细菌脂多糖对氯丙嗪肝毒性作用的影响

目的 确定吩噻嗪类抗精神病药氯丙嗪（CPZ）的肝毒性的特征与表现，并通过低剂量脂多糖（LPS）诱导炎症对此种肝毒物肝毒性的影响来研究短期炎症与药物肝毒性之间的关系，以枯否氏细胞（KC）特异性抑制剂氯化钆（GdCl3）为工具药，研究肝脏炎症介质在CPZ的肝毒性以及在LPS对药物肝毒性的调节效应中所发挥的作用，探讨其施加影响所发生机制、过程、环节及途径。     

原发性高血压醛固酮合成酶与肥胖及炎症因子关系研究进展

原发性高血压（EH）是最常见心血管疾病,65％-75％高血压患者伴肥胖。高血压伴肥胖日益威胁着人类健康。肾素（PRA）-血管紧张索（hng）-醛固酮（ALD）系统（RAAS）激活、水钠潴留、交感神经系统功能亢进、内皮功能异常、慢性低度炎症等危险因素,最终导致血压升高。     

酒精性肝病的治疗

酒精性肝病（Alcoholic liver disease．ALD）是由于长期大量饮酒所致的肝脏损伤．其发病率在我国呈逐年上升趋势。ALD的发生与氧化应激反应、细胞因子（TNF—α，TGF—β等）产生异常、免疫异常、蛋氨酸代谢异常、铁超负荷、酒精代谢相关酶类基因多态性等多种因素有关。在临床上有酒精性脂肪肝（AFL），酒精性肝炎（AH），酒精性肝纤维化（AF），酒精性肝硬化（AC）以及轻症酒精性肝病（AML）等不同的阶段。ALD的治疗．虽然在不同的阶段不尽相同，但总的治疗原则大致相似，其重点在于恢复酒精及其代谢产物造成的肝脏病理损伤和代谢紊乱．避免及逆转肝纤维化的发生。     

乙醇乙醛脱氢酶基因多态性与乙醇性肝病关系的实验研究

乙醇性肝病（ALD）是由于长期大量饮酒引起的肝脏病变。ALD的发病机制学说众多，但其确切机制至今尚不十分清楚。有关孪生子患乙醇性肝硬化的发生率的研究中发现，单卵双胞胎与双卵双胞胎相比有较高的发生率，提示个体间遗传差异是过度饮酒者对乙醇性肝病易感性的基础。对个体遗传素质的研究主要集中在乙醇脱氢酶（ADH）和乙醛脱氢酶（ALDH）基因多态性方面。目前，国内关于ADH和ALDH基因多态性与ALD关系的研究报道不多。     

肝肠轴相关机制研究进展

1998年马歇尔提出了“肠-肝轴”的概念,从此肝脏疾病的发生与肠黏膜屏障的作用就逐渐受到关注。目前的研究认为,如果肠道黏膜屏障功能受损,致使肠道黏膜的通透性发生改变,从而导致肠道内的细菌及其产物（如内毒素等）,通过血液循环（通常是门静脉系统）进入肝脏,引起肝脏固有免疫系统如Kupffer细胞（kupffer cell,KC）等被肠道产物激活,释放一系列炎性因子,这些炎性因子可进一步造成肠道黏膜及远隔器官损伤。因此,保护肠黏膜屏障可能是治疗肝脏疾病的开创性治疗方法和辅助治疗方法。进一步认识肝肠轴相互作用的机制可为临床上治疗肝脏疾病提供新的思路。本文就肝肠轴的相关机制及研究该机制的重要性作一综述。     

rrhaIlion／LFB签订合作开发和商品化Shigamabs的意向书

Alder公司与BMS公司达成一项许可证贸易协议。按照协议BMS公司将获得开发和商业化前者的先导化合物ALD518用于所有潜在适应症（癌除外）的世界范围独家权利。ALD518是一种人源化单克隆抗体，被设计用于阻滞趋炎分子白介素-6（IL-6），后者在与类风湿关节炎（RA）有关的炎症级联中起关键作用。同时，它也被研究用于癌治疗和癌支持治疗。     

