PCBP1:一种在多水平上参与基因表达调控的蛋白因子

多聚胞嘧啶结合蛋白1 (poly C binding protein-1,PCBP1),属于RNA结合蛋白亚家族,因其具有同RNA的多聚胞嘧啶(poly C)区域特异的结合活性而得名.目前该亚家族共有5个成员:hnRNP K(heterogeneous nuclear ribonucleoprotein K)、PCBP1、PCBP2、PCBP3和PCBP4.PCBP1蛋白在多个水平参与基因的表达调控,如转录、mRNA加工、mRNA的转运、mRNA稳定以及翻译水平调控等.本文对PCBP1基因的结构和生物学功能进行了综述.     

糖尿病大鼠骨折后骨形态发生蛋白-2、胰岛素样生长因子-1的变化

目的 观察糖尿病大鼠骨折后骨形态发生蛋白-2(BMP-2)、胰岛素样生长因子-1(IGF-1)的变化,探讨糖尿病对骨折愈合的影响.方法 70只大鼠随机分为对照组和糖尿病组,均造成左侧胫骨骨折.定期摄X线片,取骨痂HE染色,免疫组化检测骨痂BMP-2、IGF-1,ELISA法检测血清BMP-2、IGF-1.结果 2周BMP-2灰度值:实验组为149±8,对照组为107±7(P＜0.01);2周IGF-1灰度值:实验组为137±9,对照组为103±8(P＜0.01).2周血清BMP-2含量:实验组为(3.45±0.12) ng/ml,对照组为(5.60±0.11) ng/ml(P＜0.01);2周IGF-1含量:实验组为(5.89±0.12) ng/ml,对照组为(8.36±0.11) ng/ml(P＜0.01).结论 糖尿病大鼠骨折后血清及骨痂中BMP-2、IGF-1减少是导致糖尿病大鼠骨折愈合差的原因之一;BMP-2与IGF-1可能存在相互作用.     

异体脱钙骨基质复合bBMP修复兔桡骨骨缺损

目的：探讨异体脱钙骨基质复合BMP修复节段性骨缺损的能力。方法：64只新西兰大白兔采用桡骨15mm节段性骨缺损模型，随机分为4组，A组植入异体脱钙骨基质(Demineralized Bone Matrix,DBM)与牛骨形态发生蛋白(Bovine Bone Morphogentic Protein,bBMP)复合材料，B组植入异体DBIM，C组植入异体骨粒，D组为空白对照组。术后4、8、12、16w，进行放射学检查、病理组织学检查和计算机图像分析新生骨面积。结果：异体DBM与bBMP复合材料组骨生成、新骨面积和骨连接情况明显优于异体DBM组、异体骨粒组和空白对照组。结论：异体DBM复合BMP材料通过骨诱导和骨传导两种方式修复骨缺损，是一种较为理想、具有高效成骨活性的植骨材料。     

The heat shock/oxidative stress connection

Involvement of free-radical oxidations in the aging process has been a topic of interest since Harman's original contribution. Because of the close association between aging and Alzheimer disease (AD) and the qualitative similarity in the neuropathology of both conditions, it has been proposed by many investigators that oxidative stress may be important in AD. If such modality of injury was indeed involved, one should expect to find markers of oxidation and heat shock (since free radicals are key mediators of heat-shock induction) in brains of patients with AD. In fact, several studies documented abnormal expression of antioxidant enzymes and heat-shock proteins (HSP) along with other markers of oxidation in AD brains. We showed that abnormally expressed antioxidant enzymes are topographically associated with senile plaques and neurofibrillary tangles, and that the activity of these enzymes is (contrary to what one would expect) markedly reduced. These findings have recently been confirmed by other investigators. Despite a large amount of evidence that suggests an association between oxidative stress and the pathogenesis of AD, it is not yet known whether oxidative stress is a cause or consequence of the disorder. Future research efforts regarding the oxidative stress hypothesis of AD should include attempts, at generating AD pathology by oxidative means in laboratory animals, determining the role and integrity of the heat-shock response in AD, as well as that of various antioxidant systems, growth factors, and hormones with antioxidant and neuroprotective properties.     

