大鼠脑出血后血肿周围组织和血浆S-100B蛋白的表达

目的:研究大鼠脑出血后血肿周围组织和血浆中S100B蛋白的变化。方法:用Ⅶ型胶原酶立体定位法制作大鼠尾状核脑出血模型,采用免疫组织化学染色法和酶联免疫吸附法观察脑出血血肿周围组织和血浆中S100B蛋白在出血后不同时间点表达的变化。结果:脑出血早期,血肿周围组织S100B反应阳性细胞明显增加,血清S100B浓度明显增高,1～3d达峰值。脑出血后4hS100B表达最强,阳性细胞体积增大,突起增粗、增长,阳性细胞数量较多,一直持续至出血后3d。结论:脑出血后血肿周围组织S100B表达与神经胶质细胞坏死有关,并可通过受损血脑屏障进入血液,S100B可作为脑损伤早期的外周标记物。     

高血压脑出血病人血清S100B蛋白和神经元特异性烯醇化酶的变化及意义

目的 探讨高血压脑出血病人血清S100B蛋白和神经元特异性烯醇化酶（NSE）浓度变化及其与出血量、脑组织损伤情况及预后之间的关系.方法 高血压脑出血病人52例,对照组30例.测定脑出血病人起病第1、3、7天血清S100B蛋白和NSE浓度,分析浓度的变化与出血量、格拉斯哥预后评分（GOS）之间的关系.结果 脑出血组血清S100B蛋白和NSE浓度明显高于对照组（P＜0.001）,与出血量呈正相关（P＜0.05）,其浓度的变化与预后有关.结论 高血压脑出血病人血清S100B蛋白和NSE浓度变化能在一定程度上反映出血量的大小、脑组织损伤的情况,有助于评估病人预后.     

急性脑梗死患者血清S100蛋白B及胶质纤维酸性蛋白的变化及其临床意义

目的 研究S100蛋白B(S100B)、胶质纤维酸性蛋白(GFAP)在急性脑梗死患者不同病程时期的水平变化规律,分析其在疾病发生发展中的临床意义.方法 检测急性发病不超过24小时的脑梗死患者不同时期血清中S100B、GFAP的水平变化,结合神经功能缺失程度,并通过前后自身对照,分析S100B、GFAP在疾病发生发展中的意义.结果 急性缺血性脑梗死患者血清中S100B、GFAP明显高于对照组.最初24小时内S100B的水平与第3～5天、7～10天神经功能缺失程度显著相关.结论 S100B水平与神经功能缺失程度相关,其在发病后24小时内的血清浓度可提示之后的神经功能缺损.S100B可作为监测急性脑梗死预后的标记物.     

中药治疗对不同出血量脑出血大鼠模型血清S100蛋白水平的影响

目的:探寻中医药治疗脑出血的最佳出血量.方法:老龄Wistar大鼠136只,随机分为假手术组、模型组及治疗组,模型组及治疗组按不同出血量各分为4组.造模后,假手术组、模型组给予安慰剂,治疗组给予中药治疗.给药3d、5d后,采用酶联免疫法测定大鼠腹主动脉血清S100浓度.结果:治疗组血清S100水平明显低于模型组(P＜0.05),小出血量组(27.40μl)血清S100水平明显低于大出血量组(53.67μl)(P＜0.05).结论:中药治疗对脑出血后脑组织S100蛋白水平有明显影响,可以保护脑组织的损伤,对少量脑出血作用更加明显.     

中药对不同出血量脑出血模型大鼠血清S100蛋白水平的调控

目的 探讨中医药治疗脑出血最佳疗效出血量的界定.方法 72只老年Wistar大鼠随机分为假手术组、模型组和给药组,模型组和给药组又根据不同出血量分组.造模后,假手术组和模型组给予安慰剂,给药组给予中药治疗.给药3 d后腹主动脉取血采用酶联免疫法测定血清S100浓度.结果 给药组血清S100水平明显低于模型组(P＜0.05),小量出血组(27, 40 μl)血清S100水平明显低于大量出血组(53, 67 μl)(P＜0.05).结论 中药对脑出血后血清S100水平的调控有明显效果,可以保护脑组织的损伤,对小量脑出血作用更加明显.     