酒精性肝硬化中西医治疗现状及进展

酒精性肝病（ALD）是由于长期大量饮酒所致的慢性肝脏疾病,其分五类：轻症酒精性肝病（AML）、酒精性脂肪肝（AFL）、酒精性肝炎（AH）、酒精性肝纤维化（AF）、酒精性肝硬化（AC）。在这里我们着重探讨一下酒精性肝硬化的研究现状及中西医治疗进展。     

五灵胶囊中部分化学成分对脂多糖诱导枯否细胞释放炎症因子的影响

目的观察五灵胶囊（Wuling capsules,WL）中部分化学成分对脂多糖（lipopolysaccharider,LPS）诱导大鼠原代枯否细胞（Kupffer cell,KC）表达ERK（extracellular signal-regulated kinase）和核因子（nuclear factor-kappa B,NF-κB）调节炎症因子和介质的作用。方法分离大鼠KC,采用60μg L 1 LPS诱导KC分泌炎症因子及NOS,ELISA测定TNF-α、IL-6、IL-8,比色法测定NOS,Western blot检测全蛋白ERK、p-ERK、NF-κBp50、NF-κBp65、p-NF-κBp65、p-IκK、p-IκB及核、浆蛋白NF-κBp65、p-NF-κBp65的变化。结果 WL明显下调LPS活化KC表达p-ERK、p-NF-κBp65、p-IκK、p-IκB蛋白,模拟WL混合成分（Mix）及6单体成分明显下调LPS活化KC表达p-ERK和p-NF-κBp65信号通路蛋白。各受试药物组均能降低核内p-NF-κBp65表达,减少p-NF-κBp65入核抑制炎性基因转录,降低活化KC过量分泌TNF-α、IL-6、IL-8和NOS。结论 WL中五味子醇甲、五味子乙素、隐丹参酮、丹参酮ⅡA、柴胡皂苷D是干预LPS诱导KC表达ERK、NF-κB信号通路蛋白,抑制炎性因子与介质基因转录而减少TNF-α、IL-6、IL-8和NOS分泌的有效成分。     

酒精性肝病与自噬的研究进展

酒精性肝病(ALD)是引起慢性肝脏疾病的主要原因之一,其发病机制复杂,自噬与肝脏疾病的研究日益深入,如何认识自噬在ALD发生发展过程中扮演的角色,旨在为ALD防治提供新途径。     

还原型谷胱甘肽对大鼠酒精性肝损伤的保护作用

在我国由于饮酒导致酒精性肝病（ALD）的发生率呈明显上升趋势。本研究通过建立大鼠酒精性肝病模型，探讨还原型谷胱甘肽对ALD的治疗作用。 1 材料与方法     

病毒性肝炎发病的免疫学机制与抗肝炎新药研究的思考

免疫反应在病毒导致的肝损伤和自身免疫性肝炎的发病机制中起着重要的作用。无效的免疫反应不仅不能清除病毒 ,相反导致肝细胞的持续损伤。肝损伤的免疫学机制涉及到多种细胞 ,包括淋巴细胞、单核巨噬细胞 (Kupffer细胞 )、肝内皮细胞、肝实质细胞和星状细胞。淋巴细胞的激活是免疫介导肝损伤的起始步骤。激活的淋巴细胞通过死亡配体和受体的结合诱导肝细胞的凋亡。淋巴细胞进一步激活巨噬细胞 ,导致多种炎症细胞因子的释放 ,继而导致细胞死亡级联反应 ,介导肝损伤。对肝细胞免疫损伤机制的探讨为研制防治肝病的药物提供了新的思路     

3, 5, 3′-Triiodothyroacetic acid (TRIAC) is an anti-inflammatory drug that targets toll-like receptor 2

Drug repositioning is a strategy that explores new pharmaceutical applications of previously launched or failed drugs, and is advantageous since it saves capital and time. In this study, we examined the inhibition of TLR2 signaling by drug candidates. HEK-Blue?-hTLR2 cells were pretreated with drugs and stimulated using the TLR2 ligand, Pam3CSK4. Among the drugs that inhibited TLR2 signaling, we selected TRIAC, which is yet to be patented. Pretreatment with TRIAC decreased the TLR2 level and the phosphorylation of Akt and MAPKs in HEK-Blue?-hTLR2 cells. Since TLR2 is overexpressed in patients with acute hepatitis, we confirmed that TRIAC alleviates necrosis in a mouse model of Con A-induced acute hepatitis. The serum AST and ALT levels are indicators of liver damage, and are increased in Con A-induced hepatitis. Additionally, TLR2 and inflammatory cytokine levels are increased following administration of Con A and lead to liver damage. TRIAC decreased the serum levels of AST and ALT, and reduced liver tissue necrosis in mice with Con A-induced acute fulminant liver damage, by reducing the levels of inflammatory cytokines. In conclusion, TRIAC alleviates inflammation in mouse models of Con A-induced hepatitis by inhibiting the phosphorylation of Akt and MAPKs, the sub-mechanisms underlying TLR2 signaling.     

