红素干预显著增加血红素氧合酶活性、一氧化碳生成量,显著降低内皮素1水平,内膜面积和内膜/中膜面积比值最小(0.386±0.076比0.862±0.164;P均<0.01);锌原卟啉9显著抑制血红素氧合酶活性、一氧化碳生成量,显著增高内皮素1水平,内膜面积和内膜/中膜面积比值最大(0.734±0.096比1.843±0.212),差异均有显著性(P<0.01).结论 高胆固醇饮食加球囊损伤严重损害颈动脉NOS/NO系统,血红素氧合酶1/一氧化碳系统通过代偿和调节NOS/NO系统及降低内皮素1表达从而改善内皮功能,抑制血管损伤后内膜增殖和不良重塑.     

血红素加氧酶/一氧化碳在血管平滑肌细胞中的研究

血红素加氧酶是哺乳动物中血红素代谢的限速酶,它能分解血红素成胆绿素、一氧化碳和铁.其中血红素加氧酶-1又称诱导型血红素加氧酶,它在血管平滑肌细胞中表达,可以被诸多因素所诱导.由血红素加氧酶-1催化产生的一氧化碳是一种重要的内源性生物信使,目前研究已经表明了它在循环系统中的重要作用.血管平滑肌细胞的增殖和凋亡是众多的心血管疾病如高血压、动脉粥样硬化的病理基础.血红素加氧酶/一氧化碳系统与血管平滑肌细胞的增殖和凋亡有着密切的关系.目前研究发现不少心血管药物通过该系统影响平滑肌细胞的增殖和凋亡,为新药物的开发奠定了基础.     

血红素氧合酶1的抗氧化生理特性在动脉粥样硬化中的作用

血红素氧合酶1通过降解血红素产生一氧化碳、胆绿素和铁离子。胆绿素经胆绿素还原酶作用生成胆红素,铁离子可诱导铁蛋白合成。上述产物具有抗氧化和细胞保护作用,使血红素氧合酶-1在维持机体内环境氧化和抗氧化平衡方面具有独特意义。大量证据显示,血红素氧合酶-1具有抗动脉粥样硬化作用。对血红素氧合酶-1表达的调控极有可能成为将来用基因疗法来防治动脉粥样硬化疾病的一个新靶点。     

血红素氧合酶-1与冠状动脉粥样硬化斑块的稳定性

随着对冠脉综合征研究的深入,我们发现冠脉病变的严重程度主要是由斑块的稳定性决定的。血红素氧合酶是血红素降解的起始酶和限速酶,能代谢血红素形成一氧化碳、游离铁和胆红素。近来研究表明血红素氧合酶-1参与了动脉粥样硬化的发生、发展,与斑块稳定性有着密切的关系。     

内源性一氧化氮及一氧化碳的改变对家兔动脉粥样硬化进程的影响

目的　探讨主动脉内源性一氧化氮(NO)及一氧化碳(CO)在高胆固醇饮食诱导的动脉粥样硬化(AS)中的变化及对AS进程的影响。方法　家兔予以高胆固醇饮食(胆固醇组,n=7)以及在高胆固醇饮食的同时经饮水给予L-精氨酸(精氨酸组,n=9)或腹腔注射血红素-L-赖氨酸盐(血红素组,n=9),共10周。结果　高胆固醇饮食对血浆L-精氨酸水平无明显影响,但显著升高血清总胆固醇、血浆非对称性二甲基精氨酸及ox-LDL浓度。与对照组(n=6)比较,胆固醇组主动脉NO及CO生成量显著减少,NO合成酶(cNOS)及血红素加氧酶(HO)活性显著降低(P均<0.01),主动脉斑块面积达(42.6±9.2)%。与胆固醇组比较,外源性L-精氨酸显著升高血浆L-精氨酸水平及主动脉cNOS活性,增加NO生成量(P均<0.01),主动脉斑块面积仅(19.5±7.4)%(P<0.05);外源性血红素-L-赖氨酸盐恢复了主动脉CO生成量(P<0.01),主动脉斑块面积为(28.4±8.1)%(P<0.05)。结论　高胆固醇饮食诱导的AS显著损害了主动脉NOS/NO及HO/CO系统,内源性NO及CO生成量减少与AS的发生发展密切相关。L-精氨酸及血红素-L-赖氨酸盐分别通过增加主动脉NO及CO生成量而抑制AS进展。     

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.