急性脑梗死患者血清sFas和sFasL水平的观察研究

目的 通过检测急性脑梗死(acute cerebral infarction,ACI)患者血清可溶性Fas(soluble Fas,sFas)和可溶性Fas配体(soluble Fasligand,sFasL)表达水平的变化,探讨sFas和sFasL与ACI病情变化的关系.方法 60例ACI患者(男性32例,女性28例)为研究组,30例健康体检者(男性12例,女性18例)为对照组.用酶联免疫吸附法检测两组血清sFas和sFasL水平,比较两组之间sFas和sFasL浓度的差异.结果 ACI组48 h、7 d和14 d时血清sFas水平分别为(6.27±1.48)ng/L、(4.99±1.15)ng/L和(3.74±0.58)ng/L,均显著高于对照组的(3.00±0.38)ng/L(F=7.29,P<0.01);ACI组48 h、7 d和14 d时血清sFasL水平分别为(4.40±1.32)ng/L、(3.19±0.94)ng/L和(1.91±0.45)ng/L,均显著高于对照组的(1.15±0.21)ng/L(F=8.60,P<0.01).大梗死组sFas和sFasL水平分别为(7.63±0.64)ng/L和(5.01±1.16)ng/L,显著高于小梗死组的(4.98±0.91)ng/L(t=12.12,P<0.01)和(3.58±0.87)ng/L(t=5.35,P<0.01).ACI患者血清sFas和sFasL水平呈正相关性(r=0.748,P=0.01).结论 血清sFas和sFasL水平高提示ACI患者梗死体积较大.     

急性心肌梗死患者合并2型糖尿病时脑钠肽及Fas系统的变化

目的观察急性心肌梗死（AMI）患者伴有2型糖尿病（T2DM）时血清脑钠肽（BNP）及Fas凋亡系统的变化。方法将AMI患者67例,分为T2DM组（32例）和非T2DM组（35例）,收集患者一般临床资料,采用免疫荧光法测定发病24h和7d时的BNP,采用ELISA法测定sFas、sFasL浓度。结果T2DM组24h和7d时BNP均高于非T2DM组（P均〈0．05）。T2DM组sFas及sFasL浓度在24h时升高,7d时下降,但均较非T2DM组高（P均〈0．05）。结论合并T2DM的AMI患者BNP的变化可早于心功能的改变,糖尿病能增高Fas细胞凋亡系统水平,加速心肌细胞凋亡。     

原发性胆汁肝硬化患者血清可溶性Fas、FasL水平变化及意义

采用双抗体夹心酶联免疫吸附法法检测20例原发性胆汁性肝硬化患者(PBC组)和24例正常体检者(对照组)血清可溶性Fas、FasL、(sFas、sFasL)水平.结果与对照组比较,PBC组血清sFas水平明显升高(P＜0.05),sFasL水平无明显差异(P＞0.05).提示检测血清sFas水平有助于PBC的诊断.     

心力衰竭患者血浆sFas 和sFasL水平的变化及其意义

目的:探讨凋亡相关因子可溶性Fas(sFas)及其可溶性Fas配体(sFasL)在心力衰竭(HF)患者血浆中的水平及其意义。方法:采用酶联免疫吸附法(ELISA)测定HF组(67例)和对照组(20例)患者血浆中sFas和sFasL的水平。结果:HF组血浆sFas水平均高于对照组,sFasL水平在心功能Ⅲ～Ⅳ级时高于对照组,并随心功能状况的下降而增加,与心功能有良好的相关性(P<0.01),其水平与原发病无关。结论:HF患者血浆中的sFas和sFasL水平显著升高,提示sFas和sFasL水平升高以至整个Fas/APO系统可能在HF的发病中起着重要作用。     

