阿托伐他汀短期强化治疗对急性冠脉综合征患者血浆sOX40L及hs—CRP浓度的影响

目的研究阿托伐他汀短期强化治疗对急性冠脉综合征（acutecoronarysyndrome,ACS）患者血浆sOX40L及高敏C反应蛋白（high．sensitivety Creactiveprotein,hs．CRP）浓度的影响。方法114例ACS患者按数字表法随机分为阿托伐他汀20mg／d组、40mg／d组和对照组,每组各38例,治疗前及治疗7d后分别测定ACS患者血浆sOX40L,hs—CRP及血脂浓度并进行比较分析。结果治疗前各组sOX40L,hs．CRP及血脂浓度比较,差异均无统计学意义（P〉0．05）。治疗7d后阿托伐他汀20mg／d组和40mg／d组血浆sOX40L,hs．CRP浓度降低,与治疗前比较差异有统计学意义（P〈0．05）;与对照组治疗后比较,差异亦具有有统计学意义（P〈O．05）;40mg／d组治疗后血浆sOX40L,hs．CRP浓度低于20mg／d组,差异有统计学意义[sOX40L：（274．55±24．32）pg·L^-1vs（318．13±55．03）Pg·L^-1,P〈0．05;hs．CRP：（3．02±2．55）mg·L^-1vs（4．46±1．22）mg·L^-1,P〈0．05]。治疗前阿托伐他汀20mg／d组和40mg／d组数据合并后sOX40L与hs—CRP呈正相关（r=0．712,P〈O．01）;治疗后阿托伐他汀两组数据合后sOX40L与hs-CRP呈正相关（r=0．748,P〈O．01）。结论阿托伐他汀短期强化治疗显著降低ACS患者血浆sOX40L及hs—CRP浓度．具有明显抗炎作用。     

不同剂量阿托伐他汀对急性冠脉综合征患者血浆可溶性OX40配体水平的影响

目的探讨不同剂量阿托伐他汀对急性冠脉综合征(ACS)炎症指标可溶性OX40配体(sOX40L)及高敏C反应蛋白(hs-CRP)的影响。方法收集47例因ACS住院的患者,随机分为小剂量组(阿托伐他汀10 mg/d)25例和大剂量组(阿托伐他汀20 mg/d)22例,治疗4周,测定治疗前后血浆sOX40L及hs-CRP的浓度。结果小剂量组和大剂量组的sOX40L及hs-CRP的血浆基线水平分别为:(27.69±10.52)ng/L和(28.24±10.01)ng/L,(11.69±7.09)mg/L和(11.91±6.36)mg/L,均显著高于以往报道的正常人群。治疗4周后,小剂量组和大剂量组sOX40L均显著下降,分别为(21.99±8.12)ng/L(t=10.732,P0.01)和(17.51±4.84)ng/L(t=9.052,P0.01),下降幅度分别为20.6%和38.0%,差异有统计学意义(t=2.252,P0.05)。两组hs-CRP也显著下降,下降幅度分别为32.3%(t=5.496,P0.01)和55.8%(t=8.006,P0.01),两组间比较差异有统计学意义(t=2.702,P=0.01)。治疗前后sOX40L与hs-CRP均呈正相关性(R=0.765,P=0.00;R=0.742,P=0.00)。结论 ACS患者血浆sOX40L水平明显高于正常人群。他汀类药物治疗ACS患者可显著降低sOX40L,并且sOX40L降低与hs-CRP降低同步,呈剂量依赖性。sOX40L可能同hs-CRP一样,可作为他汀类药物抗炎作用的指标之一。     