桑葚提取物对脂多糖诱导的心肌细胞炎症反应和细胞凋亡的影响

目的探讨桑葚提取物(ME)对脂多糖(LPS)致心肌细胞炎症反应和细胞凋亡的影响及分子机制。方法以正常培养的H9c2细胞作为对照组;用10 mg/L LPS处理的H9c2细胞作为LPS组;分别用50、100、200 mg/L的ME处理H9c2细胞,再用10 mg/L LPS处理,作为ME低、中、高浓度组。将si-NC、si-S100B转染至H9c2细胞中,再用10 mg/L LPS处理,作为LPS+si-NC组、LPS+si-S100B组;将pcDNA、pcDNA-S100B转染至H9c2细胞中,用200 mg/L ME处理,再用10 mg/L LPS处理,作为LPS+ME+pcDNA组、LPS+ME+pcDNA-S100B组。酶联免疫吸附法检测肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)水平;流式细胞术检测心肌细胞凋亡;Western blot检测Bcl-2、Bax、S100钙结合蛋白B(S100B)的蛋白表达;实时荧光定量PCR检测S100B mRNA表达水平。结果不同浓度ME处理的心肌细胞中TNF-α、IL-6的分泌水平降低,细胞凋亡率显著降低,Bcl-2表达水平显著升高,Bax和S100B表达水平均显著降低,且呈浓度依赖性。干扰S100B表达能抑制LPS诱导的心肌细胞炎症反应和细胞凋亡,S100B过表达则逆转了ME对LPS诱导的心肌细胞炎症反应和细胞凋亡的抑制作用。结论ME可抑制LPS诱导的心肌细胞炎症反应和细胞凋亡,其机制可能与下调S100B有关。     

S100B蛋白与中枢神经系统损伤

S100B蛋白对中枢神经系统(CNS)损伤的敏感性较高,能用于多种形式和不同程度CNS损伤的临床和预后判断,甚至可用于脑死亡的判断.测定S100B蛋白预测继发性脑损伤,使医生选择适当的时机开始治疗干预将是未来研究的热点.S100B蛋白是一种很有临床应用前景的生物蛋白标志物.     

结核分枝杆菌通过诱导宿主产生S100A8/A9促进T细胞死亡的机制研究北大核心CSCD

目的探讨结核分枝杆菌(Mtb)诱导宿主产生的S100钙结合蛋白A8/A9复合物(S100A8/A9)促进T细胞死亡的作用及机制。方法灭活毒性Mtb H37Rv(iMtb H37Rv)与野生型(WT)小鼠全脾细胞体外共同培养不同时间,通过流式细胞术得到S100A8与S100A9的表达差异以及产生S100A8/A9的细胞群。Mtb H37Rv体外诱导WT和S100a9^(-/-)小鼠全脾细胞,通过流式细胞术检测S100A8/A9对CD4^(+)T细胞死亡的影响。采用不同浓度S100A8/A9与人T淋巴细胞系Jurkat细胞共同培养、S100A8/A9与细胞共培养不同时间或是S100A8、S100A9单体以及S100A8/A9复合物与细胞共同培养,通过流式细胞术得到S100A8/A9对Jurkat细胞死亡的影响。通过Western blot检测不同细胞表面TLR4的表达差异。封闭Jurkat细胞表面TLR4受体后与S100A8/A9共同培养,通过流式细胞术得到Jurkat细胞死亡的变化。结果与对照组相比,iMtb H37Rv能诱导脾细胞产生更多的S100A8和S100A9蛋白。S100A8/A9能促进小鼠CD4^(+)T细胞死亡。低剂量的S100A8/A9复合物能诱导Jurkat细胞死亡,且S100A8和S100A A9单体无以上作用。S100A8/A9复合物诱导T细胞死亡为TLR4非依赖通路。结论Mtb通过诱导宿主产生S100A8/A9并促进T细胞死亡。     

老年脑出血患者血清神经元特异性烯醇化酶、S100β蛋白与认知功能障碍的相关性

目的探讨老年脑出血患者血清神经元特异性烯醇化酶(NSE)、S100β蛋白水平与认知功能障碍和预后的相关性。方法选择急性自发性非外伤性脑出血老年患者100例,另选择同期健康体检者100例作为对照组,脑出血患者均于入院时给予手术治疗,进行血清NSE与S100β蛋白表达检测,采用美国国立卫生研究院卒中量表(NIHSS)评分、欧洲脑卒中量表(ESS)以及日常生活能力Barthel指数(BI)进行评定。分析浓度的变化与出血量、神经功能缺损情况、日常生活以及认知功能障碍的关系。结果脑出血组患者治疗前血清NSE、S100β蛋白水平明显高于对照组(P0.05);脑出血组患者治疗7 d后NSE、S100β蛋白水平均明显下降,但仍高于对照组(P0.05);脑出血组患者出血量、NIHSS评分、认知功能障碍与血清NSE、S100β蛋白浓度呈正相关。结论 NSE和S100β蛋白水平与神经功能缺损及脑卒中后认知功能障碍有密切的关系,可用于判断脑出血患者神经功能缺损及认知功能障碍的严重程度。     