糖尿病对急性心肌梗死患者细胞凋亡因子和炎性因子的影响

目的了解糖尿病（DM）对急性心肌梗死（AMI）患者Fas受体细胞凋亡途径和炎症反应的影响。方法70例急性ST段抬高心肌梗死患者,根据是否合并DM分为非糖尿病（NDM）组（36例）和DM组（34例）。应用ELISA方法测定两组患者血清sFas、sFasL和TNF-α、IL-6的含量。结果AMI合并DM组直接PCI后血清sFas和sFasL浓度明显高于NDM组（4.18±0.86vs3.30±0.82μg/L,6.15±1.56vs4.34±1.37μg/L;P〈0.01）。前者血清TNF-α、IL-6的浓度也高于后者（32.78±6.16vs20.54±9.17ng/L,75.28±19.60vs54.35±14.74ng/L;t=2.476,2.598;P〈0.05）。心功能killip3、4级患者血清sFas、sFasL、TNF-α和IL-6的浓度均高于killip2、1级患者（F=4.52,P〈0.05）。结论糖尿病可能通过促进Fas/FasL系统的激活加速AMI时细胞凋亡的发生,同时加剧机体炎症反应,这可能是合并DM的AMI患者病情较重和预后不良的原因之一。     

高剂量极化液对心肌梗死患者细胞凋亡因子的影响

目的探讨急性心肌梗死(AMI)再灌注治疗联合高剂量极化液(GIK)持续静脉滴注对心肌损伤和细胞凋亡因子sFas和sFasL血清水平的影响。方法74例AMI患者再灌注后随机分为GIK组(35例)和非GIK组(39例),另设正常对照组(34例)。GIK组在接受再灌注后即刻予以高剂量GIK滴注24h。检测患者入组即刻、24h、3d、7d和14d血清sFas和sFasL水平。结果(1)AMI患者入组即刻血清sFas和sFasL水平明显高于正常对照组(P<0.01);(2)再灌注后GIK组和非GIK组血清sFas水平在24h显著降低(P<0.01),3～7d再次增高(P<0.01);(3)最为重要的发现是在14d时,sFas水平在GIK组明显降低(P<0.01),而非GIK组14d与7d比较差异无统计学意义;(4)血清sFasL水平在14d期间GIK组与非GIK组比较差异无统计学意义(P>0.05)。结论再灌注治疗联合高剂量GIK滴注明显降低AMI患者血清sFas水平,提示高剂量GIK可能通过减少缺血再灌注损伤实现对缺血心肌的保护作用。     

哮喘患儿血清sFas、sFasL、Eotaxin的变化及其意义

目的探讨血清可溶性Fas受体(sFas)及其配体(sFasL)、嗜酸性粒细胞趋化因子(Eotaxin)在哮喘患儿中的变化及其临床意义。方法选取确诊哮喘急性发作期患儿90例(急性期组)、选取同期哮喘缓解期患儿90例(缓解期组)、健康儿童90例(对照组),采用ELISA法检测三组血清sFas、sFasL、Eotaxin水平并进行比较,并分析不同病情的急性发作期患儿血清sFas、sFasL、Eotaxin水平及与血清总IgE(sIgE)的相关性。结果急性发作期组患儿的血清sFas、sFasL、Eotaxin、sIgE水平显著的高于缓解期组和对照组(P 0. 05),缓解期组患儿的血清sFas、sFasL、Eotaxin、sIgE水平显著的高于对照组(P 0. 05);重度组、中度组急性发作期组患儿的血清sFas、sFasL、Eotaxin水平显著的高于轻度组患儿(P 0. 05),重度组患儿的血清sFas、sFasL、Eotaxin水平显著的高于中度组(P 0. 05);重度组患儿的s IgE显著的高于轻度组(P 0. 05);急性发作期哮喘患儿血清sFas、sFasL、Eotaxin水平与血清sIgE呈显著的正相关关系(P 0. 05)。结论哮喘患儿血清sFas、sFasL、Eotaxin水平显著的升高,并且与病情、发作情况有关。     

