中药干预脑缺血后炎症反应的临床研究进展

中医药可通过抑制炎症细胞因子的合成、下调炎症介质及黏附分子的表达、抑制炎症细胞的功能等多种途径干预脑缺血后炎症反应，发挥脑保护作用。     

Ischemic heart disease in systemic inflammatory diseases. An appraisal

Systemic inflammatory diseases are inflammatory syndromes that are associated with increased cardiovascular morbidity and mortality. The link between inflammatory and cardiovascular diseases can be attributed to coexistence of classical risk factors and of inflammatory mechanisms activated in systemic inflammatory diseases and involving the immune system. Yet, clinical implications of these findings are not entirely clear and deeper knowledge and awareness of cardiac involvement in inflammatory diseases are necessary. The aims of this review are to summarize cardiac involvement in systemic inflammatory diseases and to identify areas where evidence is currently lacking that deserve further investigation in the future.     

Update on the genetics of inflammatory bowel disease

There is a general consensus that interplay of genetic and environmental factors leads to an overactive mucosal immune response, which mediates the tissue damage in inflammatory bowel disease. Ethnic aggregation of inflammatory bowel disease (particularly, increased incidence and prevalence in the Ashkenazim), familial aggregation of inflammatory bowel disease, and greater concordance for inflammatory bowel disease in monozygotic twins than dizygotic twins are 3 lines of evidence for a central role of genetic factors in the pathogenesis. The genetics of inflammatory bowel disease cannot be explained by simple Mendelian genetics; it is characterized by incomplete penetrance, multiple susceptibility loci and genetic heterogeneity. Unraveling the complex genetics of inflammatory bowel disease is a daunting challenge, but the perseverance of inflammatory bowel disease gene hunters has produced commendable results in recent years. Since 1996, the field of inflammatory bowel disease genetics has progressed from publication of the first systematic genome searches for inflammatory bowel disease susceptibility loci to the identification of Crohn disease-associated genetic variants in CARD15/NOD2. Strategies for finding additional inflammatory bowel disease genes include taking advantage of the greater resolution and power of linkage disequilibrium mapping, mapping by admixture disequilibrium in African-American and Hispanic-American populations, stratifying genetic analyses by genotypes at known inflammatory bowel disease loci, and refining inflammatory bowel disease phenotypes to reduce genetic heterogeneity and simplify the search for additional inflammatory bowel disease genes.     

细胞因子信号转导抑制因子1在肝脏炎症性疾病发生发展中的作用机制

肝脏炎症性疾病的发生与自身免疫和炎症反应有关,细胞因子信号转导抑制因子1(SOCS1)作为一种细胞信号的负反馈调节因子,其在炎症性疾病的发生发展中起到关键作用。介绍了SOCS1在自身免疫与炎症反应中的作用机制,简述其在肝脏炎症性疾病如病毒性肝炎、非酒精性脂肪性肝炎等疾病发生、发展中的作用。分析表明SOCS1在炎症反应中的异常表达与细胞因子受体、Toll样受体和激素受体信号的调控有关,从而导致炎症性疾病的发生,因此SOCS1作为肝脏炎症性疾病诊断和治疗的辅助手段具有潜在的发展前景。     

Thrombosis and inflammatory bowel disease.

Interaction between thrombosis and inflammation is increasingly recognized. With this, interest has arisen in the role of thrombosis in inflammatory conditions, including the inflammatory bowel diseases. Although the association between active inflammatory bowel disease and thromboembolic complications has long been known, there has been a resurgence in research into the role of thrombosis and the hemostatic system in the pathogenesis of both ulcerative colitis and Crohn's disease. Here we review the increased frequency of thromboembolic complications occurring in patients with inflammatory bowel disease; whether thrombosis might play a part in the initiation and maintenance of inflammation in inflammatory bowel disease; abnormalities of the coagulation system found in patients with inflammatory bowel disease; platelet dysfunction in inflammatory bowel disease; the mechanisms by which hemostatic processes might be proinflammatory in inflammatory bowel disease; and how these interactions might impact not only on the prevention of complications, but also on the treatment of the underlying inflammation in inflammatory bowel disease.     