Daily variation in circulating cytokines and acute-phase proteins correlates with clinical and laboratory indices in community-acquired pneumonia

Our objective was to investigate the initial levels of circulating proinflammatory cytokines, such as interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumour necrosis factor alpha (TNF-α), of certain acute-phase proteins, such as C-reactive protein (CRP), fibrinogen (FBN) and albumin, and of the glycoprotein fibronectin at presentation and their daily variation during the clinical course of community-acquired pneumonia (CAP) in relation to clinical and laboratory indices of infection. Thirty otherwise healthy hospitalized patients aged 48 ± 3 years (mean ± SEM) and with bacteriologically confirmed CAP were studied prospectively. IL-1β and IL-6 were found to be 15-fold higher on admission (122 ± 9 pg mL^?1 and 60 ± 4 pg mL^?1 respectively), whereas TNF-α was three-fold higher (102 ± 5 pg mL^?1) than those of controls, all of them showing a decline towards normal. Initial CRP levels were increased 90-fold (416 ± 1 mg L^?1), whereas fibronectin levels were reduced (242 ± 9 mg dL^?1). The presence of parapneumonic effusion was associated with a higher TNF-α serum level (127 ± 7 vs. 86 ± 4 pg mL^?1, P = 0.0002), a more rapid daily decline in TNF-α (–7.2 ± 0.7 vs. ?3.8 ± 0.5 pg mL^?1 day^?1, P = 0.0005), a slower rate of decline in CRP (?42.8 ± 3.0 vs. ?54.6 ± 3.0 mg L^?1 day^?1, P = 0.02) and a slower rate of increase in FBN (5.9 ± 1.0 vs. 11.7 ± 1.0 mg dL^?1 day^?1), P = 0.001]. Furthermore, daily progression of serum levels of cytokines and acute-phase proteins correlated strongly with pyrexia, erythrocyte sedimentation rate (ESR), neutrophil count, alveolar–arterial oxygen difference and radiographic resolution, clinically manifested by improvement in the patients' condition.     

Comparison of salivary calmodulin binding proteins in Sjögren''s syndrome and healthy individuals

Background: Reduction in salivary secretion is the hallmark of Sjögren's syndrome (SS). Calmodulin (CaM) and calmodulin binding proteins (CaMBPs) play a key role in the secretory process of saliva. Recent studies have suggested that SS‐B, an autoantibody associated with SS, is a CaMBP. This finding suggests that CaMBP may contribute to the loss of saliva in SS. To better understand the role(s) of these proteins in SS, the purpose of this study was to compare salivary CaMBPs in Sjögren's patients and controls. Methods: Saliva samples were collected from 20 patients and 20 age‐, race‐, and gender‐matched controls. CaM overlay was used to identify CaMBPs in saliva of patients and controls. Results: Higher number of salivary CaMBPs was observed among patients than controls. Conclusions: The increased number of salivary CaMBPs in SS may suggest a potential role for these proteins in the pathogenesis of the disease.     

停跳或不停跳心脏手术对血清 S-100B蛋白表达的影响

【目的】研究心脏手术围术期血清S-100B蛋白表达及其与停跳或不停跳心肺转流方式和时间的关系。【方法】体外循环心脏手术患者23例,测转流前、转流10min、转流末、转流后24h的血清S-100B蛋白表达水平。【结果】①血清S-100B蛋白质量浓度在体外循环前后动态变化:转流前(M)为0.27μg/L,转流10min后升至0.57μg/L(P<0.01),转流末达峰值1.80μg/L(P<0.01),转流后24h降为0.22μg/L(P>0.05)。转流末的血清S-100B蛋白质量浓度与转流时间呈正相关(r=0.488,P<0.05)。②停跳组(n=6)转流前、转流10min、转流末、转流后24h平均血清S-100B蛋白质量浓度分别为(0.17±0.09)μg/L、(0.48±0.13)μg/L、(1.65±0.52)μg/L和(0.19±0.04)μg/L,不停跳组(n=6)分别为(0.26±0.14)μg/L、(0.71±0.41)μg/L、(1.59±0.84)μg/L和(0.23±0.11)μg/L,两组差别无统计学意义(P>0.05)。【结论】体外循环可导致血清S-100B蛋白表达增高,其表达水平与心肺转流时间呈正相关,但与停跳或不停跳转流方式无关。     

Accentuated antagonism by angiotensin II on guinea-pig cardiac L-type Ca-currents enhanced by β-adrenergic stimulation

