沉默信息调节因子T1在心血管疾病中的作用

细胞生物学的最新进展表明沉默信息调节因子2(SIR2)相关酶类在心脏应激条件下的病理生理机制中扮演着重要角色。目前大部分物种均存在SIR2同源基因,统称为sirtuins(SIRT)家族,其中研究最广泛的是沉默信息调节因子T1(SIRT1),它是许多心血管疾病发生和发展的关键调节因子。本文综述了SIRT1的基本特征以及其在心血管疾病中的作用及可能机制,为心血管疾病的预防、诊断和治疗提供了新的思路。     

血清沉默信息调节因子2相关酶1和血浆核因子E2相关因子与原发性高血压早期心脏损伤的关系

目的 探讨血清沉默信息调节因子2相关酶1(SIRT1)和血浆核因子E2相关因子(NRF2)与原发性高血压早期心脏损伤的关系及其预测心脏损伤的效能。方法 纳入安阳市第三人民医院2020年1月至2022年1月收治的原发性高血压患者150例,以心肌肌钙蛋白(CTnI)诊断心脏损伤,依据患者是否伴有早期心脏损伤将患者分为心脏损伤组以及对照组(不伴心脏损伤),各75例。检测各患者的血清SIRT1、NRF2水平并进行分析,采用多因素logistic回归模型分析SIRT1、NRF2与原发性高血压早期心脏损伤的关系,绘制受试者工作特征(ROC)曲线评估SIRT1、NRF2对原发性高血压早期心脏损伤的诊断价值。结果 心脏损伤组血清SIRT1、NRF2水平低于对照组(t=13.034,8.671,P<0.05)。多因素logistic回归分析结果显示,血清SIRT1、NRF2水平、高密度脂蛋白胆固醇(HDL-C)水平是原发性高血压早期心脏损伤的独立保护因素(P<0.05),甘油三酯、左室射血分数、血清晚期氧化蛋白产物、丙二醛、C反应蛋白、肿瘤坏死因子α、白细胞介素-6、低密度脂蛋白胆固醇、总胆...     

SIRT1基因启动子DNA甲基化在老年钙化性心脏瓣膜病中的临床意义研究

[摘 要] 目的 探讨沉默信息调节因子1（SIRT1）基因启动子区域DNA甲基化修饰变化与老年钙化性心脏瓣膜病的相关性。方法 选取我院 2020年2月 ~ 2021年1月就诊的老年钙化性心脏瓣膜病患者60例,另纳入同期体检的健康老年40例作为对照。甲基化特异性PCR检测SIRT1基因启动子区域甲基化率,荧光定量PCR检测SIRT1 mRNA表达,ELISA检测SIRT1蛋白和NF-κB蛋白表达。结果 观察组SIRT1基因启动子区域甲基化率为63.3%（38/60）,显著高于对照组的37.5%（15/40）（P<0.01）。甲基化组SIRT1 mRNA的2-△△Ct值为0.22±0.05,显著低于非甲基化组的0.36±0.07（P<0.01）,甲基化组SIRT1 蛋白表达水平为82.34±11.56 μmol/L,显著低于非甲基化组的143.24±18.73 μmol/L（P<0.01）,甲基化组NF-κB蛋白表达水平为126.48±17.32 μmol/L,显著高于非甲基化组的41.53±7.26 μmol/L（P<0.01）。老年钙化性心脏瓣膜病SIRT1 mRNA与NF-κB蛋白表达呈显著负相关（P<0.05）,SIRT1蛋白表达与NF-κB蛋白表达呈显著负相关（P<0.05）。结论 老年钙化性心脏瓣膜病患者SIRT1基因启动子区域高甲基化变化,导致SIRT1表达减低,激活炎症反应,可能参与其致病过程。     

SIRT1与血管性疾病的研究进展

沉默信息调节因子2相关酶1 (SIRT1)是一种高度保守的NAD+依赖的第Ⅲ类组蛋白去乙酰化酶,主要通过翻译后修饰调节DNA损伤修复、氧化应激、炎症、细胞衰老、凋亡与增殖等,从而参与血管性疾病的发生发展.因此,SIRT1可能成为治疗血管性疾病的潜在靶点.本文主要对SIRT1的主要生理作用及其在动脉粥样硬化、高血压、肺动脉高压、糖尿病肾病及糖尿病视网膜病变等常见血管性疾病中的作用作一综述.     

