沉默信息调节蛋白1在心肌缺血/再灌注中的保护作用

背景 沉默信息调节蛋白1 (silent information regulator protein 1,Sirt1)是尼克酰胺腺嘌呤二核苷酸(nicotinamide adenine dinucleotide,NAD)依赖的第3类组蛋白/非组蛋白去乙酰酶,参与细胞内多种生物功能的调节.Sirt1不仅在抗衰老中发挥重要作用,同样在心肌缺血/再灌注( ischemia/reperfusion,I/R)时保护受损细胞.目的 对Sirt1在心肌I/R中的保护机制以及几种激活Sirt1活性的方法进行综述. 内容 Sirt1能使活性氧清除剂产生增加、抗心肌细胞凋亡、促进细胞内自噬、减轻炎症反应、促进胞内正常线粒体合成等而减轻I/R的心肌细胞损伤.通过多种方法提高I/R时Sirt1的活性,是减轻损伤的重要措施. 趋向 随着Sin1在心肌I/R中的作用机制不断被揭示,其将成为缓解心肌I/R损伤的重要靶点.     

一次性便携式氧气流速调控瓶的研制

目的:研制一种能供医务人员适时调节氧气袋氧导管腔内氧气流速的一次性便携式氧气流速调控瓶.方法:在圆球形瓶体上开设2个互对的瓶口,将柔性氧气引入管及排氧管分别设置在2个互对的瓶口上,在柔性氧气引入管的进氧接口上增设一个调挡式氧流调节器.结果:该装置不仅能够防止因开启氧气袋氧导管的动作过猛或过大导致的氧气袋内极其有限的救生氧瞬间丢失或过快流失,而且能够防止开启氧导管过小导致的患者虚无吸氧.结论:该一次性便携式氧气流速调控瓶优于现有技术的一次性便携式氧气流速/湿化瓶,能够实现真正意义上的便携给氧和急救.     

Loss of inositol 1,4,5-trisphosphate receptors from bile duct epithelia is a common event in cholestasis

BACKGROUND AND AIMS: Cholestasis is one of the principal manifestations of liver disease and often results from disorders involving bile duct epithelia rather than hepatocytes. A range of disorders affects biliary epithelia, and no unifying pathophysiologic event in these cells has been identified as the cause of cholestasis. Here we examined the role of the inositol 1,4,5-trisphosphate receptor (InsP3R)/Ca(2+) release channel in Ca(2+) signaling and ductular secretion in animal models of cholestasis and in patients with cholestatic disorders. METHODS: The expression and distribution of the InsP3R and related proteins were examined in rat cholangiocytes before and after bile duct ligation or treatment with endotoxin. Ca(2+) signaling was examined in isolated bile ducts from these animals, whereas ductular bicarbonate secretion was examined in isolated perfused livers. Confocal immunofluorescence was used to examine cholangiocyte InsP3R expression in human liver biopsy specimens. RESULTS: Expression of the InsP3R was selectively lost from biliary epithelia after bile duct ligation or endotoxin treatment. As a result, Ca(2+) signaling and Ca(2+)-mediated bicarbonate secretion were lost as well, although other components of the Ca(2+) signaling pathway and adenosine 3',5'-cyclic monophosphate (cAMP)-mediated bicarbonate secretion both were preserved. Examination of human liver biopsy specimens showed that InsP3Rs also were lost from bile duct epithelia in a range of human cholestatic disorders, although InsP3R expression was intact in noncholestatic liver disease. CONCLUSIONS: InsP3-mediated Ca(2+) signaling in bile duct epithelia appears to be important for normal bile secretion in the liver, and loss of InsP3Rs may be a final common pathway for cholestasis.     

Induction of the monocytic differentiation of myeloid leukaemia cells by cotylenin A, a plant growth regulator

Regulators that play an important role in the differentiation and development of plants or invertebrates may also affect the differentiation of human leukaemia cells through a common signal transduction system, and might be clinically useful for treating acute myeloid leukaemia. Cotylenin A has been isolated as a plant growth regulator. We examined the effects of cotylenin A on the differentiation of several myelogenous leukaemia cells, and found that cotylenin A is a potent and novel inducer of the monocytic differentiation of human myeloid leukaemia cells. Cotylenin A induced the functional and morphological differentiation of myeloblastic and promyelocytic leukaemia cells, but did not effectively induce the differentiation of monocytoid leukaemia cells. Cotylenin A-induced differentiation was not affected by several inhibitors of signal transduction, suggesting that this inducer exhibits a unique mode of action.     

Effect of cerulein hyperstimulation on the paracellular barrier of rat exocrine pancreas

Cerulein-induced pancreatitis causes a rapid increase in pancreatic enzyme levels in serum and decreases in pancreatic duct secretion and interstitial edema. One mechanism to explain these early events is disruption of the actin tight junction paracellular seal of acinar and intralobular pancreatic duct cells. To examine the paracellular barrier of the proximal exocrine pancreas, rats were hyperstimulated with 5.0 μg · kg⁻¹ · h⁻¹ of cerulein. Actin was visualized with rhodamine phalloidin and by electron microscopy and tight junctions were visualized with antibodies to the tight-junction protein ZO-1. Paracellular permeability was measured by movement of horseradish peroxidase from interstitium into duct or acinar lumens. In controls, linear actin and ZO-1 staining occurred along the apical membrane of intralobular duct cells and extended to the apical pole of acinar cells. Hyperstimulation caused progressive disruption of the linear staining of f-actin and ZO-1. Actin disruption in duct cells was confirmed by electron microscopy. Horseradish peroxidase entered intralobular ducts and acinar lumens of hyperstimulated animals more frequently than those of controls. The structure and function of the paracellular barrier of acinar and intralobular pancreatic duct cells are disrupted early during cerulein pancreatitis and may contribute to early clinical features.     