The effects of cytokines on the atherosclerotic process

Atherosclerotic lesions result from a series of highly specific cellular and molecular responses to various endogenous risk factors and potential exogenous antigens. The cellular mechanisms involved in atherogenesis, with the exception of calcification and thrombotic events, are principally no different to those found in chronic inflammatory fibroproliferative diseases such as liver cirrhosis, rheumatoid arthritis, glomerulosclerosis, pulmonary fibrosis or chronic pancreatitis. These responses are mediated by interactions among endothelial cells, monocyte-derived macrophages, smooth muscle cells and specific subtypes of T lymphocytes. Monocyte and lymphocyte activation leads to the release of a wide spectrum of cytokines and chemokines that have key roles in all of the phases of endothelial damage, as well as in the formation and rupture of the atherosclerotic plaques. This review attempts to analyze the role of chemokines and cytokines in the multiple steps of atherosclerotic process.     

丹参酮ⅡA对LPS等诱导的肝细胞损伤及枯否细胞释放细胞因子的作用

目的研究丹参酮ⅡA(TSHⅡA)对枯否细胞(kupffercell,KC)释放细胞因子致肝细胞损伤的影响,以探讨丹参治疗慢性肝病的机制。方法分离肝细胞和KC并建立DGlaN、LPS损伤肝细胞模型,测定培养上清中ALT、MAO、LDHL、GSHST、MDA,LPS作用KC释放细胞因子同时放免法测定TNFα、IL6、IL8,HE染色观察细胞形态,免疫组化法观察TNFα、CD14、iNOS、eNOS在细胞内表达,双层小室培养观察LPS刺激KC释放细胞因子对肝细胞的损伤。结果TShⅡA能修复DGlaN和LPS诱导损伤的肝细胞,反映肝细胞损伤的酶水平和MDA明显低于DGlaN和LPS组,能明显抑制LPS诱导KC分泌TNFα、IL8,100ng·L-1升高IL6作用。TShⅡA尚能抑制KC表达TNFα、CD14、iNOS、eNOS,并有效地抑制KC释放过量的细胞因子损伤肝细胞,但对细胞因子所致肝细胞损伤无直接保护作用。结论TShⅡA抑制DGlaN、LPS损伤肝细胞作用机制与有效抑制KC释放过量的细胞因子参与肝损伤有关。     

Role of inflammation in the mechanism of acetaminophen-induced hepatotoxicity

Acetaminophen (AAP) overdose and the resulting hepatotoxicity is an important clinical problem. In addition, AAP is widely used as a prototype hepatotoxin to study mechanisms of chemical-induced cell injury and to test the hepatoprotective potential of new drugs and herbal medicines. Because of its importance, the mechanisms of AAP-induced liver cell injury have been extensively investigated and controversially discussed for > 30 years. This review highlights recent new insight into intracellular events critical for liver cell death. In addition, the relevance of the inflammatory response is addressed, including cytotoxic and inflammatory mediators generated by activated inflammatory cells, that is, resident macrophages and lymphocytes as well as newly recruited blood-derived leukocytes. Inflammation is a critical component of the overall pathophysiology, not only as a potential factor that may aggravate cell damage, but more importantly as a vital response to limit cell injury, remove cell debris and promote regeneration.     

