锂对中枢神经和血液系统的作用（二）

许多学者报道抑郁使得脑内脑源性神经营养因子（BDNF）减少，锂通过增加脑内的BDNF而发挥作用。锂和丙戊酸盐选择性地激活神经元内脑源性神经营养因子促进因子Ⅳ，提高海马内BDNF的水平。锂和匹鲁卡品诱导的癫痫持续状态与大鼠脑BDNF广泛增高有关。锂也能增加大鼠海马内的神经生长因子（NGF），但丙戊酸和安非他命都不改变脑内的NGF。     

胍丁胺干预对变态反应性脑脊髓炎的胶质纤维酸性蛋白表达、γ-干扰素和白介素-10水平影响的实验研究

目的观察胍丁胺(神经递质,抗炎药)对实验性变态反应性脑脊髓炎中枢神经系统内胶质纤维酸性蛋白表达及γ-干扰素和白介素-10水平的影响。方法用GPSCH免疫Wistar大鼠建立实验性变态反应性脑脊髓炎动物模型,于免疫当日,开始分别予25,50,100 mg.kg-1胍丁胺,腹腔注射,每天1次,连续14 d。比较各组行为学变化,用免疫组化法观察脑和脊髓组织中的胶质纤维酸性蛋白的表达;用双抗夹心ELISA法测定实验性变态反应性脑脊髓炎大鼠脑和脊髓组织内细胞因子γ-干扰素和白介素-10的水平。结果与模型组比较,胍丁胺给药14 d可明显降低变态反应性脑脊髓炎大鼠的发病率,改善其临床症状;脑和脊髓组织中,胶质纤维酸性蛋白表达增高(P<0.05),γ-干扰素水平降低和白介素-10水平升高(P<0.05或<0.01)。结论胍丁胺能促进胶质纤维酸性蛋白表达,调节实验性变态反应性脑脊髓炎中的Th1/Th2比例平衡,降低γ-干扰素,升高白介素-10。     

2型糖尿病并发抑郁症与脑源性神经营养因子的相关性研究

目的探究2型糖尿病并发抑郁症与脑源性神经营养因子的相关性。方法将我院2009年4月至2011年4月之间收录的80例2型糖尿病并发抑郁症患者作为研究组,并选取同期的80例2型糖尿病非抑郁患者为对照1组,而选取同期80名健康对象为对照2组。三组的患者均空腹采血,并采取常规的蛋白酶K快速裂解法进行提取外周血的基因组DNA,然后采用聚合酶链式反应-限制性片段长度多态性法进行有效的检测脑源性神经营养因子基因Va166Met的多态性,并采取ELISA法进行测定血清中的脑源性神经营养因子的水平含量。结果通过三组的对比分析,研究组和对照1组及对照2组患者血清中的脑源性神经营养因子含量分别为(75.6±4.4)pg/mL、(79.5±5.3)pg/mL、(86.4±3.4)pg/mL,三组的数据比较具有明显的差异(P<0.05),统计学有意义。而三组的患者脑源性神经营养因子基因Va166Met的多态性基因型和等位基因的频率比较具有明显的差异(P<0.05),统计学有意义;不同脑源性神经营养因子基因Va166Met患者的脑源性神经营养因子含量比较比较明显的差异(P<0.05)。结论脑源性神经营养因子基因Va166Met的多态性是2型糖尿病并发抑郁症的易感因素,且携带Met/Met基因的纯合子患者较携带Val/Val基因的纯合子和Val/Met基因的杂合子患者更容易发生抑郁症,而且患者血清中的脑源性神经营养因子含量受到脑源性神经营养因子基因Va166Met多态性的影响,而且与糖尿病并发抑郁症的发生有关联。     

脑源性神经营养因子前体的研究进展

神经营养因子是一种分泌性多肽类生长因子家族,参与神经系统的多种生理功能活动,研究发现成熟的脑源性神经营养因子与其前体分子具有不同的生物学活性,它们的受体以及介导的细胞内信号通路也大相径庭。本文对近年来关于脑源性神经营养因子前体分子的研究进展予以综述,着重讨论其体内分布、生物合成与分泌、生物学活性以及与疾病的联系。研究脑源性神经营养因子前体分子在生理和病理状态下的作用将对未来的药物开发和神经系统疾病的治疗具有重要的意义。     