不同剂量阿托伐他汀对急性冠脉综合征患者高敏C反应蛋白的影响

目的探讨急性冠脉综合征患者使用不同剂量阿托伐他汀治疗2周对血清高敏C反应蛋白浓度的影响。方法连续入选2009年11月至2011年9月番禺中心医院收治的冠状动脉粥样硬化性心脏病（冠心病）患者126例,按电脑随机数字表法分为两组,每组63例。均给予抗凝、抗血小板聚集、血管紧张素转换酶抑制剂、p受体阻断药、硝酸酯类等药物治疗。小剂量组在常规治疗基础上给予口服阿托伐他汀20mg／d：大剂量组在常规治疗基础上给予1：3服阿托伐他汀40mg／d。所有患者在治疗前、治疗2周后分别测定血脂和血清高敏c反应蛋白（high sensitivety C reactive protein, hs-CRP）浓度,并进行比较分析。结果两组在治疗2周之后的血清总胆固醇、三酰甘油、低密度脂蛋白胆固醇及hs．CRP浓度与治疗前比较．均明显降低．差异有统计学意义（P〈0．05）;并且大剂量组血清总胆固醇[（4．42±0．62）mmol／L孤（4．95±0．67）mmol／L,P〈0．01]、三酰甘油[（1．02±0．19）mmol／L诋（1．13±O．23）mmol／L,P〈0．01]、低密度脂蛋白胆固醇[（2．55±0．46）mmol／L／）S．（2．64±0．33）mmo｜／L,P〈0．01]及hs．CRP[（9．66±1．48）mg／L眠（10．59±3．32）mg／L,P〈O．01]浓度降低幅度更大,与小剂量组治疗后比较,差异有统计学意义。结论阿托伐他汀能明显抑制急性冠脉综合征的炎性反应．降低血清hs-CRP浓度,并且治疗效果随剂量的增加而增强。     

OX40L对非ST段抬高性急性冠状动脉综合征再缺血事件的预测

目的:探讨非ST段抬高性急性冠状动脉综合征(ACS)患者外周血淋巴细胞表达OX40L及血浆可溶性OX40L(sOX40L)水平与再发缺血事件的关系。方法:选取我院336例非ST段抬高性ACS住院患者,收集患者基线资料及180d内发生急性心肌梗死(AMI)及因ACS再住院情况,对患者入院时血淋巴细胞表达OX40L、血浆sOX40L水平、高敏C反应蛋白(hs-CRP)水平进行检测;分析OX40L在淋巴细胞上的表达、血浆OX40L水平与再发缺血事件的关系并与CRP及预后的关系相比较。结果:外周血淋巴细胞OX40L高表达水平者随访30d(P<0.05)、高hs-CRP水平者30d(P<0.05)再缺血事件发生率高,Kaplan-Meier生存分析显示,较高淋巴细胞OX40L表达对30d预后的预测作用与较低水平者差异有统计学意义,淋巴细胞OX40L表达较hs-CRP水平更能提示近期预后。Logistic回归分析显示:年龄(OR:2.37,95%CI 1.10～4.81,P<0.05)、血糖水平(OR:2.46,95%CI1.16～4.92,P<0.05)、淋巴细胞OX40L表达水平(OR:4.20,95%CI 2.41～7.09,P<0.05)、血清hs-CRP(3.46,95%CI 1.39～7.82,P<0.05)为随访30d内再缺血事件发生的独立预测因素。结论:ACS患者急性期淋巴细胞OX40L表达、血清sOX40L水平可预测近期再缺血事件。     

阿托伐他汀对急性冠脉综合征患者血脂及C反应蛋白的影响

目的:探索阿托伐他汀对急性冠脉综合征(ACS)患者高脂血症及C反应蛋白(CRP)的作用。方法:82例 ACS患者随机分为阿托伐他汀组和常规治疗组,分别在入院时、1周后及接受高脂餐负荷实验后检测CRP和血脂水平。结果:阿托伐他汀治疗组患者治疗后CRP及总胆固醇(TC)、低密度脂蛋白-胆固醇(LDL-C)水平显著降低 (P<0．01),餐后血浆TG、CRP较对照组显著降低(P<0．001,<0．01)。结论:短期阿托伐他汀治疗可有效降低 ACS患者血清中CRP、TG、LDL-C水平。     

OX40/OX40L与急性冠状动脉综合征

急性冠状动脉综合征为一类慢性炎症性疾病,T细胞的激活是急性冠状动脉综合征的形成和发展的重要因素.OX40/OX40L是机体炎症反应中一对重要的信号通路,它们相互作用能促进CD4 T细胞的活化、增殖、迁移,因此OX40/OX40L可能参与急性冠状动脉综合征的形成.     

不同剂量阿托伐他汀对急性冠脉综合征患者高敏C反应蛋白的影响

目的:探讨不同剂量阿托伐他汀干预治疗对急性冠脉综合征(ACS)患者血脂及血清高敏C反应蛋白(hsCRP)的影响.方法:128例ACS患者被随机分为阿托伐他汀大剂量组(40mg/d,64例)和阿托伐他汀常规剂量组(20mg/d,64例),分别在人院24 h内及服药后3、7 d测定两组患者血脂、hs-CRP水平,并进行比较...     