Antiinflammatory therapies other than corticosteroids

Antiinflammatory therapy for chronic obstructive pulmonary disease (COPD) can be directed at several stages of the inflammatory process. Much attention has been focused on blocking the damaging effects of toxic mediators released by inflammatory cells, including antioxidants and antiproteases. An alternate strategy is to block the recruitment of inflammatory cells into the lung, such as by inhibiting the production of chemotactic factors driving inflammatory cell recruitment, the ability of inflammatory cells to respond to chemotactic factors, and the ability of inflammatory cells to migrate. Moreover, mediators released by inflammatory cells, particularly tumor necrosis factor-alpha, probably have systemic effects in COPD. Blocking the release of these cytokines or blocking their ability to act on distal tissues represents another potential therapeutic option. It is also important to recognize that the various components of the inflammatory response are not independent. The action of proteases released by inflammatory cells, for example, can generate chemotactic factors, lead to activation of inflammatory cells, and modulate repair responses. The complex network of regulatory molecules that controls the inflammatory response, therefore, presents a number of potential therapeutic targets with the promise of altering the disease process in COPD.     

A clinicopathological study of inflammatory pseudotumors of the liver with special reference to vessels

BACKGROUND/AIMS: Inflammatory pseudotumor of the liver is rare, and patients with inflammatory pseudotumor frequently undergo unnecessary surgical resection as a result of misdiagnosis of malignancy. In this study, we therefore investigated inflammatory pseudotumor clinicopathologically to clarify its characteristics. METHODOLOGY: Twenty patients including 3 with inflammatory pseudotumor and 17 with various malignant liver tumors were studied. We further investigated tumor vessels by means of immunohistochemistry using monoclonal antibodies against CD34, factor VIII-related antigen and alpha-smooth muscle actin. RESULTS: Although serum levels of alkaline phosphatase were significantly higher in inflammatory pseudotumor patients than in other patients, the laboratory data alone could not precisely distinguish inflammatory pseudotumor from other hepatic tumors. On imaging studies such as ultrasonography and computed tomography, significant changes in tumor size, especially size reduction, during relatively short follow-up periods were often observed in inflammatory pseudotumor but not in other liver tumors. An enhancement of the peripheral regions of inflammatory pseudotumor was frequently observed in the early phase of contrast-medium dynamic computed tomography. This might be due to abnormal vessels located in the peripheral regions of inflammatory pseudotumor which might result from obliteration of some pre-existing vessels in portal tracts within inflammatory pseudotumor. Immunohistochemical analysis further revealed that abnormal vessels in the peripheral regions of inflammatory pseudotumor were positively stained with CD34, factor VIII-related antigen and alpha-smooth muscle actin as were tumor sinusoids within hepatocellular carcinoma and tumor capillaries in other malignant liver tumors. CONCLUSIONS: Although inflammatory pseudotumor seems to have some features in imaging studies, a biopsy is needed for a correct diagnosis of inflammatory pseudotumor.     

Prothrombotic inherited abnormalities other than factor V Leiden mutation do not play a role in venous thrombosis in inflammatory bowel disease

OBJECTIVES: Because the incidence of thromboembolism is increased in patients with inflammatory bowel disease, we attempted to assess the role of prothrombotic inherited coagulation abnormalities in the development of thrombosis. METHODS: Four populations were compared: 15 patients with inflammatory bowel disease and a previous venous thrombosis, 58 control patients with inflammatory bowel disease but without thrombosis, 110 patients without inflammatory bowel disease but with previous deep venous thrombosis, and 84 healthy subjects. Inherited and acquired risk factors of venous thrombosis, e.g., factor V Leiden and prothrombin 20210A mutations, C677T methylenetetrahydrofolate reductase polymorphism, a polymorphism located in exon 13 of factor V gene, inflammatory and hypercoagulability markers were studied in each population. RESULTS: In the study, 14.3% of thrombotic patients with inflammatory bowel disease had factor V Leiden mutation versus 0% of control patients with inflammatory bowel disease (p = 0.04), 15.5% of thrombotic patients without inflammatory bowel disease (NS) and 3.6% of the healthy controls. A total of 14% of thrombotic patients with inflammatory bowel disease and 11.8% of thrombotic patients without inflammatory bowel disease carried prothrombin 20210A mutation, compared to 1.7% of control patients with inflammatory bowel disease; however, the difference was just below significance. Other inherited coagulation abnormalities were not statistically significantly different among the four populations. CONCLUSIONS: Our study confirms that factor V Leiden mutation increases the risk for thrombotic events but is not more frequent in patients with inflammatory bowel disease. Our results do not support the role of other thrombotic risk factors.     