糖尿病合并阿尔茨海默病患者血清可溶性凋亡相关因子及其配体的表达及临床意义

目的 探讨糖尿病合并阿尔茨海默病(AD)患者血清可溶性凋亡相关因子(sFas)和sFasL配体(sFasL)表达及临床意义。方法 选取2020年5月至2021年12月鄂州市中心医院老年病科老年2型糖尿病(T2DM)患者130例，根据是否合并AD分为合并组65例和未合并组65例，另选取同期单纯AD患者65例作为单纯AD组，老年健康体检者65例为对照组。检测各组血清sFas、sFasL水平。结果 合并组血清sFas、sFasL水平高于单纯AD组、未合并组及对照组，单纯AD组血清sFas、sFasL水平高于未合并组及对照组，未合并组血清sFas、sFasL水平高于对照组(P<0.05);合并组痴呆重度患者血清sFas、sFasL水平高于中度患者及轻度患者，中度患者血清sFas、sFasL水平高于轻度患者(P<0.05);血清sFas、sFasL水平与T2DM患者临床痴呆评定量表评分呈正相关(r=0.773、r=0.689,P<0.01);血清sFas、sFasL联合检测诊断T2DM合并AD的ROC曲线下面积(AUC)为0.836(95%CI:0.761～0.895),明显高...     

原发性肝癌双灌注介入治疗前后血清TNF-α和sFas水平的改变及意义探讨

目的了解原发性肝癌双灌注介入前后血清TNF-α、血清可溶性Fas（sFas）水平的变化,并探讨其临床意义。方法本研究选取75例原发性肝癌患者,其中30例行TACE治疗,45例行TACE联合脾动脉化疗药物灌注治疗,每个病例分别在术前一天、术后二周测定血清TNF-α、sFas,同时对所有病例进行近期疗效判定,另设30例正常对照组。结果肝癌患者的血清TNF-α和sFas的水平均明显高于正常对照组（P〈0.01）,TACE和双灌注治疗后血清TNF-α和sFas的水平均明显低于治疗前（P〈0.01）,双灌注治疗组治疗后血清TNF-α和sFas的水平分别低于TACE组治疗后水平（P〈0.05）,在双灌注组中,近期疗效达有效者血清TNF-α和sFas的水平明显低于无效者（P〈0.01）。结论原发性肝癌的双灌注介入治疗后血清TNF-α和sFas的水平明显降低,检测血清TNF-α和sFas的水平可以有助于预后估计。     

sFas,sFasL在乳腺癌中的表达及临床意义

目的探讨乳腺癌患者血清可溶性Fas(sFas)、可溶性FasL(sFasL)水平的变化及临床意义。方法采用ELISA法检测85例乳腺癌患者,24例乳腺良性病变者,30例为非乳腺疾病患者血清中sFas、sFasL的含量,分析两者与乳腺癌临床病理参数相关性及临床治疗对他们的影响。利用免疫组化S-P法检测85例乳腺癌及30例正常乳腺组织sFas和sFasL表达。结果乳腺癌患者血清sFas、sFasl水平高于两对照组,Ⅲ Ⅳ期高于Ⅰ Ⅱ期,治疗后低于治疗前(均P<0.05),sFas、sFasL与其他临床病理参数无显著相关性,两对照组血清sFas、sFasL水平无显著性差异(P>0.05)。正常乳腺上皮、原位癌、浸润性癌中表达阳性率分别为40.0%,52.9%,69.2%;0.0%,100.0%,100.0%。结论sFas、sFasL可能与乳腺癌的免疫逃逸有关,可作为乳腺癌新的肿瘤标志物。     

Influence of levothyroxine treatment on serum levels of soluble Fas (CD95) and Fas Ligand (CD95L) in chronic autoimmune hypothyroidism