S100B与急性缺血性脑损伤

S100B是一类酸性钙结合蛋白,在中枢神经系统中主要存在于胶质细胞,是星形胶质细胞活化的标志之一.S100B可反映胶质细胞的功能,调节神经元与胶质细胞之间复杂的相互作用.近年来的研究显示,S100B蛋白参与了急性缺血性脑损伤的病理学过程,血清S100B蛋白可作为预测脑梗死严重程度、进展以及转归的标记物.

Abstract：

S100B is a class of acid calcium-binding protein. It mainly exists in neuroglial cells in the central nervous system, and it is one of the signs of astrocyte activation. S100B may reflect the function of neuroglial cells and regulate the complex interactions between the neurons and neuroglial cells. Studies in recent years have demonstrated that S100B protein is involved in the pathological processes of acute ischemic brain injury. Serum S100B protein can be used as an important marker for identifying the severity of cerebral infarction, progress and outcome.     

Type 1 diabetes promotes disruption of advanced atherosclerotic lesions in LDL receptor-deficient mice

Cardiovascular disease, largely because of disruption of atherosclerotic lesions, accounts for the majority of deaths in people with type 1 diabetes. Recent mouse models have provided insights into the accelerated atherosclerotic lesion initiation in diabetes, but it is unknown whether diabetes directly worsens more clinically relevant advanced lesions. We therefore used an LDL receptor-deficient mouse model, in which type 1 diabetes can be induced at will, to investigate the effects of diabetes on preexisting lesions. Advanced lesions were induced by feeding mice a high-fat diet for 16 weeks before induction of diabetes. Diabetes, independently of lesion size, increased intraplaque hemorrhage and plaque disruption in the brachiocephalic artery of mice fed low-fat or high-fat diets for an additional 14 weeks. Hyperglycemia was not sufficient to induce plaque disruption. Furthermore, diabetes resulted in increased accumulation of monocytic cells positive for S100A9, a proinflammatory biomarker for cardiovascular events, and for a macrophage marker protein, without increasing lesion macrophage content. S100A9 immunoreactivity correlated with intraplaque hemorrhage. Aggressive lowering primarily of triglyceride-rich lipoproteins prevented both plaque disruption and the increased S100A9 in diabetic atherosclerotic lesions. Conversely, oleate promoted macrophage differentiation into an S100A9-positive population in vitro, thereby mimicking the effects of diabetes. Thus, diabetes increases plaque disruption, independently of effects on plaque initiation, through a mechanism that requires triglyceride-rich lipoproteins and is associated with an increased accumulation of S100A9-positive monocytic cells. These findings indicate an important link between diabetes, plaque disruption, and the innate immune system.     

S100A8/A9 aggravates post-ischemic heart failure through activation of RAGE-dependent NF-κB signaling

The extracellular heterodimeric protein S100A8/A9 activates the innate immune system through activation of the receptor of advanced glycation end products (RAGE) and Toll-like receptors. As activation of RAGE has recently been associated with sustained myocardial inflammation and heart failure (HF) we studied the role of S100A8/A9 in the development of post-ischemic HF. Hypoxia led to sustained induction of S100A8/A9 accompanied by increased nuclear factor (NF-)κB binding activity and increased expression of pro-inflammatory cytokines in cardiac fibroblasts and macrophages. Knockdown of either S100A8/A9 or RAGE rescued the induction of pro-inflammatory cytokines and NF-κB activation after hypoxia. In a murine model of post-ischemic HF both cardiac RNA and protein levels of S100A8/A9 were elevated as soon as 30 min after hypoxia with sustained activation up to 28 days after ischemic injury. Treatment with recombinant S100A8/A9 resulted in reduced cardiac performance following ischemia/reperfusion. Chimera experiments after bone marrow transplantation demonstrated the importance of RAGE expression on immune cells for their recruitment to the injured myocardium aggravating post-ischemic heart failure. Signaling studies in isolated ventricles indicated that MAP kinases JNK, ERK1/2 as well as NF-κB mediate signals downstream of S100A8/A9-RAGE in post-ischemic heart failure. Interestingly, cardiac performance was not affected by administration of S100A8/A9 in RAGE^?/?-mice, which demonstrated significantly improved cardiac recovery compared to WT-mice. Our study provides evidence that sustained activation of S100A8/A9 critically contributes to the development of post-ischemic HF driving the progressive course of HF through activation of RAGE.     

