过氧化物酶体增殖物激活受体β/δ激动剂GW0742对硝酸甘油诱导偏头痛大鼠的作用

目的 观察过氧化物酶体增殖物激活受体（peroxisome proliferators-activated receptor β/δ,PPARβ/δ）激动剂GW0742对硝酸甘油诱导偏头痛大鼠的影响.方法 48只（SD大鼠）随机分为模型组、GW0742组和正常对照组.模型组按Tassorelli Cristina法复制大鼠偏头痛模型,GW0742组于造模后30min给药.取三叉神经颈复合体,采用免疫组织化学和Western blot法测定PPARβ/δ及白细胞介素-6（interleukin-6,IL-6）、细胞间粘附分子（intercellular adhesion molecule-1,ICAM-1）、基质金属蛋白酶-9（Matrix metallopeptidase 9,MMP-9）的表达.结果 模型组三叉神经颈复合体中PPARβ/δ的表达明显高于对照组,差异有统计学意义,同时模型组大鼠IL-6、ICAM-1、MMP-9高于对照组,给予GW0742大鼠IL-6、ICAM-1、MMP-9表达明显下降.结论 PPARβ/δ在偏头痛时高度表达,PPARβ/δ激动剂对偏头痛有保护作用.     

免疫性间质性肾炎动物模型肾组织炎症细胞浸润与细胞间粘附分子-1的表达

目的 探讨自身免疫性间质性肾炎的发病机理。方法 用正常小牛肾小管基底膜(bTBM)制造抗TBM型BN大鼠间质肾炎模型,并用单克隆抗体免疫组化ABC法、间接免疫荧光技术,检测炎症细胞及细胞间粘附分子-1(ICAM-1)等。结果 用bTBM免疫后第9天～3周,均可见肾间质有炎症细胞浸润及肾小管上皮细胞有ICAM-1强烈表达,与病理损害程度有同步现象。结论 在免疫性间质性肾炎发生发展中,由ICAM-1介入的细胞免疫起重要作用,但不能除外体液免疫的参与。     

华夏小葱制剂对大鼠脂肪肝形成中 活性氮与细胞因子损伤的影响

［摘要］目的探讨华夏小葱制剂对脂肪肝大鼠的防治作用及其机制。方法SD大鼠60只，随机分为6组：空白对照组，模型对照组，华夏小葱低、中、高剂量组以及复方蛋氨酸胆碱（东宝肝泰片）组，每组10只。用高脂饮食、乙醇溶液并结合皮下注射小剂量四氯化碳的方法建立脂肪肝模型。结果模型对照组大鼠总胆固醇（TC）、三酰甘油（TG）、一氧化氮（NO）、一氧化氮合酶（NOS）、血管内皮生长因子（VEGF） mRNA、细胞间黏附分子（ICAM） 1值显著高于空白对照组（P＜0.01）；华夏小葱低、中、高剂量组及复方蛋氨酸胆碱组TC、TG、NO、NOS、VEGFmRNA、ICAM 1值显著低于模型对照组（P＜0.01或P＜0.05）。结论华夏小葱制剂对脂肪肝大鼠具有防治作用，其机制可能与降脂、减少活性氮及细胞因子对机体的损伤有关。     

脑缺血再灌注损伤的炎症反应机理研究进展

脑缺血再灌注损伤过程包含一系列复杂的病理生理变化,各因素之间又相互影响.本文就近年来备受关注的炎症反应机理做一综述.     

Epidermotropism of T cells correlates with intercellular adhesion molecule (ICAM1) expression in human papillomavirus (HPV)-induced lesions.

Adhesion molecules play an important role in inflammatory reactions. Among them, ICAM1, a ligand for the lymphocyte function-associated antigen (FLA1) of leucocytes, may be expressed by antigen-presenting cells and keratinocytes in various inflammatory disorders. As cell-mediated immune responses play a great role in HPV infections, we investigated the expression of ICAM1 and correlated it with the presence of LFA1-positive cells by immunohistochemistry on serial frozen sections of a series of non-regressing cutaneous and mucosal HPV-induced lesions. ICAM1 expression by keratinocytes was observed only in intensely infiltrated lesions of condylomas and laryngeal papillomas. Its induction was usually correlated with the presence of LFA1-positive cells (mainly CD8-positive cells) which were in close apposition to ICAM1-positive proliferative epithelial cells expressing also, in some cases, HLA-DR antigen. ICAM1 was not correlated with the presence of HPV DNA or viral antigen. In moderately infiltrated lesions, keratinocytes did not express ICAM1, and LFA1-positive cells were not observed in the epidermis. In all lesions, ICAM1 was more intense on endothelial cells than in normal skin; infiltrating cells (lymphocytes and dendritic cells) may also express this antigen but intraepithelial Langerhans cells were devoid of any labelling. These studies provide further evidence that T-lymphocyte mechanisms are important in the host response to HPV-induced lesions. ICAM1 expression correlates with a lesional infiltrate but not with HPV infection and probably results in a more efficient initiation of the immune reaction.     