蜂毒肽在治疗炎性疾病中的研究进展

炎性疾病是指因过度炎症反应所引发的或伴有炎症并发症的一类可影响人类健康的病症。目前临床上可通过抑制炎症反应达到治疗炎性疾病的目的,而常用的抗炎药虽然疗效明确,但都存在明显的不良反应,易给机体造成二次伤害,故抗炎新药亟待开发。蜂毒肽是从蜂毒中分离出的主要有效成分,具有较强的抗炎活性,其可通过介导炎症通路信号传递、抑制炎症细胞活性及炎症介质分泌等途径治疗多种炎性疾病,且疗效较好,具有较为广阔的临床应用前景。本文主要对蜂毒肽在治疗不同炎性疾病中的作用特点、蜂毒肽主要不良反应及应对策略进行了总结,以为后期蜂毒肽抗炎应用的临床开发提供参考。     

Complement C3a binding to its receptor as a negative modulator of Th2 response in liver injury in trichloroethylene-sensitized mice

Trichloroethylene (TCE) is a major occupational health hazard and causes occupational medicamentosa-like dermatitis (OMLDT) and liver damage. Recent evidence suggests immune response as a distinct mode of action for TCE-induced liver damage. This study aimed to explore the role of the key complement activation product C3a and its receptor C3aR in TCE-induced immune liver injury. A mouse model of skin sensitization was induced by TCE in the presence and absence of the C3aR antagonist SB 290157. Liver function was evaluated by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in conjunction with histopathological characterizations. C3a and C3aR were detected by immunohistochemistry and C5b-9 was assessed by immunofluorescence. IFN-γ and IL4 expressions were determined by flow cytometry and ELISA. The total sensitization rate was 44.1%. TCE sensitization caused liver cell necrosis and inflammatory infiltration, elevated serum ALT and AST, expression of C3a and C3aR, and deposition of C5b-9 in the liver. IFN-γ and IL-4 expressions were up-regulated in spleen mononuclear cells and their serum levels were also increased. Pretreatment with SB 290157 resulted in more inflammatory infiltration in the liver, higher levels of AST, reduced C3aR expression on Kupffer cells, and decreased IL-4 levels while IFN-γ remained unchanged. These data demonstrate that blocking of C3a binding to C3aR reduces IL4, shifts IFN-γ and IL-4 balance, and aggravates TCE-sensitization induced liver damage. These findings reveal a novel mechanism whereby modulation of Th2 response by C3a binding to C3a receptor contributes to immune-mediated liver damage by TCE exposure.     

Anabolic androgenic steroids abuse and liver toxicity

In the athletes the wide use of Anabolic Androgenic Steroids (AAS) cause series damage in various organs, in particular, analyzing the liver, elevation on the levels of liver enzymes, cholestatic jaundice, liver tumors, both benign and malignant, and peliosis hepatis are described. A prolonged AAS administration provokes an increase in the activities of liver lysosomal hydrolases and a decrease in some components of the microsomal drug-metabolizing system and in the activity of the mitochondrial respiratory chain complexes without modifying classical serum indicators of hepatic function. Liver is a key organ actively involved in numerous metabolic and detoxifying functions. As a consequence, it is continuously exposed to high levels of endogenous and exogenous oxidants that are by-products of many biochemical pathways and, in fact, it has been demonstrated that intracellular oxidant production is more active in liver than in tissues, like the increase of inflammatory cytokines, apoptosis and the inhibitors of apoptosis NF- κB and Heat Shock Proteins.     

枯否细胞在非酒精性脂肪肝炎中的发病机制

非酒精性脂肪肝炎(NASH)是一种代谢综合性肝病,是在肝脏细胞脂肪变性基础上进一步诱发炎性反应及纤维化.枯否细胞(KCs)是一种肝巨噬细胞,NASH进展过程中,KCs能够在脂质、内毒素、氧化应激等刺激作用下分泌炎性因子,引发肝细胞炎性反应,损伤肝脏.该文就KCs激活分泌的炎症因子在NASH发病机制中的作用进行详细论述.     

炎症细胞和细胞因子在肝纤维化中的作用研究进展

肝纤维化是肝脏受到损伤后，引起肝脏的炎症免疫反应，继而引起组织自我修复的过程。因促炎介质在肝纤维化的发生及发展中扮演了一个重要的角色，且炎症反应是纤维化的始发阶段，可知炎症细胞不可避免地参与到了肝纤维化中。故本文对巨噬细胞、肥大细胞、中性粒细胞等炎症细胞及转化生长因子β（TGF-β）、血小板源性生长因子（PDGF）、肿瘤坏死因子α （TNF-α）等细胞因子在肝纤维化中的作用研究进展进行综述。