Neuron-Specific Enolase,S100 Calcium-Binding Protein B,and Heat Shock Protein 70 Levels in Patients With Intracranial Hemorrhage

The authors evaluated neuron-specific enolase (NSE), S100 calcium-binding protein B (S100B), and heat shock protein 70 (HSP 70) levels and their relationships with in-hospital mortality, Glasgow Coma Scale (GCS) scores, and National Institute of Health Stroke Scale (NIHSS) scores.In total, 35 patients older than 18 years were presented to our emergency department and were diagnosed with non-traumatic intracranial hemorrhage (ICH) and 32 healthy controls were included. Blood samples were drawn on days 0 and 5.S100 calcium-binding protein B and HSP levels were significantly higher in patients than in controls on days 0 and 5. Neuron-specific enolase levels were higher in patients than in controls on day 0, but there was no significant difference on day 5.S100 calcium-binding protein B was negatively correlated with GCS, whereas it was positively correlated with NIHSS and bleeding volume. There was also a negative correlation between NSE and GCS, but it was not statistically significant. In addition, no significant correlation was found in terms of bleeding volume or NIHSS. Heat shock protein 70 was negatively correlated with GCS and positively correlated with bleeding volume and NIHSS, but these results were not statistically significant. S100 calcium-binding protein B and HSP 70 levels were significantly higher in those who died compared with survivors. The areas under the curve of S100 B, NSE, and HSP 70 for mortality were 0.635, 0.477, and 0.770, respectively.Neuron-specific enolase, S100B, and HSP 70 levels are simple, inexpensive, and objective measures in cases of ICH. These tests can be used to support an assessment for screening ICH patients with clinical scoring systems, such as GCS and NIHSS.     

Argon plasma coagulation versus injection sclerotherapy in peptic ulcer hemorrhage--a prospective, controlled study

BACKGROUND/AIMS: In Slovenia, the annual incidence of peptic ulcer hemorrhage is 118/100,000 inhabitants, with mortality up to 14%. Interventional endoscopy has largely reduced mortality in these patients. This study aims to evaluate the efficacy and safety of argon plasma coagulation and injection sclerotherapy in bleeding peptic ulcer. METHODOLOGY: A prospective, controlled study which includes 100 patients with peptic ulcer hemorrhage (male 63, female 37, av.age 57.1 years, SD+/-16, span 26-80; gastric ulcer 50 patients, duodenal ulcer 50 patients) in the period between 1.01.1999 and 15.05.2000 treated in our institution. The bleeding activity was determined according to the Forrest classification. Fifty patients were randomized to receive argon plasma coagulation (ARCO 2000 ES unit, group A) and in fifty patients injection sclerotherapy (sclerosing with diluted adrenalin 1:10,000 plus polidocanol 1%, group B) was performed. The groups did not differ with respect to age, sex, site, severity of bleeding, use of NSAID and additional diseases. RESULTS: Clinically and endoscopically diagnosed rebleeding occured in 7/50 patients (14%) in group A and in 9/50 patients (18%) in group B; p=0.78. The majority of rebleeding occured within 48 hours after endoscopic hemostasis, group A 4-/7 (57.1%), group B 7/9 (77.7%), p = 0.74. Repeated endoscopic hemostasis did not prove successful in 8 patients (group A 3/50, 6%, group B 5/50, 10%), p=0.71. Seven patients were treated operatively. The total mortality rate was 9% (9/100 patients, group A 4/50, 8%, group B 5/50, 10%), p>0.05. Only one patient died due to peptic ulcer hemorrhage, other 8 patients died due to concomitant diseases. CONCLUSIONS: Argon plasma coagulation seems to be an effective and safe alternative to other hemostatic modalities in peptic ulcer hemorrhage.     

Influences of traumatic brain injury on the outcomes of delayed and repeated hemorrhages.