Nutritional modulation of the inflammatory bowel response

Crohn's disease and ulcerative colitis represent distinct phenotypic forms of inflammatory bowel disease and continue to be a common cause of morbidity. The corticosteroids and the immunomodulatory drugs, which are the basis of treatment for the inflammatory bowel diseases, do not assure always satisfactory outcomes. Nutrition has been used in order to modify the inflammatory response of various chronic inflammatory diseases, including Crohn's disease and ulcerative colitis. In the pathogenesis of inflammatory bowel diseases, the intestinal microflora and the intestinal mucosal disorders play a crucial role. Also, the release of reactive oxygen species is a significant factor of initiation and preservation of the inflammatory reaction in these diseases. The advantages of the nutritional treatment derive from the sequestration of intraluminal agents which may promote the inflammatory bowel response or, alternatively, nutrition is able to modify the immune response, reducing the uncontrolled inflammatory reaction. Furthermore, nutrition can enhance the mucosal barrier function and consists a significant source of antioxidants. This review focuses on certain nutritional components that modulate the inflammatory response of the bowel and aims to present a rational thesis regarding the use of nutritional agents in the management of inflammatory bowel diseases.     

趋化因子及其受体与冠心病关系的研究进展

动脉粥样硬化(AS)是慢性炎性及代谢性疾病,脂质沉积和炎性细胞浸润至血管内皮下是形成AS的主要原因,但是炎性细胞浸润的机制尚未阐明。许多国内外研究表明,趋化因子对单核细胞、巨噬细胞、T细胞等炎性细胞的迁移、活化在AS炎症反应中起重要作用。新近研究证实,趋化因子可促使血管平滑肌细胞增殖以及炎症因子和基质金属蛋白酶的合成,促进斑块不稳定的关键环节。本文就趋化因子及其受体在AS发生发展中的作用予以综述。     

Increased Expression of Long Pentraxin PTX3 in Inflammatory Bowel Diseases

The aims of this study were to investigate the expression of pentraxin-3 in inflamed gastrointestinal tissue in patients with inflammatory bowel diseases and to elucidate the usefulness of plasma pentraxin-3 level as an inflammation marker in patients with inflammatory bowel diseases. Pentraxin-3 immunoreactivity was found in infiltrating neutrophils and vessels in the inflamed gut. Plasma pentraxin-3 concentration in patients with active inflammatory bowel diseases was significantly higher than that of normal subjects and patients with inactive inflammatory bowel diseases. Significant positive correlations of clinical disease activity with plasma pentraxin-3 concentration and serum CRP concentration were found in patients with inflammatory bowel diseases. Pentraxin-3 is directly produced from the inflamed gut in inflammatory bowel diseases. In conclusion, plasma pentraxin-3 concentration is a useful marker for understanding the disease activity in patients with inflammatory bowel diseases.     

Glucose metabolism of injured skeletal muscle: the contribution of inflammatory cells

Wounded muscle which has increased glucose uptake is infiltrated with a large number of inflammatory cells. Macrophages which are the predominant inflammatory cells in wounded muscle can increase glucose oxidation by epididymal fat pads. Therefore, the possibility that inflammatory cells could also alter glucose metabolism in skeletal muscle was investigated. Peritoneal inflammatory cells (67% macrophages, 7% lymphocytes, 15% polymorphonuclear leukocytes, and 11% eosinophils) were elicited with a 1% sodium caseinate solution. Extensor digitorum longus muscles, were incubated alone, in the presence of inflammatory cells or in an inflammatory-cell-conditioned media. Similar incubations were performed using epididymal fat pads. In addition, inflammatory cells were incubated alone. The present studies confirmed the previous finding that inflammatory cells release a factor(s) that increases glucose oxidation in epididymal fat pads. The coincubation of inflammatory cells with skeletal muscle resulted in a 22% increase in glucose uptake and a 19% increase in the conversion of glucose to lactate compared to the sum of these processes for muscle or inflammatory cells incubated alone. In addition, this study showed that the incubation of skeletal muscle in inflammatory-cell-conditioned medium produced a 117.6% increase in glucose uptake and a 147% increase in the conversion of glucose to lactate. Therefore, inflammatory cells can increase glucose metabolism in skeletal muscle through the release of a soluble factor(s). This effect does not require a direct contact of the inflammatory cells with skeletal muscle.     

