炎症反应中性粒细胞凋亡延迟机制研究进展

凋亡的PMN被巨噬细胞吞噬可限制PMN介导的机体损害，PMN凋亡的进程影响着炎症的发展和转归。近来，PMN受体超家族，促／抗凋亡蛋白以及分裂原激活的蛋白激酶家族(MAPKs)在炎症反应PMN凋亡延迟中的作用引起人们的广泛关注。本文阐述了PMN在炎症反应中凋亡延迟机制新进展，希望通过干扰PMN凋亡进程找到一种新的炎症治疗方法。     

肝移植急性排斥反应的细胞及分子免疫学研究进展

目前，肝移植已经成为治疗各种终末期肝病的有效措施，而急性排斥反应（AR）则是肝移植术后最常见的并发症之一，其组织病理学表现主要是：汇管区混合炎症细胞浸润、胆管炎和血管内皮炎。肝移植后AR是一种以细胞免疫为主、体液免疫为辅的特异性免疫反应，但肝脏由于其自身解剖和生理学因素以及一些非实质细胞的影响，使其在发生AR时具有与其他移植器官不同的特点。     

维持性血液透析患者炎症反应的机制及治疗

本文针对血液透析患者炎症反应的发生机制及治疗作了文献综述。     

炎症反应参与瘢痕疙瘩形成的研究进展

瘢痕疙瘩是由感染、创伤、手术诱发或不明诱因导致机体自发形成的过度增生的病理性瘢痕,是机体对真皮损伤的过度组织反应。本文从炎症诱发因素、炎症细胞、炎症介质、炎症效应器及其影响因素等方面介绍了炎症反应参与瘢痕疙瘩形成及通过抑制炎症反应治疗瘢痕疙瘩的研究进展,这些研究结果提示炎症反应既是创面正常愈合的必要环节,也是瘢痕疙瘩形...     

脓毒症发病的炎症反应与免疫紊乱机制

近20年来,人们对脓毒症的发病机制进行了大量的研究,认识到早期和晚期炎症介质引起机体的失控性炎症反应,进一步发展可导致脓毒性休克、多器官功能障碍综合征（MODS）甚至死亡。随着研究的深入,人们又发现在脓毒症的发生与发展过程中机体的免疫功能出现异常,主要原因在于淋巴细胞出现大量凋亡。在炎症和凋亡的发展过程中许多信号转导通路被激活,同时在信号转导通路之间又存在着复杂的交汇作用。本综述拟重点从炎症反应和免疫紊乱等方面阐述脓毒症的发生机制及其病理生理意义。     

肾小球纤维蛋白沉积对肾脏炎症反应的影响及机制研究

目的探讨调控纤维蛋白沉积水平对肾脏炎症反应的影响及其机制。方法实验分脂多糖诱导大鼠肾小球纤维蛋白沉积（LPS组）；氨甲环酸增加纤维蛋白沉积（TL组）：尿激酶减少纤维蛋白沉积（UT组）。肾组织单核细胞趋化蛋白-1（MCP-1）及血管内皮钙黏附蛋白（VE—Cad）mRNA和蛋白质表达分别用RT—PCR和免疫组织化学检测。结果（1）TL组与LPS．UT组纤维蛋白沉积、炎细胞数目差异有统计学意义（P〈0．05）；（2）TL组与LPS，UT组的MCP-1、VE—Cad mRNA及蛋白质表达水平差异亦有统计学意义（P〈0．05）。结论肾小球纤维蛋白沉积具有促炎症作用；纤维蛋白沉积的促炎症作用与其调节MCP-1、VE-Cad表达有关。     

维持性血液透析患者炎症反应的机制及治疗

本文针对血液透析患者炎症反应的发生机制及治疗作了文献综述。     

瘦素,炎症反应与CRF营养不良的研究进展

营养不良是CRF的重要并发症,尤其是CRF透析患者.据报道40%CRF透析患者存在不同程度的蛋白质、能量营养不良,其主要原因为高瘦素血症和机体的炎症反应[1].本文对近年来瘦素,炎症反应与CRF营养不良的研究进展做一综述.     

