阿托伐他汀对冠状动脉微栓塞后心肌炎症的影响

目的 探讨阿托伐他汀干预治疗对冠状动脉微栓塞（CME）后心肌炎症的影响.方法 48只清洁级雄性SD大鼠经左心室内注射自体微血栓,同时短暂夹闭主动脉,建立大鼠CME模型后,随机分为未治疗组及阿托伐他汀（Atrovastatin）干预组,于术后7 d处死.HE染色观察梗死心肌,免疫组织化学染色及Western blot检测肿瘤坏死因子α（TNF-α）、白介素6（IL-6）及细胞间黏附因子1（ICAM-1）等炎症因子在心肌中表达的变化.结果 阿托伐他汀可轻度减少梗死面积,显著抑制CME后心肌中白细胞浸润及TNF-α、IL-6、ICAM-1 蛋白表达（P均〈0.05）.结论 阿托伐他汀能显著抑制CME后心肌炎症反应.     

The role of hypothalamic estrogen receptors in metabolic regulation

Estrogens regulate key features of metabolism, including food intake, body weight, energy expenditure, insulin sensitivity, leptin sensitivity, and body fat distribution. There are two ‘classical’ estrogen receptors (ERs): estrogen receptor alpha (ERS1) and estrogen receptor beta (ERS2). Human and murine data indicate ERS1 contributes to metabolic regulation more so than ESR2. For example, there are human inactivating mutations of ERS1 which recapitulate aspects of the metabolic syndrome in both men and women. Much of our understanding of the metabolic roles of ERS1 was initially uncovered in estrogen receptor α-null mice (ERS1^−/−); these mice display aspects of the metabolic syndrome, including increased body weight, increased visceral fat deposition and dysregulated glucose intolerance. Recent data further implicate ERS1 in specific tissues and neuronal populations as being critical for regulating food intake, energy expenditure, body fat distribution and adipose tissue function. This review will focus predominantly on the role of hypothalamic ERs and their critical role in regulating all aspects of energy homeostasis and metabolism.     

rhIL一1α与1，25一（OH）2D3联合作用对人牙周膜成纤维细胞表达RANKL和OPG的影响

目的：研究rhIL-1α与1,25-（OH）2D3联合作用对HPDLFs表达RANKL和OPG的影响,探讨牙槽骨改建的调节机制。方法：10μg/L rhIL-1α与1×10-8 mol/L1,25-（OH）2D3联合作用于体外培养的HPDLFs,于48h后收集细胞,利用荧光定量RT-PCR技术检测RANKL mRNA和OPG mRNA的表达,探讨RANKL/OPG比值的变化。结果：rhIL-1α和1,25-（OH）2D3都调节HPDLFs表达RANKL和OPG。rhIL-1α单独作用上调HPDLFs表达RANKL和OPG,增加RANKL/OPG比值（P〈0.05）;1,25-（OH）2D3单独作用则上调表达RANKL,下调表达OPG,增加RANKL/OPG比值（P〈0.05）。这2种调节因子联合作用对HPDLFs RANKL表达有协同作用,但对RANKL/OPG比值的影响无协同效应。结论：rhIL-1α和1,25-（OH）2D3都通过RANKL-OPG途径调节HPDLFs参与牙槽骨改建,2种调节因子联合作用对RANKL表达的影响明显优于单因素诱导效果,但对RANKL/OPG比值的影响并没有产生协同效应或累加效应。     

Early pregnancy induced expression of prostaglandin E2 receptors EP2 and EP4 in the ovine endometrium and regulated by interferon tau through multiple cell signaling pathways

Prostaglandin E2 (PGE₂) plays pleiotropic roles at fetal-maternal interface during establishment of pregnancy. The objectives of the study were to: (i) determine regulation of PGE2 receptors EP1, EP2, EP3, and EP4 in the endometrium during the estrous cycle and early pregnancy; and (ii) understand endometrial epithelial and stromal cell-specific hormonal regulation of EP2 and EP4 in sheep. Results indicate that: (i) early pregnancy induces expression of EP2 and EP4 but not EP1 and EP3 proteins in the endometrium on days 12-16 compared to that of estrous cycle; (ii) intrauterine infusion of interferon tau (IFNT) increases expression of EP2 and EP4 proteins in endometrium; and (iii) IFNT activates distinct epithelial and stromal cell-specific JAK, EGFR, ERK1/2, AKT, or JNK signaling module to regulate expression of EP2 and EP4 proteins in the ovine endometrium. Our results indicate a role for EP2 and EP4-mediated PGE₂ signaling in endometrial functions and establishment of pregnancy in ruminants.     