肺癌转移的炎症微环境机制研究进展

近年来,炎症微环境在肿瘤进展过程中的作用日益受到重视,多项研究表明肺癌的炎症微环境在肺癌的转移中起着重要作用.炎症微环境可以通过直接或间接促进肿瘤血管生成、细胞增殖和抑制细胞凋亡进程,从而促进肺癌的转移,而这一过程主要是借助炎症因子、炎症信号通路等途径而实现的.本文就近年来肺癌转移的炎症微环境机制相关的研究进展作一综述.     

Development of an ex vivo cellular model of rheumatoid arthritis: critical role of CD14-positive monocyte/macrophages in the development of pannus tissue

OBJECTIVE: To establish an ex vivo cellular model of pannus, the aberrant overgrowth of human synovial tissue (ST). METHODS: Inflammatory cells that infiltrated pannus tissue from patients with rheumatoid arthritis (RA) were collected without enzyme digestion, and designated as ST-derived inflammatory cells. Single-cell suspensions of ST-derived inflammatory cells were cultured in medium alone. Levels of cytokines produced in culture supernatants were measured using enzyme-linked immunosorbent assay kits. ST-derived inflammatory cells were transferred into the joints of immunodeficient mice to explore whether these cells could develop pannus. CD14 and CD2 cells were depleted by negative selection. RESULTS: Culture of ST-derived inflammatory cells from 92 of 111 patients with RA resulted in spontaneous reconstruction of inflammatory tissue in vitro within 4 weeks. Ex vivo tissue contained fibroblasts, macrophages, T cells, and tartrate-resistant acid phosphatase-positive multinucleated cells. On calcium phosphate-coated slides, ST-derived inflammatory cell cultures showed numerous resorption pits. ST-derived inflammatory cell cultures continuously produced matrix metalloproteinase 9 and proinflammatory cytokines associated with osteoclastogenesis, such as tumor necrosis factor alpha, interleukin-8, and macrophage colony-stimulating factor. More importantly, transferring ST-derived inflammatory cells into the joints of immunodeficient mice resulted in the development of pannus tissue and erosive joint lesions. Both in vitro development and in vivo development of pannus tissue by ST-derived inflammatory cells were inhibited by depleting CD14-positive, but not CD2-positive, cells from ST-derived inflammatory cells. CONCLUSION: These findings suggest that overgrowth of inflammatory cells from human rheumatoid synovium simulates the development of pannus. This may prove informative in the screening of potential antirheumatic drugs.     

The pathogenesis of inflammatory polyps

Eighty-six consecutive colonic resection specimens for inflammatory bowel disease were studied to determine the modes of inflammatory polyp formation. The two major groups of inflammatory polyps were (1) polypoid mucosal tags due to undermining ulceration and (2) mature inflammatory polyps composed of mucosa, muscularis mucosae, and a submucosal core. Mature inflammatory polyps were derived from polypoid mucosal tags after regeneration and the adjacent mucosa showed regenerative changes and submucosal scarring. The study confirms that ulceration which undermines the muscularis mucosae is the major precursor of inflammatory polyps. Presented at the meeting of the International Academy of Pathology, Toronto, Canada, March 1985. Supported by the Pencer Fund and the Foothills Hospital Foundation.     