不同剂量瑞舒伐他汀短期干预对ACS患者血浆TM、hsCRP水平的影响(英文)

目的:探讨不同剂量瑞舒伐他汀短期干预对急性冠脉综合征(ACS)患者血浆血栓调节蛋白(TM)及高敏C反应蛋白(hsCRP)的影响。方法:选择ACS患者32例,随机均分为10mg瑞舒伐他汀组和20mg瑞舒伐他汀组,并选择非冠心病患者16例为正常对照组;采用酶联免疫吸附法定量测定两治疗组治疗前后及正常对照组入院时的TM及hsCRP水平,并观察两治疗组1个月内药物不良反应及心血管事件的发生率。结果:ACS患者治疗前血浆TM及hsCRP水平均明显高于正常对照组(P均<0.001);与治疗前比较,治疗7d后两组TM[10mg组:(54.09±52.45)μg/dl比(15.65±2.30)μg/dl,20mg组:(70.27±62.43)μg/dl比(19.86±5.49)μg/dl]及hsCRP[10mg组:(126.35±76.08)ng/ml比(54.85±45.30)ng/ml,20mg组:(125.35±60.29)ng/ml比(58.14±53.54)ng/ml]水平明显降低(P均<0.01);但两种治疗剂量对ACS患者血浆TM、hsCRP影响的差异无显著性(P均>0.05),且其随访期的药物不良反应发生率差异亦无显著性(P>0.05);瑞舒伐他汀20mg治疗组患者主要心血管事件发生率(MACE):再发心绞痛明显低于10mg组(18.75%比62.50%,P<0.01)。结论:早期强化他汀药物(20mg/d)治疗能降低ACS患者血浆血栓调节蛋白及高敏C反应蛋白水平,有效降低心血管事件的发生率,但不明显增加药物不良反应率。     

强化阿托伐他汀对急性冠脉综合征C反应蛋白及血脂的影响

目的:观察不同剂量阿托伐他汀(10mg/d和40mg/d)早期干预对急性冠脉综合征(ACS)患者C反应蛋白(CRP)、血总胆固醇(TC)、低密度脂蛋白-胆固醇(LDL-C)水平的影响,以了解较大剂量阿托伐他汀对ACS患者免疫炎症抑制的影响及安全性。方法:72例ACS患者被随机分为两组,A组在常规治疗基础上予阿托伐他汀10mg/d,睡前口服;B组在常规治疗基础上予阿托伐他汀40mg/d,睡前口服,均在入院48h内开始用药,治疗4周,分别予用治疗前、后监测血清CRP、血脂(TC、LDL-C)浓度,同时观察用药安全性。结果:治疗后两组患者血清CRP、血脂均有不同程度的下降(P0.05～0.01),与A组相比较,B组CRP[(16.45±6.45)mg/L:(11.48±6.83)mg/L]、TC[(5.38±0.64)mmol/L:(4.92±0.50)mmol/L]、LDL-C[(2.53±0.46)mmol/L:(1.95±0.39)mmol/L]下降更明显(P均0.05)。两组均无严重不良事件。结论:较大剂量阿托伐他汀早期干预治疗可显著降低急性冠脉综合征患者血清C反应蛋白浓度及血脂水平,并具有良好的安全性。。     

强化瑞舒伐他汀治疗对急性冠脉综合征患者PCI术后hsCRP的影响

目的:观察强化瑞舒伐他汀治疗对急性冠脉综合征患者经皮冠状动脉介入治疗(PCI)术后不同时间点高敏C反应蛋白(hsCRP)的影响。方法:选择2011年7月~2012年6月在我院诊断为急性冠脉综合征患者86例,随机分为2组。强化组于PCI术前服用瑞舒伐他汀20 mg/d,术后持续1周,1周后减量为10 mg/d。对照组PCI术前术后均为10 mg/d。分别于术前、术后1 d、术后1周,术后1个月检测患者血浆中hsCRP的变化。结果:强化组患者PCI术后1 d、术后1周血浆hsCRP的水平明显低于对照组,而PCI术后1个月两组患者血浆hsCRP的水平无显著差异。结论:PCI术前及术后1周应用瑞舒伐他汀20 mg/d较10 mg/d能够明显降低血浆hsCRP水平,且安全性良好。     

OX40/OX40L分子在炎症性肠病免疫病理机制中的作用

OX40/OX40L是一对重要的协同刺激分子,它们能增强CD 4~ T细胞的扩增、成熟和产生效应功能,还可使T细胞免于凋亡,并促进记忆性T细胞产生。因此,OX40/OX40L在机体的免疫应答和多种疾病中起重要作用。目前的研究表明免疫异常是炎症性肠病发病的重要因素,此文就OX40/OX40L的生物学功能及其在IBD中的作用作一综述。     

The upregulated expression of OX40/OX40L and their promotion of T cells proliferation in the murine model of asthma

Objective

To investigate whether the expression of OX40/OX40 ligand (OX40L) was upregulated in a murine model of asthma and their significance in the pathogenesis of asthma.