心脏铁代谢及其相关疾病研究进展

铁是一切生物体所必需的微量元素。它参与细胞的增殖和分化 ,通过催化氧化 还原反应参与电子传递、细胞呼吸、能量代谢、解毒等许多重要生理过程 ,以及调节一氧化氮合酶 ,ＰＫＣ β、ｐ2 1等与细胞生长和功能有关的基因表达[1 ] 。近年来 ,铁超载在心脏疾病中的作用越来越受到重视。本文将介绍一些主要参与心脏铁代谢的蛋白及其功能和调节 ,以及目前对铁诱导的心肌损伤在心肌缺血 再灌注、血色病、β 地中海贫血和冠脉粥样硬化等心脏疾病中作用的认识。一、铁在心脏的分布、关系及功能正常成人体内铁的总量为 3～ 4ｇ。体内的铁可分为两大…     

瞬时受体电位C通道与心肌肥厚的研究进展

瞬时受体电位C(transient receptor potential canonical,TRPC)通道作为一类重要的非选择性阳离子通道，在心脏具有广泛的分布和表达。TRPC通道通过改变细胞膜电位和介导钙离子(Ca2+)内流对心脏的生理和病理反应产生重要影响。细胞内Ca2+不仅在心肌细胞的兴奋-收缩偶联中发挥重要作用，而且与各类心脏疾病发生密切相关。最近研究发现，TRPC通道可以通过调节细胞内Ca2+变化，与钙调磷酸酶(calcineurin,CaN)和活化的T细胞核因子(nuclear factor of activated T cells,NFAT)等效应因子参与心肌肥厚的发生发展过程，同时可诱导其他心脏疾病（如心肌纤维化、心率失常、心力衰竭）的发生。本文根据相关研究，围绕TRPC通道在心肌肥厚及相关心脏疾病的发生发展中的作用进行总结回顾。     

新一代CT为什么能做心脏的检查？

CT自发明30年来发生了巨大的变化,而具有临床诊断意义的进步是:新一代CT已实现了以往CT检查盲区的突破,能够对心脏和心脏血管进行检查,这是30年来CT技术方面的重要贡献之一.简而言之,当今CT技术的发展并且能够做心脏方面的检查,其主要原因可归纳为两个方面:1.硬件制造技术的进步;2.临床应用软件的发展.     

SIRT1在支气管哮喘中的研究进展

正沉默信息调节因子2(Sirt2)是1986年Ivy等人在酵母菌中发现的和长寿相关的基因[1],后来发现在哺乳动物中也存在和Sirt2同源蛋白,命名为SIRT1-SIRT7,其中SIRT1和酵母的Sirt2同源性最高。SIRT1作为细胞内重要的调节因子,广泛分布于人类多种细胞的胞浆和胞核,参与调节炎症、细胞周期、衰老和凋亡、应激等重要生理过程。与多种肺部疾病的发生发展密切相关,例如慢性阻塞性肺疾     

SIRT1与代谢及肿瘤的关系

沉默信息调节因子1(SIRT1)是一种依赖烟酰胺腺嘌呤二核苷酸(NAD+)的去乙酰化酶,它在正常的胚胎发育、分化及维持自身平衡中是必不可少的.SIRT1在维持健康及疾病中发挥着很多重要的作用,包括SIRT1在基因组稳定性中的作用[1],在时钟调节下的基因组重构及昼夜节律控制中的作用[2],以及神经元基因和阿尔茨海默病之间关系的调节作用[3].之前也有很多有关健康及疾病中SIRT1的综述[4,5].作为sirtuin家族中一员,SIRT1表现出了对氧化还原代谢物NAD+先天的辅酶需求.这与SIRT1控制关键代谢调节的能力一起,证明了SIRT1在哺乳动物代谢中即是一个感受器,又是一个调节器.SIRT1的大多数功能是通过对基因表达过程中起关键作用的调节蛋白针对性的去乙酰化实现的.SIRT1的作用靶点包括转录因子及代谢调节中的辅酶因子.我们对SIRT1活性与代谢稳态关系的最新研究进展作一综述,并且基于细胞生存中SIRT1的作用,我们研究了相应的治疗方法.     

SIRT1与糖尿病相关肿瘤的关系

糖尿病不仅增加肿瘤的患病风险,而且促进肿瘤的复发和转移.沉默信息调节因子1(SIRT1)是机体的能量感受器,具有调节糖、脂代谢,抑制慢性非特异性炎性反应,改善胰岛素抵抗等作用,其表达及活性异常参与了糖尿病及其并发症的发生.同时近期研究发现SIRT1也与肿瘤的发生、发展密切相关.通过去乙酰化调节机制SIRT1可调控大量转录因子及组蛋白的活性,从而参与染色质沉默、细胞凋亡、自噬途径及DNA损伤修复的调控,是联系细胞能量代谢与染色质结构的关键蛋白,因而可能是联系糖尿病及糖尿病相关肿瘤的重要中介.积极干预糖尿病患者中SIRT1信号途径异常,可能具有降低肿瘤风险的作用.     

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.     

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.     

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.     

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.