凝血酶与缺血性脑损害的炎症反应

近年的研究发现 ,凝血酶是一种多功能丝氨酸蛋白酶 ,除了参与凝血过程外 ,还刺激细胞产生各种炎症反应所必需的炎症介质 ,参与炎症反应过程 ,加重缺血性脑损害的炎症反应 ,进一步产生神经功能损害。文章综述了近年来国内外相关研究的进展和凝血酶对炎症反应的作用机制 ,旨在为临床治疗提供新的线索。     

炎性细胞因子与慢性阻塞性肺疾病关系的研究进展

慢性阻塞性肺疾病(COPD)是呼吸系统常见疾病,但其确切发病机制目前尚不十分清楚,多种炎性细胞及炎性细胞因子参与的慢性炎性反应被认为是其核心病理改变。本文从常见炎性细胞因子的生物学特性、生物学功能及其与COPD的关系等进行综述。     

Inflammatory rheumatic disease and smoking are predictors of aortic inflammation: a controlled study of biopsy specimens obtained at coronary artery surgery

OBJECTIVE: Several inflammatory rheumatic diseases are associated with accelerated atherosclerosis. Atherosclerosis may result from systemic and/or local vascular inflammation. The aim of this study was to evaluate the occurrence of chronic inflammatory infiltrates in the aortas of patients with and those without inflammatory rheumatic disease who had undergone coronary artery bypass graft (CABG) surgery, and to assess the relationship between the infiltrates and other factors thought to play a role in atherosclerosis, such as smoking. METHODS: Aortic specimens routinely removed during CABG surgery in 66 consecutive patients with inflammatory rheumatic disease and 51 control patients without inflammatory rheumatic disease were examined by light microscopy for the occurrence, location, and severity of chronic inflammatory infiltrates and atherosclerotic lesions. RESULTS: Mononuclear cell infiltrates in the inner adventitia (apart from those localized along the epicardium) were more frequent in the group of patients with inflammatory rheumatic disease (47% versus 20%; P = 0.002, odds ratio [OR] OR 3.6, 95% confidence interval [95% CI] 1.6-8.5), and the extent of these infiltrates was greater. Multivariate analyses revealed that the occurrence of mononuclear cell infiltrates was associated with inflammatory rheumatic disease (OR 2.99, P = 0.020) and current smoking (OR 3.93, P = 0.012), and they were observed in 6 of 7 patients with a history of aortic aneurysm. Inflammatory infiltrates in the media were seen only in patients with inflammatory rheumatic disease. The frequency of atherosclerotic lesions, inflammation within the plaques, and epicardial inflammatory infiltrates in the 2 groups was equal. CONCLUSION: Among aortic samples collected during CABG surgery, those obtained from patients with inflammatory rheumatic disease had more pronounced chronic inflammatory infiltration in the media and inner adventitia than those obtained from control patients. Current smoking was an independent predictor of chronic inner adventitial infiltrates. The infiltrates may represent an inflammatory process that promotes atherosclerosis and formation of aneurysms.     

NF-κB在肠道炎症和免疫应答中的作用

NF-κB是一种多向性的转录因子,它参与多种炎症和免疫应答相关分子基因的表达,同时也参与调控细胞的增殖和分化。活动期炎症性肠病病人NF-κB持续升高显示,通过调节NF-κB活性可作为潜在的药物治疗策略。本文对NF-κB在肠道的炎症和免疫应答中的作用做一综述。     

Skeletal muscle pathology in 2 siblings infected with Toxoplasma gondii

Skeletal muscle can be the site of inflammatory diseases that lead to muscle weakness, pain, and increased myogenic serum enzymes. Most of these inflammatory myopathies are idiopathic. In some cases inflammatory myopathies are due to infectious agents. We describe the pathological aspects of muscle biopsies of 2 Brazilian siblings who acquired toxoplasmosis at the same time and in similar conditions. One developed a tetraplegia that was confirmed to be due to inflammatory myositis due to toxoplasma. The other developed myocarditis, with heart failure, without skeletal muscle weakness. In both cases many toxoplasma organisms were observed in the muscle biopsies, but in case 1 only was there an inflammatory myopathy with myofiber necrosis; the inflammatory cells were predominantly macrophages with some CD4+ cells and rare CD20+ cells. In case 1, expression of CD54 was observed in many inflammatory cells as well in endothelial cells, but only in endothelial cells in case 2. After treatment with clindamycin and corticosteroids both cases had only partial improvement, case 1 with a residual muscle weakness and case 2 with residual cardiac insufficiency (requiring digoxin). These cases show that the presence of the parasite in myofibers is not enough to induce an inflammatory myositis with muscle cell necrosis. This suggests that immunological disturbances may contribute to the development of inflammatory myositis due to toxoplasma.