Fas/FasL-mediated apoptosis results in the destruction of thyrocytes in chronic autoimmune hypothyroidism (CAIH). In this study, we examined the serum levels of soluble Fas (sFas) and soluble sFas ligand (sFasL) in euthyroid patients with chronic autoimmune hypothyroidism, who were taking levothyroxine (euthyroid, LT4-CAIH), to investigate the possible role of thyroid hormone therapy in down-regulation of apoptotic factors. Fifty euthyroid patients with CAIH on levothyroxine (median of duration 36 months, range 6-228 months) were compared with 75 age- and sex-matched healthy individuals. Serum levels of soluble Fas and soluble Fas Ligand, autoantibodies to thyroid peroxide and thyroglobulin were measured using ELISA. Serum levels of sFas were significantly higher in the euthyroid, LT4-CAIH group [median 9.12 ng/ml, interquartile range (7.86-10.72 ng/ml)] than in the controls [6.11 ng/ml (5.60-6.81 ng/ml)] (P < 0.0001). Compared with controls [80.33 pg/ml (68.22-103.70 pg/ml)], the euthyroid, LT4-CAIH group [125.71 pg/ml (106.11-149.48 pg/ml)] had significantly higher levels of sFasL (P < 0.0001). In a chronological study, there was no significant correlation between sFas, sFasL, and the duration of levothyroxine therapy. In conclusion, normalization of serum sFas and sFasL levels cannot be achieved during levothyroxine treatment in patients with CAIH. It appears that levothyroxine therapy has no important effect on down-regulation of apoptotic factors in CAIH. Thus, like thyroid autoantibodies, monitoring of serum levels of sFas/sFasL is not indicated during thyroid hormone therapy.     

Increased levels of soluble Fas in serum from diabetic patients with neuropathy.

OBJECTIVE: The aim of this study was to investigate circulating soluble Fas (sFas) and Fas ligand (sFasL), two transmembrane glycoproteins involved in apoptosis, in the serum of diabetic patients.MATERIAL AND METHODS: We assessed sFas and sFasL serum levels in normal controls (n=15), and in both 42 diabetic patients without complications, or with predominant retinopathy or neuropathy, using sFas and sFasL specific ELISA method.RESULTS: sFasL serum levels were less than 0.1 ng/ml in normal controls and in each group of diabetic patients. In diabetic patients with a predominant neuropathy, sFas serum levels were significantly increased not only when compared with normal controls (13.5 +/- 3.6 ng/ml vs 7.1 +/- 1.1 ng/ml, p<0.001), but also when compared with patients without complications (vs 9.1 +/- 1.8 ng/ml, p<0.001) or with a predominant retinopathy (vs 8.7 +/- 1.9 ng/ml, p<0.001).CONCLUSIONS: These preliminary data suggest that a dysregulation of the Fas system in peripheral neuronal cells may be involved in the increase of sFas observed in diabetic patients with neuropathy.     

Circulating soluble Fas ligand correlates with disease activity in Graves' hyperthyroidism

Apoptosis of thyrocytes may play an important role in the pathogenesis of autoimmune thyroiditis. Meanwhile, the Fas/Fas ligand (FasL) apoptosis pathway has received much attention in physiological homeostasis and immune regulation in various thyroid diseases, including Graves' hyperthyroidism (GD). FasL is a type II membrane protein of the tumor necrosis factor family, and induces apoptosis when it binds to Fas. Soluble FasL (sFasL) may also exert cytotoxic activity against Fas-expressing cells by producing trimerization of Fas molecule, but soluble Fas (sFas) is an apoptotic inhibitor. To determine the role of circulating sFas/sFasL in modulating disease activity of GD, we examined the circulating levels of sFas/sFasL in GD patients with various levels of anti-thyrotropin-stimulating hormone (TSH) receptor antibodies (TRAb). Serum samples were obtained from 22 consecutive untreated hyperthyroid GD patients with higher TRAb level (63.8% +/- 12.5%, group I) and 22 treated euthyroid GD patients, who were in a state of disease remission, with lower TRAb level (7.9% +/-5.9%, group II). The levels of sFas were significantly higher in group I (1.56 +/- 0.26 ng/mL) than in group II (0.76 +/- 0.26 ng/mL, P <.01). The levels of sFasL were also significantly higher in group I patients (0.153 +/- 0.018 ng/mL) than in group II patients (0.126 +/- 0.012 ng/mL, P <.01). A significant correlation was found between sFasL levels and TRAb activity in all GD patients (r = 0.69, P <.01). Because changes in sFasL levels and TRAb levels occur in parallel, increased serum sFasL in patients with GD may contribute to homeostasis in the thyroid. Serum sFasL may be considered to be a candidate marker for evaluating disease aggression or regression in GD.     