胆道梗阻后炎症反应发生的过程及机制

胆道梗阻(biliary obstruction)的病因非常复杂,但胆道梗阻后产生的一系列病理生理变化却大致相同,炎症反应作为其中的主要变化在胆道梗阻后造成的肝脏及机体损伤中起着十分重要的作用。了解并理清炎症反应在胆道梗阻后的病理生理变化中的作用及影响对认识这个疾病有着特别的意义。笔者就胆道梗阻后炎症反应产生的过程及机制予以综述。     

烧伤后炎症反应的病因、分子机制及防治对策

烧伤后的炎症反应本质上是机体对烧伤所致组织损伤的一种防御反应,有助于清除创面坏死组织,限制组织损伤扩大和加速组织的修复。受伤部位因微血管通透性增高而出现明显的局部水肿;当烧伤面积≥30%TBSA时,还可引起全身性的微血管通透性升高,并伴有不同程度的全身反应,如发热、血中白细胞增多、肝脏合成急性期反应蛋白等。这时大量炎症介质的释放可激活中性粒细胞(PMN)和血管内皮细胞(VEC),若抗炎介质产生相对不足则可造成组织和器官的损伤,引发多脏器功能不全甚至死亡[1]。可见,严重烧伤是以全身性炎症反应为特征的全身性疾病,在宏观上仔…     

腹膜粘连的细胞机制研究进展

腹膜粘连（PA）是由手术、腹膜炎症、腹膜透析等引起的腹腔内受损组织和器官间的异常纤维性粘连带,其中手术是引发PA的主要原因。PA可引起不孕、肠梗阻、肠穿孔等临床并发症,二次松解手术为主要治疗方案,但易复发且存在多种并发症风险。近年来开发出一系列用于PA预防与治疗的药物和屏障材料,但防治效果尚不满意。抗PA药物会增加出血的风险,并抑制正常免疫功能,屏障材料虽然一定程度上缓解了PA进展,但因其不能持久覆盖腹膜损伤部位、降解不彻底等问题,不能达到抗PA的理想效果。因此在PA防治上需要新的突破。近期的研究表明PA是一系列事件综合作用的结果,包括血管损伤、血小板聚集、凝血级联反应、纤维蛋白沉积等过程,最终纤维蛋白和细胞外基质沉积形成粘连带,后期形成收缩性瘢痕并引发临床症状,上述事件中,参与PA的各种细胞发挥了关键作用。腹膜微环境中分布有腹膜间皮细胞（PMC）、中性粒细胞、嗜酸性粒细胞、T淋巴细胞、巨噬细胞、肥大细胞等。生理条件下,这些细胞成分对腹膜微环境的动态稳定具有重要意义。当细菌和异物侵入腹膜腔时,纤维蛋白和炎性细胞随腹腔液渗出以限制、清除并吸收异物,最终纤维蛋白被吸收,腹膜损伤正常愈合。病...     

Fluence rate as a modulator of PDT mechanisms

BACKGROUND AND OBJECTIVES: Molecular oxygen in the tissue to be treated by photodynamic therapy (PDT) is critical for photodynamic cell killing. The fluence rate of PDT light delivery has been identified as an important modulator of tissue oxygenation and treatment outcome. This article provides supporting evidence for the role of fluence rate in PDT and discusses the underlying mechanisms. STUDY DESIGN/MATERIALS AND METHODS: Intratumoral pO2 was measured polarographically in murine tumors before and during PDT light treatment using the Eppendorf pO2 Histograph. Tumor response as a function of fluence rate and fluence was also assessed in murine tumor models. Changes in vascular permeability as a function of fluence rate were determined in murine tumors by measuring tumor uptake of fluorescent beads (200 nm diameter). RESULTS: Severe oxygen depletion is shown to occur within seconds of illumination at a fluence rate of 75 mW/cm2 in radiation-induced fibrosarcoma (RIF) tumors photosensitized with AlPcS2. This effect was reversible and consistent with photochemical oxygen depletion, which has been shown by us and others to be fluence rate dependent. It is demonstrated that fluence rate affects the PDT tumor response in the Colon 26 tumor model, high fluence rate diminishing or even totally inhibiting tumor control, low fluence rate promoting tumor control. The influence of fluence rate is not restricted to cytocidal effects, but can also be seen in sublethal conditions such as vascular permeability. CONCLUSIONS: Fluence rate of PDT light delivery exerts far-reaching control upon treatment outcome through its oxygenation modulating properties and possibly other mechanisms yet to be identified. This has been shown to be true in the preclinical and clinical setting. Further development of in situ dosimetry will be necessary to take full advantage of these discoveries.     