胰腺导管系统对内分泌的功能影响及其可能机制

胰腺的内、外分泌系统在形态学和功能上存在密切联系.胰腺导管腔内的成分可能作用于一些直接开口于管腔的内分泌细胞,并通过内分泌细胞之间的缝隙连接,最终对更大量的内分泌细胞产生特殊的刺激.胰腺导管上皮细胞主要分泌富含碳酸氢钠（NaHCO3）的胰液,故胰液中NaHCO3可能对内分泌胰岛产生功能影响.研究表明囊性纤维化跨膜转导因子（cystic fibrosis transmembrane conductance regulator,CFTR）在胰腺导管上皮细胞大量表达,对分泌碳酸氢根（HCO3-）至关重要;但CFTR是否在内分泌胰岛表达仍有争议,在内分泌胰岛的作用更是鲜有研究.深入研究胰腺导管系统对内分泌胰腺功能上的影响及其机制,对糖尿病的防治及新药的开发具有积极意义.     

Identification and expression of iron regulators in human synovium: evidence for upregulation in haemophilic arthropathy compared to rheumatoid arthritis,osteoarthritis, and healthy controls

Recurrent joint bleeding is the most common manifestation of severe haemophilia resulting in haemophilic arthropathy (HA). Iron plays a central role in the pathogenesis of the two main features of HA: synovitis and cartilage destruction. The aim of this study was to investigate the synovial presence of the iron regulator proteins ferroportin (FPN), hepcidin, haemoglobin scavenger receptor CD163 (CD163), feline leukaemia virus subgroup C (FLVCR), and heme carrier protein 1 (HCP‐1). A comparison of the expression in HA with rheumatoid arthritis (RA), osteoarthritis (OA), and healthy controls (HC) is made. Synovial expression of iron regulators was investigated by immunohistochemistry in human synovial tissue and in a murine haemophilia model. We demonstrate for the first time the synovial presence of the investigated iron regulator proteins. Expression of the iron regulator proteins FPN, CD163, FLVCR, and HCP‐1 was enhanced in HA in comparison to RA, OA, and HC synovium. In addition, in a murine haemophilia model of acute joint bleeding, synovial expression of FPN, CD163, and HCP‐1 was increased. In both human and murine experiment, synovial expression of hepcidin was not altered. These findings indicate the presence of iron regulator proteins in the synovium, demonstrate an enhanced expression of FPN, CD163, FLVCR, and HCP‐1 in HA, and suggest a synovial adaptation mechanism to maintain synovial iron homeostasis in HA.     

HIV-1 Rev基因编码蛋白在PEL细胞系中的表达及其表达蛋白抑制HHV-8溶解性周期复制

目的:构建含人类免疫缺陷病毒1型(HIV-1)病毒颗粒蛋白表达调节因子(regulator of virion protein expression, Rev)编码基因的重组真核表达质粒并初步探索Rev基因编码蛋白对人类疱疹病毒8型(HHV-8)溶解性周期复制的影响.方法:构建pRev-Flag重组质粒并进行酶切鉴定和序列测定;将pRev-Flag重组质粒瞬时转染原发性渗出性淋巴瘤细胞系(PEL)BCBL-1细胞和小鼠胚胎成纤维细胞NIH/3T3,采用RT-PCR、Western blot分别从mRNA和蛋白水平检测Rev基因的表达情况;提取瞬时转染pRev-Flag重组质粒的BCBL-1细胞总RNA,进行RT-PCR检测HHV-8次要衣壳蛋白编码基因ORF26 mRNA转录水平.结果:核酸序列分析结果表明,克隆的Rev基因序列与GenBank中已登记的Rev序列100%同源.RT-PCR和Western blot都在Rev预期位置检测到特异性条带.RT-PCR检测显示,Rev基因对编码蛋白能够降低HHV-8 ORF26 mRNA转录水平.结论:成功构建含Rev基因序列的重组质粒并在真核细胞中获得正确表达;初步探索表明Rev蛋白能够抑制HHV-8溶解性周期复制.     

siRNA干扰SIRT1对辐射后IL-6表达的影响

目的 研究siRNA干扰沉默信息调节因子2相关酶1（SIRT1）对间充质干细胞（MSCs）电离辐射后诱导的炎性因子白细胞介素6（IL-6）的影响,探究SIRT1的辐射防护作用。 方法 使用0、2、4、8 Gy照射MSCs,分别在照后3、6、12、24 h提取总RNA和总蛋白,检测IL-6表达水平;将MSCs分为空白对照组、单纯照射组和SIRT1干扰联合照射组,使用Western blot、RT-PCR检测SIRT1和IL-6胞内表达。 结果 MSCs在电离照射后,IL-6的表达水平先升高后降低;在照后12 h达到最高,24 h恢复基准水平;而联合SIRT1干扰会引起IL-6水平进一步升高,加重MSCs电离辐射后的炎症反应。 结论 SIRT1可能通过抑制电离辐射诱导的炎性因子IL-6的表达,发挥辐射防护作用。