Certolizumab pegol: a new biologic targeting rheumatoid arthritis

The past decade has been an exciting period for clinical research and patient care in rheumatoid arthritis. This is mostly due to targeted biologic agents that have changed the outcome of this disease. Certolizumab pegol (Cimzia^®, UCB Inc., GA, USA), which targets TNF-α with a different mechanism of action than widely used biologics, was initially investigated for Crohn’s disease but has now been shown to be effective for rheumatoid arthritis. There have been three significant clinical trials demonstrating the efficacy of certolizumab pegol in active rheumatoid arthritis; two with combination methotrexate and one with monotherapy. This article will summarize the data from those trials and compare some of the characteristics of certolizumab pegol to conventional disease-modifying antirheumatic drugs and other biologic agents. Treatment recommendations are beyond the scope of this review; however, with many options available, there will be annotations on current trends in the care of this chronic disease.     

肿瘤坏死因子-α抗体对梗阻性黄疸大鼠肾脏IP3R表达的影响

目的研究肿瘤坏死因子-α(TNF-α)单克隆抗体对梗阻性黄疸大鼠肾功能的影响及机制。方法将60只雄性SD大鼠随机分成假手术组、模型组、干预组,采用胆总管结扎(CBDL)造梗黄模型,干预组于结扎后第2周开始腹腔注射TNF-α单克隆抗体[0.1 mg/(kg.2d)]。并于干预后1、2、3、4周麻醉动物,假手术组与5周模型组动物同批麻醉,留取肝和肾组织。采用HE染色确定模型建立情况,通过Western blot方法检测1,4,5-三磷酸肌醇受体(IP3R)的含量,免疫组织化学方法检测IP3R在肾组织的表达。结果 HE染色显示模型组和干预组肾间质有炎性细胞浸润,干预组较轻。免疫组化和Western blot显示模型组肾组织IP3R蛋白表达较多,干预组略下降,但均明显高于假手术组(P<0.05)。结论梗阻性黄疸时肾小球前小动脉平滑肌细胞内的IP3R蛋白的表达增强,而TNF-α单克隆抗体干预治疗可减轻IP3R表达增强的程度,部分减轻肾功能损害的发生。     

内毒素刺激诱导人外周血细胞促炎细胞因子的释放

目的：探讨内毒素（LPS）体外刺激对人外周血细胞高迁移率族蛋白B1（HMGB1）及肿瘤坏死因子（TNF）-α、白介素（IL）-6和IL-10分泌的影响.方法：采集20例健康志愿者外周血,与培养基等体积混合后体外培养,给予不同浓度LPS（100 ng/ml,500 ng/ml）刺激,分别于刺激后0、2、6、12、24 h收集细胞培养上清液,ELISA法检测其HMGB1和TNF-α、IL-6、IL-10的含量.结果：体外LPS刺激诱导外周血细胞分泌HMGB1增加,12 h后表达持续升高（P〈0.01）,分泌水平呈明显时间依赖性;TNF-α、IL-6产生亦呈时间、剂量依赖性,分别于24 h和6～12 h达分泌高峰（P〈0.01）;IL-10表达量均较低.结论：TNF-α、IL-6为早期炎症介质,HMGB1为介导内毒素所致迟发死亡的重要晚期炎症介质,它们在脓毒症的发生、发展中可能扮演重要角色.     

蛋白激酶Cα相互作用蛋白在瑞芬太尼痛觉过敏中的作用

背景 瑞芬太尼痛觉过敏是指应用瑞芬太尼所导致的机体对伤害性刺激的反应增强,其发生机制与N-甲基-D-天冬氨酸(N-methyl-D-aspartic acid,NMDA)受体-蛋白激酶C (protein kmase C,PKC)通路介导的脊髓中枢敏化相关.蛋白激酶Cα相互作用蛋白(protein interacting withCαkinase,PICK1)是PKCα的靶蛋白之一,也是在PKCα和突触后膜受体蛋白间起重要作用的衔接蛋白. 目的 探讨PICK1在瑞芬太尼痛觉过敏发生及维持中的作用. 内容 对PICK1的结构、功能及其在瑞芬太尼痛觉过敏中的研究进行综述. 趋向 通过PICK1在瑞芬太尼痛觉过敏中的研究,为瑞芬太尼痛觉过敏的预防及治疗提供新的靶点.