Soluble form of Fas and Fas ligand in serum and bronchoalveolar lavage fluid of individuals infected with human T-lymphotropic virus type 1

Human T-lymphotropic virus type 1 (HTLV-1) carriers are known to develop pulmonary complications characterized by T-lymphocytic alveolitis. The aim of this study was to determine the profile and role of soluble Fas (sFas) and sFas ligand (sFasL) in the lung of asymptomatic HTLV-1 carriers. We measured sFas and sFasL levels in serum and bronchoalveolar lavage fluid (BALF) of 16 seropositive asymptomatic HTLV-1 carriers and 32 healthy subjects. The serum levels of both sFas and sFasL were significantly higher in HTLV-1 carriers than in the control. In BALF, the percentage of lymphocytes and CD4 positive T-cells, and the levels of sFasL were also significantly higher in asymptomatic carriers than the control, but there were no significant differences in sFas levels between the two groups. There was a significant correlation between BALF sFasL levels and serum sFasL levels and percentage of CD4 positive T-cells in BALF. Our results suggest that the increased levels of sFasL in the lung of asymptomatic HTLV-1 carriers are associated with accumulation of CD4 positive T-cells, and that resistance to apoptosis in HTLV-1 infected T-cells and overproduction of sFasL could contribute to T-lymphocytic alveolitis by down-regulating Fas-FasL mediated apoptosis.     

Increased circulating levels of soluble Fas ligand are correlated with disease activity in patients with fibrosing lung diseases

OBJECTIVE: The Fas-Fas ligand (FasL) pathway is one of the important apoptosis-signalling molecule systems. We previously determined that this pathway may be involved in the pathogenesis of fibrosing lung diseases. In the present study, we evaluated the clinical significance of the levels of soluble forms of Fas (sFas) and FasL (sFasL) in serum from patients with fibrosing lung diseases. METHODOLOGY: We measured sFas, sFasL, KL-6 (a measure of alveolar type II cell damage), surfactant protein D (SP-D), and surfactant protein A (SP-A) levels in serum from 35 patients with idiopathic pulmonary fibrosis (IPF), 17 patients with interstitial pneumonia associated with collagen vascular diseases (CVD-IP), and 13 normal healthy controls using enzyme-linked immunosorbent assays (ELISA). RESULTS: The serum levels of sFasL were significantly increased in patients with active IPF and CVD-IP, compared with those with inactive disease and controls. There was no significant difference in sFasL levels between patients with inactive disease and controls. Serum sFasL levels were significantly correlated with lactate dehydrogenase and KL-6 levels in IPF. The decrease in sFasL levels following corticosteroid therapy was not correlated with the clinical course of IPF. There was no significant difference in serum sFas levels between IPF or CVD-IP patients and controls. CONCLUSIONS: Although further studies need to be performed on a large number of patients with histologically proven IPF or CVD-IP, it would seem that serum sFasL levels may reflect the activity of IPF and CVD-IP.     