Cellular and molecular mechanisms of inflammation and thrombosis.

In the last 20 years, the cellular and molecular mechanisms of inflammation and thrombosis have been characterised. These are essentially cell adhesion processes which are regulated by vascular endothelium. Many of the cell adhesion molecules and leucocyte chemoattractants expressed and generated at sites of inflammation have been sequenced and cloned. These inflammatory molecules work together in concert to mediate the adhesion between leucocytes, platelets and vascular endothelium which occurs during the occlusive, thromboembolic, reperfusion and septic complications of atherosclerotic and diabetic vascular diseases. This review aims to summarise our current understanding of the molecular basis of these disorders and the therapeutic implications.     

Relationships among inflammation nutrition and physiologic mechanisms establishing albumin levels in hemodialysis patients

BACKGROUND: Serum albumin concentration is a balance among its synthesis rate, fractional catabolic rate (FCR), distribution, dilution in the plasma pool and external loss. The physiologic bases for establishing the level of serum albumin in hemodialysis patients have not been defined despite the association of hypoalbuminemia with excess mortality. Albumin concentration is associated with the levels of several acute phase proteins (APPs), C-reactive protein (CRP), alpha1 acid glycoprotein (alpha1 AG), or ceruloplasmin, and with nutritional markers, such as normalized protein catabolic rate (nPCR). METHODS: To establish the relationship among parameters that regulate albumin levels and markers of nutrition and inflammation, we injected [125I]-albumin, into 64 hemodialysis patients enrolled in the HEMO study to measure albumin distribution, synthesis and FCR. These variables were related to the levels of acute phase proteins (APPs), nPCR, body mass index (BMI), external albumin loss as well as demographic variables. Albumin distribution, synthesis and FCR were calculated from kinetic modeling, as was the initial plasma volume (PV). Serum albumin, transferrin, CRP, ceruloplasmin and alpha1 AG were measured weekly. Dialysate was collected during one dialysis each week to measure albumin loss. Results were analyzed by multiple linear regression. RESULTS: Albumin concentration correlated with its synthesis rate and FCR, but not with PV or its distribution between the vascular and extravascular pools. Albumin concentration also correlated with nPCR and alpha1 AG. However, albumin synthesis was directly related most strongly to PV and BMI (or nPCR), but not to levels of APPs. By contrast, albumin FCR correlated positively with both alpha1 AG and ceruloplasmin. CONCLUSION: Albumin concentration in dialysis patients changes with inflammation and nutritional status through their effects on albumin catabolism and synthesis, respectively. Within the range of albumin levels in these patients, nutritional variables primarily affected albumin synthesis while inflammation caused hypoalbuminemia by increasing albumin FCR. Albumin synthesis also increased in proportion to PV. The result of this is that PV expansion does not contribute to hypoalbuminemia.     

糖尿病骨质疏松的细胞及分子机制研究进展

糖尿病患者骨质疏松的发生源于骨代谢状态改变,与胰岛素、胰岛素样生长因子-1(IGF-1)的作用有关。此外,高血糖毒性刺激细胞分泌肿瘤坏死因子α(TNF-α)、巨噬细胞集落刺激因子（MCSF)、核因子kB受体活化因子配体（RANKL)、血管 内皮生长因子-A( VEGF-A)等破骨源性细胞因子也发挥重要作用。     