Methods

After an ovalbumin-sensitized/challenged murine model of asthma was established, the expressions of OX40, OX40L in peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage fluid (BALF) cell pellets were measured. Then T cell proliferation was analyzed by cell counting kit-8 (CCK8), and the protein levels of OX40 and OX40L in the lungs were determined by immunohistochemistry. The concentrations of IL-4 and IFN-γ in BALF and T cell culture supernatant were evaluated by ELISA.

Results

The percentages of CD4⁺OX40⁺, CD19⁺OX40L⁺, F4/80⁺OX40L⁺ in PBMCs and BALF cell pellets were higher in asthma group than in control group (all P<0.01). The proliferation capacity of T cells in asthma group was higher than that in control group (P<0.05). In asthma group, stimulation of OX40 by anti-OX40 mAb obviously promoted T cell proliferation and secretion of IL-4 and IFN-γ. Immunohistochemistry assay showed that OX40 and OX40L protein levels were higher in asthma group than those in control group (all P<0.05).

Conclusions

The expressions of OX40 and OX40L were upregulated in the murine asthmatic model. The upregulation of OX40/OX40L signals could induce the proliferation and cytokines secretion of T cells in asthmatic mice, indicating that OX40/OX40L signal was involved in the pathogenesis of asthma.     

Retroviral transduction of acute myeloid leukaemia-derived dendritic cells with OX40 ligand augments their antigen presenting activity

Recent studies have shown that human myeloid leukaemia cells can differentiate into dendritic cell (DC)-like cells (leukaemia-DCs) when cultured with a combination of cytokines. In the present study, we examined whether the transduction of leukaemia-DCs with OX40 ligand (OX40L), a member of the tumour necrosis factor (TNF) family, resulted in augmentation of their antigen presenting activity. Bicistronic retroviral vectors expressing both human OX40L and enhanced green fluorescent protein (EGFP) or EGFP alone were generated and used for transduction. Fresh leukaemic cells from five patients with acute myeloid leukaemia (AML) were isolated and retrovirally transduced with OX40L during the culture with a combination of cytokines from stem cell factor, fms-like tyrosine kinase (Flt)-3 ligand, granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-4 (IL-4) and TNF-alpha. After 7 d, the majority of cells showed DC-like morphology, and expressed higher levels of CD80, CD86 and HLA-DR than fresh leukaemic cells. The transduction efficiency was 8.5-27.2%. Leukaemia-DCs transduced with OX40L elicited higher proliferative response of allogeneic CD4+ T cells than fresh leukaemic cells, non-transduced, or mock-transduced leukaemia-DCs. Co-culture of allogeneic CD4+ T cells with OX40L-transduced leukaemia-DCs was superior in the generation of interferon (IFN)-gamma producing CD4+ T cells and in production of IFN-gamma. Furthermore, OX40L-transduced leukaemia-DCs could elicit significant proliferative response of human leucocyte antigen-matched T cells from the donor in allogeneic stem cell transplantation. These results indicate that retroviral transduction of leukaemia-DCs with OX40L augments their antigen presenting cell activity and thus renders them more suitable for tumour vaccines or ex vivo stimulation of leukaemia-specific T cells.     