脑源性神经营养因子与缺血性损伤

脑源性神经营养因子是神经营养因子(NTFS)中的一种，其在神经元损伤后再生修复和防止神经细胞退行性变等方面发挥了重要作用。许多研究表明，BDNF对限制脑缺血后分解代谢产物所产生的损伤级联反应有重要作用。本就其可能的作用机制及未来前景展望作一综述。     

血浆脑钠肽水平对诊治心源性与肺源性呼吸困难的价值

目的探讨血浆脑钠肽水平对诊治心源性呼吸困难、肺源性呼吸困难的价值。方法选择2010年1月至2011年1月90例呼吸困难的住院患者,分为心源性呼吸困难组48例、肺源性呼吸困难组42例,分别检测血浆脑钠肽,治疗1周后复查。结果治疗前心源性呼吸困难组血浆脑钠肽含量为(2 254±528)pg/L,明显高于肺源性呼吸困难组的(118±28)pg/L(P<0.05),也明显高于治疗后的(1 123±328)pg/L(P<0.05);肺源性呼吸困难组治疗前后血浆脑钠肽含量无明显差异(P>0.05)。结论根据血浆脑钠肽水平可快速、便捷、准确区分心源性与肺源性呼吸困难,对指导临床诊治具有较高的价值。     

神经干细胞与脑源性神经生长因子

神经干细胞对于损伤后的脑组织的修复、再生起着关键作用,脑源性神经生长因子对于干细胞的增殖分化起着重要作用。现有关于神经干细胞研究多为体外细胞研究,对于脑源性神经生长因子等因子对于内源性神经干细胞影响的研究较少。中医药诱导脑源性神经生长因子等其他因子增殖,进而影响神经干细胞增殖分化,可能成为一个新的研究切入点。     

脑源性神经营养因子:治疗阿尔采末病的新策略

阿尔采末病(又名阿尔茨海默病)的病因及发病机制复杂不清,目前脑源性神经营养因子在其发生、发展过程中的作用日益受到关注。本文综述了脑源性神经营养因子的生物学特点及作用,特别强调了脑源性神经营养因子在阿尔采术病病理生理学过程中的作用,旨在为后续研究该病的治疗药物提供新策略。     

脑源性晕厥的病因分析

目的探讨脑源性晕厥的病因。方法对186例晕厥患者进行各项实验室检查。特别是应用影像学检查方法。分析其基础疾病,实验室检查结果,分析26例诊断为脑源性晕厥患者的病因。结果26例患者均检出有不同程度的血管病变及颅内病变。无明显的致晕厥的心脏疾患。均可诊断为脑源性晕厥。结论部分晕厥为脑源性晕厥,对不明原因的晕厥患者除了行常规的实验室检查外,要给予血管影像学检查。     

脑源性神经营养因子的研究进展

近年来,科学研究发现神经营养因子是参与调控神经系统多种生理功能的一种蛋白质。其中,脑源性神经营养因子是一种在脑内合成的小分子二聚体蛋白质,对中枢系统神经元的生长、发育、分化、再生和修复具有重要作用。本文对脑源性神经营养因子的结构、功能、疾病相关性及临床应用前景进行了综述。     

Interleukins in atherosclerosis: molecular pathways and therapeutic potential

Interleukins are considered to be key players in the chronic vascular inflammatory response that is typical of atherosclerosis. Thus, the expression of proinflammatory interleukins and their receptors has been demonstrated in atheromatous tissue, and the serum levels of several of these cytokines have been found to be positively correlated with (coronary) arterial disease and its sequelae. In vitro studies have confirmed the involvement of various interleukins in pro-atherogenic processes, such as the up-regulation of adhesion molecules on endothelial cells, the activation of macrophages, and smooth muscle cell proliferation. Furthermore, studies in mice deficient or transgenic for specific interleukins have demonstrated that, whereas some interleukins are indeed intrinsically pro-atherogenic, others may have anti-atherogenic qualities. As the roles of individual interleukins in atherosclerosis are being uncovered, novel anti-atherogenic therapies, aimed at the modulation of interleukin function, are being explored. Several approaches have produced promising results in this respect, including the transfer of anti-inflammatory interleukins and the administration of decoys and antibodies directed against proinflammatory interleukins. The chronic nature of the disease and the generally pleiotropic effects of interleukins, however, will demand high specificity of action and/or effective targeting to prevent the emergence of adverse side effects with such treatments. This may prove to be the real challenge for the development of interleukin-based anti-atherosclerotic therapies, once the mediators and their targets have been delineated.     