Circulating nuclear matrix protein in Graves' disease

The Fas/Fas ligand system induces apoptosis, while soluble Fas (sFas) blocks the system and soluble Fas ligand (sFasL) functions to induce apoptosis. The assay of nuclear matrix protein (NMP) released from dead or dying cells can be used to quantitate cell death. Therefore, we evaluated the relationship among serum levels of NMP, sFas, and sFasL in patients with Graves' disease. We measured serum levels of sFas, sFasL, NMP, thyroid hormones and TSH receptor antibody in 20 normal control subjects (5 men, 15 women; mean age, 44.3 years), 32 patients with untreated Graves' disease (4 men, 28 women; mean age, 44.1 years), and 10 patients with Graves' disease treated by methimazole (3 men, 7 women; mean age 39.2 years). Serum NMP was significantly lower (10.4 +/- 4.3 IU/ml, p < 0.02) in patients with untreated Graves' disease than in patients with treated Graves' disease (16.4 +/- 7.3 IU/ml) and control subjects (15.3 +/- 8.9 IU/ml). Serum sFas and sFasL were significantly higher in patients with untreated Graves' disease than in patients with treated Graves' disease and in control subjects. In the patient groups with Graves' disease, serum NMP was negatively correlated with sFas (r = -0.612, p < 0.001) and serum sFas was positively correlated with FT4 (r = 0.360, p < 0.05) and TRAb (r = 0.384, p < 0.05). Serum NMP was correlated with sFas. These results suggest that serum NMP is decreased in patients with untreated Graves' disease, and that cell death or apoptosis in patients with Graves' disease is affected by soluble Fas under the influence of thyroid function.     

sFas与sFasL在自身免疫疾病中的意义

目的　研究sFas与sFasL在系统性红斑狼疮 (SLE)等自身免疫疾病中的意义及抗单链DNA(ssDNA)抗体与sFas和sFasL介导凋亡的相关性。方法　采用夹心ELISA方法检测 31例SLE病人 ,32例类风湿关节炎 (RA)病人 ,2 0例 1型糖尿病 (IDDM )病人及 5例多发性硬化病 (MS)病人血清中sFas与sFasL含量及抗ssDNA抗体水平。结果　在SLE、RA、IDDM及MS患者血清中的sFas含量 (pg/ml)分别为 2 881± 16 5 3 ,988± 6 96 ,135 2± 413 ,15 40± 5 6 6 ,明显高于正常对照 (P <0 0 0 2 ) ,SLE病人sFas含量高于RA ,MS ,IDDM病人。SLE、RA患者血清sFasL含量 (pg/ml)分别为5 35± 431、12 38± 1184,明显高于正常对照 (P <0 0 2 ) ,MS、IDDM患者血清sFasL含量 (pg/ml)分别为 2 5 1± 140 ,2 11± 73 ,低于正常对照 (P >0 0 5 )。在SLE、RA病人中 ,高浓度sFasL者伴有高浓度sFas。在SLE病人中 ,所有抗ssDNA抗体阳性者均伴有高浓度sFas,所有抗sFas阴性者 ,ssDNA抗体也为阴性。结论　在SLE等疾病中sFas水平明显高于正常人 ,可作为疾病进展与治疗效果的判断指标。抗ssDNA抗体与sFas具有关联性。sFas与sFasL在疾病中的相互作用及动态变化有待进一步研究     

Serum levels of soluble molecules associated with evasion of immune surveillance: a study in biliary disease.

BACKGROUND: Biliary carcinoma cells produce the transmembrane proteins, Fas, FasL, and RCAS1. It has been demonstrated that the Fas/FasL and RCAS1 systems induce apoptosis of activated immune cells and that the soluble isoforms of these proteins (sFas, sFasL, and sRCAS1) also exhibit this function. METHODS: We measured serum levels of these soluble-types in patients with biliary disease by ELISA and investigated their clinical significance. RESULTS: In some cases of cholangitis and autoimmune biliary disease, serum sFasL values were over 0.1 ng/ml but the protein was undetectable in any patients with biliary carcinoma. sFas levels were significantly higher in the autoimmune disease (mean, 6.83 ng/ml) and cancer (mean, 6.42 ng/ml) groups than in the cholangitis group (mean, 4.23 ng/ml) and normal controls (mean, 2.93 ng/ml). However, the sFas values in malignancy did not correlate with the progression of clinical stage. The percentage positive for serum sRCAS1 was 9.7% in benign disease but was 63.4% in cancer. CONCLUSIONS: Our data suggest that serum sFasL in biliary disease may be derived predominantly from activated immune cells and not from cancer cells and that autoimmune biliary disease may be mediated by the Fas/FasL apoptotic system. sRCAS1 is highly tumor-specific and may be of value in the diagnosis of malignancy.