Roles of OX40 in the Pathogenesis and the Control of Diseases

OX40 belongs to the tumor necrosis factor receptor superfamily, and its expression is restricted to activated T-cells. Ligation of OX40 during T-cell-dendritic cell interaction is crucial for clonal expansion of antigen-specific T-cells and generation of T-cell memory. The ligand of OX40 (OX40L) is expressed not only on dendritic cells but also on other cell types, such as B-cells, vascular endothelial cells, natural killer cells, and mast cells. The pathophysiological relevance of this broad distribution needs further investigation. In particular, OX40L on vascular endothelial cells may play a role in inflammatory vasculitis as well as in atherosclerotic change. Recent studies with animal models have indicated the critical involvement of OX40 in the pathogenesis of a variety of immunologic abnormalities of inflammatory, autoimmune, infectious, allergic, and allotransplantation-related diseases. Blockade of OX40-OX40L interaction has been shown to prevent, cure, or ameliorate these diseases. In contrast, activation of OX40 is known to break an existing state of tolerance in malignancies, leading to a reactivation of antitumor immunity. These findings clearly suggest that the OX40/OX40L system is one of the most promising targets of immune intervention for treatment of these diseases.     

○X40L在慢性丙型肝炎患者外周血单核细胞表达水平变化的临床意义

目的 研究慢性丙型肝炎(chronic hepatitis C,CHC)患者的OX40L分子表达特点及其临床意义.方法 采用流式细胞仪对35例CHC患者和30例健康对照者外周血单核细胞表面OX40L的表达情况进行了调查,并进一步分析了OX40L表达水平与患者临床指标的关系.结果 与健康对照者相比,CHC患者外周血单核细...     

阿托伐他汀对不稳定型心绞痛患者高敏C反应蛋白的影响

目的研究不同剂量的阿托伐他汀对不稳定型心绞痛患者血清高敏C反应蛋白水平的影响。方法选取我院不稳定型心绞痛患者51例,随机分为小剂量组28例和大剂量组23例,分别给予阿托伐他汀10mg或40mg,每日1次。共用药30日,治疗前后分别测定患者血脂水平和血清高敏C反应蛋白水平。结果阿托伐他汀用药30日后,两组血脂水平和血清高敏C反应蛋白水平均明显降低,低剂量组从(17±6)μg/L降至(8.3±2.7)μg/L;高剂量组从(18±7)μg/L降至(8±3)μg/L。两组下降程度比较,差异有统计学意义。结论早期应用阿托伐他汀治疗不稳定型心绞痛,可减少斑块基质成分的降解和炎症反应,具有稳定斑块作用,使用大剂量阿托伐他汀的获益更多。     

OX40-OX40L轴对动脉粥样硬化小鼠淋巴细胞活性氧和亲环素A表达的调控作用

目的　探讨OX40-OX40L相互作用对C57BL/6J小鼠活性氧（ROS）水平及亲环素A（CyPA）表达的影响。　方法　采用C57BL/6J小鼠颈动脉硅胶圈置入法快速建立动脉粥样硬化斑块模型,免疫组织化学法检测颈动脉粥样硬化（As）斑块内CyPA的表达;小鼠淋巴细胞表达CyPA采用Western　Blot检测;采用流式细胞术检测CD4、OX40及细胞内ROS水平。　结果　C57BL/6J小鼠形成As斑块后,淋巴细胞表达OX40较非As小鼠明显增加,同时发现As小鼠淋巴细胞内ROS水平和CyPA表达水平显著增加;体外应用anti-OX40特异性刺激OX40-OX40L轴后,淋巴细胞表达OX40及ROS水平显著上调,anti-OX40L特异性阻断OX40-OX40L后,淋巴细胞OX40表达减少,细胞分泌ROS水平较刺激组降低（P<0.05）;体外培养淋巴细胞6　h,刺激组分泌的CyPA水平明显高于抑制组（P<0.001）。　结论　OX40-OX40L相互作用能调控动脉粥样硬化小鼠活性氧水平及亲环素A表达。     

高敏C反应蛋白在急性冠状动脉综合征中临床意义的研究

目的探讨高敏C反应蛋白(hsCRP)与急性冠状动脉综合征(ACS)病变程度的关系及临床意义。方法测定经冠状动脉造影证实为ACS患者(n=54)的血清hsCRP浓度,与正常对照组(n=18)的hsCRP浓度相比较,分析二组间及ACS组中,冠状动脉病变支数与相应hsCRP浓度的关系。结果hsCRP浓度在对照组,不稳定型心绞痛组,急性心肌梗死组依次增高,分别为(1.474±1.063)mg/L,(5.753±4.168)mg/L,(12.140±6.679)mg/L。在ACS组中,单支病变组,双支病变组,三支病变组,其hsCRP浓度也依次增高,分别为(5.513±2.458)mg/L,(8.321±4.785)mg/L,(12.423±4.104)mg/L。结论hsCRP可作为ACS患者判断病情严重程度及预后的指标。