FK778: new cellular and molecular mechanisms of action

PURPOSE: The new malononitrilamide FK778 is currently being evaluated as an immunosuppressant for organ transplantation. Its main mechanism is inhibition of a pivotal enzyme of pyrimidine biosynthesis. This report revealed new mechanisms of action on different cell types involved in acute and chronic allograft rejection. METHODS: Purified Brown-Norway rat aortic endothelial cell (EC) cultures were pretreated with several concentrations of FK778. Endothelial adhesion molecule expression (ICAM-1/VCAM-1) stimulated with TNF-alpha was quantified by immunofluorescence. Purified Lewis rat lymphocytes (LC) incubated with FK778 were stimulated via TCR/CD28 signals, and CD25 expression was quantified using FACS analysis. Uridine addition was used in all assays to reverse the pyrimidine synthesis blockade. Lymphocyte-EC interaction was assessed by micromanipulator-assisted single-cell adhesion assays. Finally, smooth muscle cell (SMC) proliferation and migration was analyzed. Uridine addition was used in all assays to reverse the pyrimidine synthesis blockade. RESULTS: TNF-alpha stimulation and TCR/CD28 co-stimulation significantly increased EC ICAM-1/VCAM-1-expression and LC CD25 surface expression, respectively. These effects were dose-dependently inhibited by FK778 and were not reversed by the addition of uridine. FK778 dose-dependently attenuated LC adhesion to allogeneic EC. The dose-dependent inhibition of SMC proliferation by FK778 was abolished by uridine addition, whereas the inhibitory effect on SMC migration was not affected by uridine supplementation. CONCLUSIONS: FK778 directly reduced endothelial adhesion molecule up-regulation, inhibited lymphocyte activation, and attenuated lymphocyte-endothelium interactions, critical early steps in graft rejection. These effects were separate from the blockade of pyrimidine synthesis. The antiproliferative potency of FK778 on SMC may be an important mechanism to inhibit the fibroproliferative lesions of chronic organ rejection.     

退变腰椎黄韧带超微结构的改变与分二子机制的研究进展

腰椎黄韧带特殊的组织结构和生理功能,致使其较易发生黄韧带肥厚、钙化和骨化等生理性和病理性改变.其主要表现为弹力纤维明显减少,胶原纤维显著增加,并出现骨化、钙盐沉积、透明变性、囊性变以及软骨细胞、成纤维细胞和毛细血管的增生等超微结构的改变.最近的研究表明,转化生长因子(FGFβs)、骨形态发生蛋白(BMP)、血管内皮生长因子(VEGF)和成纤维生长因子(FGF)等生长因子在黄韧带退变的病理过程中起重要作用.     

Osteoporosis in diabetes mellitus: Possible cellular and molecular mechanisms

Osteoporosis,a global age-related health problem in both male and female elderly,insidiously deteriorates the microstructure of bone,particularly at trabecular sites,such as vertebrae,ribs and hips,culminating in fragility fractures,pain and disability.Although osteoporosis is normally associated with senescence and estrogen deficiency,diabetes mellitus(DM),especially type 1 DM,also contributes to and/or aggravates bone loss in osteoporotic patients.This topic highlight article focuses on DM-induced osteoporosis and DM/ osteoporosis comorbidity,covering alterations in bone metabolism as well as factors regulating bone growth under diabetic conditions including,insulin,insulin-like growth factor-1 and angiogenesis.Cellular and molecular mechanisms of DM-related bone loss are also discussed.This information provides a foundation for the better understanding of diabetic complications and for development of early screening and prevention of osteoporosis in diabetic patients.     

皮肤老化机制及老化状态评估方法的研究进展

<正>衰老是一种不可避免的生理变化过程。随着人年龄的增长,人体内大分子和细胞的生化调节能力不断降低,相关器官和组织功能逐渐衰退。就人体最大的器官皮肤而言,衰老意味着角质形成细胞、成纤维细胞数量减少与功能下降,弹性蛋白和胶原蛋白合成减少及萎缩,从而使皮肤变得缺乏弹性、松弛、粗糙,并伴有不规则色素沉着、干燥等现象。随着社会的发展,人类的平均寿命在不断提     

炎症与椎间盘退行性变关系的研究进展

椎间盘退行性变(IDD)是引起椎间盘突出、椎管狭窄等相关疾病的病理基础,也是导致腰腿痛的主要原因之一[1].椎间盘髓核组织蛋白多糖减少、纤维环裂隙出现,导致髓核组织从纤维环的裂口中突出,引起相应的免疫炎性反应,且同时脊髓和神经根受到突出髓核的压迫,导致患者出现腰腿痛症状.