 To examine mechanism(s) underlying the accentuated antagonism by angiotensin II (A-II) on twitch tension, we recorded L-type Ca²⁺ currents (I _Ca,L) using conventional patch-clamp techniques in single, guinea-pig, ventricular myocytes. I _Ca,L was recorded by a step-pulse protocol after eliminating K⁺ conductances (internal Cs⁺ plus tetraethylammonium chloride and K⁺-free extracellular solution). A-II (100 nM) did not affect basal I _Ca,L, but inhibited I _Ca,L that had been enhanced (approximately 200% of control) by (ISO, isoproterenol 100 nM). The inhibitory action of A-II was concentration dependent (concentration eliciting 50% inhibition 88±9 pM, n=41) and the ISO-enhanced component of I _Ca,L was completely blocked by A-II at concentrations above 10 nM. CV-11974 (500 nM), an A-II type-1 receptor (AT₁) antagonist, prevented the inhibitory action of A-II. Pre-incubation with pertussis toxin (PTX) abolished the inhibitory effect of A-II. A-II also inhibited the I _Ca,L enhanced by histamine (500 nM) and forskolin (1 μM), but failed to affect I _Ca,L enhanced by intracellular cyclic adenosine monophosphate (1 mM). The inhibitory action of A-II may therefore involve AT₁ receptors/PTX-sensitive, guanine nucleotide-binding (G) proteins (Gi)/adenylate cyclase and partially explains the A-II-dependent accentuated antagonism of inotropy.     

内毒素休克大鼠核因子κB活化规律及其在生物蝶呤诱生中的作用

目的观察内毒素休克大鼠血浆及主要脏器核因子(NF)κB活化规律及其对生物蝶呤(BH4)和一氧化氮(NO)表达水平的影响,探讨内毒素休克时NF-κB信号通路对BH4诱生NO的分子调控机制及其与多器官功能损害的关系。方法将47只大鼠按表格随机法分为正常组(8只)、内毒素／脂多糖(LPS)组(24只,每观察时相点8只,均同时注射LPS制成休克模型)和拮抗组[15只,每观察时相点5只,均同时注射LPS并以吡咯烷二硫代氨基甲酸盐(PDTC)拮抗]。休克及拮抗组于注射LPS后2、6、12 h观察,并与正常组同法处死,无菌留取大鼠血标本及肝、肺、肾组织,测定组织中NF-κB活性和三磷酸鸟苷环水解酶Ⅰ(GTP-CHⅠ)和诱导型一氧化氮合酶(iNOS)mRNA表达水平、血浆和组织中的BH4含量及NO水平、肝脏和肾脏功能指标、肺组织髓过氧化物酶活性。结果与正常组(例如肺组织中NF-κB活性为26±6)比较,LPS组大鼠组织中NF-κB迅速活化(P<0．01),并于注射后2 h达峰值(肺组织中为291±44);LPS组各组织中GTP-CHⅠ和iNOS mRNA表达、BH4和NO水平也较正常组明显升高(P<0．05或0．01),至伤后12 h仍持续较高水平。此外,该组相应器官功能均受到不同程度的损害。应用PDTC的拮抗组大鼠各组织中NF-κB活性均较LPS组有所降低,GTP-CHⅠ、iNOS mRNA表达及BH4、NO水平显著受抑,肝、肺、肾功能明显改善。结论内毒素休克时机体内NF-κB通路高度活化,并对BH4／NO系统具有明显调节效应;可通过下调BH4介导的iNOS的过度活化抑制NF-κB信号途径,从而减轻组织炎性反应,对机体脏器功能起到保护作用。     

Die Insuffizienz der intraabdominellen Infektabwehr bei der eitrigen Peritonitis — Folge einer gestörten Fremdkörperopsonierung

Summary Despite a high concentration of serum proteins and intact phagocytes peritonitis exudates contain a large number of viable, pathogenic bacteria. The reason for this biological paradox is unknown. Our investigations reveal a pronounced defect in humoral opsonization of foreign particles in peritonitis exudate. We evaluated a modified chemiluminescence system allowing the determination of opsonic activity in serum and exudate. In serum we found a close correlation between opsonic activity and immunologically measurable levels of C₃-complement and IgG. In purulent peritonitis exudates, however, the actual opsonizing activity was much less than expected according to the opsonin concentrations. We found a pronounced difference between immunologically determined opsonin levels and impaired opsonic function. Employing crossed immunoelectrophoresis massive C₃-splitting into smaller fragments could be demonstrated in peritonitis exudates. In these exudates we found very high concentrations of granulocyte proteolytic (elastase) and oxidative (myeloperoxidase) enzymes which may lead to a functional destruction of opsonins followed by impaired opsonization in peritonitis exudate. The great number of bacteria and foreign particles in addition can cause a pronounced physiological consumption of complement components. The almost complete breakdown of intact C₃-complement in intraabdominal exudate explains the deficient host defence in patients with severe peritonitis.

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Abkürzungsverzeichnis CL Chemilumineszenz - IgG Immunglobulin G - OK Opsonierungskapazität