Effects of traumatic brain injury (fluid percussion) on outcomes of hemorrhage, either delayed (70.5 min after the injury) or repeated (0.5 min after injury, then followed by a delayed hemorrhage), were examined in 4 groups of 10 anesthetized rats. Comparisons were made for delayed hemorrhage following sham injury (A1) vs. injury (A2) and for repeated hemorrhage following sham injury (B1) vs. injury (B2). No significant differences were observed in MAP, Cl, HR, SVI, SVRI, and CVP between groups A1 and A2. Hemodynamic recovery was significantly better in B1 than B2 at 70 min after the initial hemorrhage. The respective values of MAP and Cl for the groups B1 and B2 at 70 min were 65 +/- 3 vs. 56 +/- 4 mmHg and 220 +/- 15 vs. 182 +/- 15 ml/min/kg. Brain trauma did not affect survival rate (90 vs. 100%) following delayed hemorrhage, but significantly worsened the outcome of repeated hemorrhage. The 130 min survival rates for groups B1 and B2 were 50% and 10% (P = 0.08), respectively; their survival curves were significantly different (P = 0.02). Our data indicate that brain trauma has greater impact on responses to immediate hemorrhage than delayed hemorrhage, suggesting that traumatic brain injury may have a time-dependent effect on the response to hemorrhage.     

Proteins of the S100 family regulate the oligomerization of p53 tumor suppressor

S100B protein is elevated in the brains of patients with early stages of Alzheimer's disease and Down's syndrome. S100A4 is correlated with the development of metastasis. Both proteins bind to p53 tumor suppressor. We found that both S100B and S100A4 bind to the tetramerization domain of p53 (residues 325-355) only when exposed in lower oligomerization states and so they disrupt the tetramerization of p53. In addition, S100B binds to the negative regulatory and nuclear localization domains, which results in a very tight binding to p53 protein sequences that exposed the tetramerization domain in their C terminus. Because the trafficking of p53 depends on its oligomerization state, we suggest that S100B and S100A4 could regulate the subcellular localization of p53. But, the differences in the way these proteins bind to p53 could result in S100B and S1004 having different effects on p53 function in cell-cycle control.     

Serum S100B levels in patients with cerebral and extracerebral infectious disease

S100B has been shown to increase in cerebrospinal fluid (CSF) and serum after various neurological diseases and it has been postulated that S100B could serve as a serum marker for brain damage. However there is limited information concerning serum S100B levels in infectious diseases of the brain. Blood samples were collected from patients at the Department of Infectious Diseases at or soon after admission. The different diagnoses studied were bacterial meningitis, pneumonia, viral meningitis, cerebral abscess, enteritis, erysipelas, viral encephalitis and neuroborreliosis. A serum S100B level > 0.15 microg/l was defined as increased. 57 patients were included in the study. S100B was elevated in 33% of patients (19/57). 73% (8/11) of patients with bacterial meningitis showed increased levels compared to 7% (1/14) of patients with viral meningitis. Viral encephalitis showed the highest mean S100B levels (mean 0.58 microg/l). 25% (6/24) of patients with extracerebral infections showed raised S100B levels. S100B levels were generally higher in patients with cerebral infections than in extracerebral infections. However, both false negative and false positive S100B levels were observed which may limit the use of S100B as a brain specific serum marker.     

Raised serum S100B protein levels in neuropsychiatric lupus

OBJECTIVE: To test serum S100B protein levels in patients with and without neuropsychiatric systemic lupus erythematosus (NPSLE) and controls. METHODS: 87 patients with SLE, 23 with and 64 without neuropsychiatric involvement, and 25 control subjects were prospectively evaluated. NPSLE diagnosis was made according to the American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Serum S100B protein levels were determined with a luminescence immunoassay. Statistical analysis was performed using Mann-Whitney and Kruskal-Wallis tests. RESULTS: Among the patients with NPSLE, 9 presented psychosis; 4, cranial neuropathy; 3, cerebrovascular disease; 1, seizures; 1, chorea; 1, peripheral polyneuropathy; 1, multiplex mononeuropathy; 3, dementia. Serum concentrations of S100B protein were significantly higher in patients with NPSLE (median 0.164 ng/ml, interquartile range 0.113-0.332) than in non-NPSLE patients (0.062 ng/ml, 0.026-0.109) and controls (0.088 ng/ml, 0.013-0.124) (p<0.001). Patients with anti-dsDNA antibodies had higher S100B protein levels (p = 0.001). No significant associations were found of lupus activity (among non-NPSLE cases), antiphospholipid antibodies, and reduced complement levels with S100B concentration. CONCLUSIONS: Serum S100B protein level is raised in NPSLE, reflecting continuing neurological damage. The association of anti-dsDNA antibodies with higher S100B protein concentration deserves further study.