Early NFkappaB activation is inhibited during focal cerebral ischemia in interleukin-1beta-converting enzyme deficient mice

Our previous study demonstrated that the inhibition of interleukin-1beta (IL-1beta) reduces ischemic brain injury; however, the molecular mechanism of the action of IL-1 in cerebral ischemia is unclear. We are investigating currently the role of NFkappaB during focal cerebral ischemia, using mutant mice deficient in the interleukin-1 converting enzyme gene (ICE KO) in a middle cerebral artery occlusion (MCAO) model. Adult male ICE KO and wild-type mice (n = 120) underwent up to 24 hr of permanent MCAO. Cytoplasmic phospho-NFkappaB/p65 expression in ischemic brain was examined using Western blot analysis and immunohistochemistry. NFkappaB DNA-binding activity was detected using electrophoretic mobility shift assay (EMSA). Furthermore, ICAM-1 expression was examined in both the ICE KO and wild-type mice (WT). Western blot analysis and immunostaining showed that the level of cytosolic phosphorylated NFkappaB/p65 increased after 2 and 4 hr of MCAO in WT mice; however, NFkappaB/p65 was significantly reduced after MCAO in the ICE KO mice (P < 0.05). EMSA showed that NFkappaB DNA-binding activity increased after MCAO in WT mice; but this effect was reduced in the ICE KO mice. The number of ICAM-1-positive vessels in the ischemic hemisphere was greatly attenuated in the ICE KO mice (P < 0.05), which paralleled the results of immunohistochemistry. Our results demonstrate that NFkappaB phosphorylation is reduced in ICE KO mice, suggesting that ICE or IL-1 are involved in early NFkappaB phosphorylation. Because cerebral ischemia induced infarction is significantly reduced in ICE KO mice, we conclude that early NFkappaB phosphorylation plays a disruptive role in the ischemic process.     

Aldosteronism revisited: perspectives on less well-recognized actions of aldosterone

Aldosterone is a mineralocorticoid with protean actions in both epithelial and nonepithelial cells. These include endocrine properties of circulating aldosterone that promote Na(+) resorption at the expense of well-recognized K(+) excretion and less well-recognized Mg(2+) excretion in classic target tissues: kidneys, colon, and sweat and salivary glands. The regulation of adrenal aldosterone secretion by [Mg(2+)](o) is also less well appreciated. More recently recognized endocrine actions of aldosterone include induction of Mg(2+) efflux in exchange for Na(+) in such nonepithelial cells as peripheral-blood mononuclear cells and influence on epithelial cells of the choroid plexus, where aldosterone alters the composition of cerebrospinal fluid that contributes to blood-pressure regulation. An association between primary aldosteronism and idiopathic intracranial hypertension has recently been reported. Extraadrenal steroidogenesis with de novo aldosterone production by the cardiovasculature, where its auto-/paracrine properties may contribute to tissue repair at sites of injury, has been observed. These less well-recognized actions of aldosterone have led to a revival of interest in how this steroid molecule contributes to the pathophysiology of various clinical disorders.     

Oral Tolerance Induced by Enterobacteria Altered the Process of Lymphocyte Recruitment to Intestinal Microvessels: Roles of Endothelial Cell Adhesion Molecules,TGF‐beta and Negative Regulators of TLR Signaling

Objective: Although enterobacteria are implicated in intestinal immune response, there has been no report on how intraluminal pathogens affect lymphocyte recruitment. The aim of this study was to determine how the presence of intestinal flora affects lymphocyte migration to intestine under physiological and lipopolysaccharide (LPS)‐induced inflammatory conditions. Methods: Interaction of T‐cells with ileal microvessels was monitored by using an intravital microscope in mice under germ‐free (GF) and specific pathogen‐free (SPF) conditions. LPS was administered into either the peritoneal cavity or duodenum before lymphocyte injection. Results: Adherence of T‐cells was greater in SPF than in GF mice, indicating that the presence of enterobacteria upregulated migration under physiological conditions. Intraperitoneally administered LPS significantly increased the adherence of T‐cells in both GF and SPF mice accompanied by the expression of adhesion molecules and proinflammatory cytokines. However, intraluminally administered LPS did not enhance the adherence of T‐cells in SPF mice. A significant induction of increase in mRNA expression of IRAK‐M, a negative regulator of TLR4 signaling, and transforming growth factor beta (TGF‐beta), a regulatory cytokine, was observed in SPF mice after luminal LPS treatment. Conclusions: Tolerance to intraluminally administered LPS in the lymphocyte recruitment process was induced by enterobacteria, possibly via the induction of IRAK‐M and TGF‐beta.     

Systemic inflammation and COPD: the Framingham Heart Study

BACKGROUND: The current paradigm for the pathogenesis of COPD includes an ultimately maladaptive local inflammatory response to environmental stimuli. We examined the hypothesis that systemic inflammatory biomarkers are associated with impaired lung function, particularly among those with extensive cigarette smoking. METHODS: Using data from the Framingham Heart Study, we examined cross-sectional associations of systemic inflammatory biomarkers (CD40 ligand [CD40L], intercellular adhesion molecule [ICAM]-1, interleukin [IL]-6, monocyte chemoattractant protein-1, P-selectin, and myeloperoxidase, in addition to C-reactive protein) to impaired lung function. RESULTS: IL-6 was consistently associated with impaired lung function; a 1-SD higher concentration of IL-6 was associated with a 41-mL lower FEV(1) (95% confidence interval [CI], - 61 to - 20) and a borderline 15% higher odds of COPD (odds ratio, 1.15; 95% CI, 0.99 to 1.34). Additionally, P-selectin was associated with lower FEV(1) levels; after adjusting for the other biomarkers, a 1-SD higher concentration of P-selectin predicted an FEV(1) that was on average 19 mL lower (95% CI, - 37 to 0). Including the biomarkers individually as sole exposures in the models generally strengthened the impaired lung function/biomarker association; the relations of ICAM-1 to FEV(1), and ICAM and CD40L to COPD became significant. The observed associations did not vary significantly with smoking history, except that the association between CD40L and COPD appeared greater in individuals with more extensive smoking histories. CONCLUSIONS: Among participants in the Framingham Heart Study, systemic inflammation was associated with lower levels of pulmonary function. Further research into the role of systemic inflammation in the development of pulmonary dysfunction is merited.