白介素与骨关节炎

骨关节炎(OA)为老年人中的常见病,其病因及发病机制尚未完全明确。目前认为OA继发性滑膜炎的存在是OA慢性持续化的重要原因。在滑膜炎症释放的炎性介质中,白介素(IL)起了重要作用。本文介绍了IL的种类、信号传导、生物学功能以及IL-1、IL-6、IL-11、IL-12、IL-13等与OA的关系,及OA的抗IL治疗。     

Biological activities of interleukins and colony-stimulating factors

The complementary DNAs encoding interleukins (interleukins 1, 2, 3, 4, 5 and 6) and colony-stimulating factors (granulocyte-macrophage, granulocyte, and macrophage colony-stimulating factors) have been cloned. These DNA clones have allowed the large-scale production of recombinant forms of these cytokines and the extensive studies of their biological activities. These advances have led to a much better understanding of the role of these cytokines in regulation of immune responses and hematopoiesis, and have clarified that these cytokines have multiple effects on various types of cells.     

Suppression of immune response associated with functions of B-cells, Th1- and Th2-lymphocytes and interleukins produced by these cells, and pharmacological correction of these disturbances upon acute intoxication with methanol

Experiments on Wistar rats showed that acute poisoning with methanol (0.75 LD50) leads to the suppression of cellular and humoral immune responses and decreases the blood concentration of interleukins (IL-2, IL-4) with an increase in the IL-2/IL-4 ratio. These facts indicate that a decrease in Th2 lymphocyte activity is more pronounced in comparison to that of Th1 cells. The immunomodulators mielopide and polyoxidon administered in a daily dose of 10 mg/kg for 4 days upon acute poisoning with methanol virtually completely restore the cellular and humoral immune responses, the activity of natural killers, and the synthesis of interleukins.     

Low doses of Bisphenol A have pro-inflammatory and pro-oxidant effects,stimulate lipid peroxidation and increase the cardiotoxicity of Doxorubicin in cardiomyoblasts

Endocrine disrupters are strictly associated to cancer and several cardiovascular risk factors. Bisphenol A (BPA) is an endocrine disrupter commonly used in the manufacturing of plastics based on polycarbonate, polyvinyl chloride and resins. Our study aims to investigate whether BPA may cause pro-oxidative and pro-inflammatory effects on cardiomyoblasts, thus exacerbating the Doxorubicin (DOXO)-induced cardiotoxicity phenomena. We tested the metabolic effects of BPA at low doses analyzing its affections on the intracellular calcium uptake, oxidative stress, lipid peroxidation and production of nitric oxide and interleukins. Co-incubation of BPA and DOXO significantly reduced the cardiomyoblast viability, compared to only DOXO exposure cells. The mechanisms underlying these effects are based on the stimulation of the intracellular calcium accumulation and lipid peroxidation. Notably, BPA increase the production of pro-inflammatory interleukins involved in cardiovascular diseases as well as in DOXO-Induced cardiotoxicity phenomena. This study provides a rationale for translational studies in the field of cardio-oncology.     

Review article: biological activity markers in inflammatory bowel disease

BACKGROUND: Traditionally, inflammatory bowel disease activity is assessed by clinical activity indices that measure clinical symptoms and endoscopic indices that measure endoscopic inflammation. Biological markers are a non-invasive way of objectively measuring inflammation and can play an adjunctive or primary role in the assessment of disease activity. AIM: To review the data on biological markers for assessment of disease activity and prediction of relapse in inflammatory bowel disease. METHODS: To collect relevant articles, a PubMed search was performed from 1980 to 2006 using following search terms in combination: inflammatory bowel disease, biomarkers, inflammation, disease activity, relapse, acute phase reactants cytokines, interleukins, adhesion molecules, integrins, calprotectin and lactoferrin. RESULTS: Biological activity markers can be classified into serological, faecal and miscellaneous categories. Acute phase reactants levels correlate with disease activity and some can be used to help predict relapse. Cytokines and adhesion molecules are elevated in active disease inconsistently. Faecal markers are useful in assessment of disease activity and relapse. CONCLUSIONS: Acute phase reactants and faecal markers are useful to assess the disease activity in clinical practice. More data are required on cytokines and adhesion molecules. C-reactive protein, erythrocyte sedimentation rate, interleukins and faecal markers may be useful in predicting a relapse.     

Multiple mechanisms of cytokine action in neurodegenerative and psychiatric states: neurochemical and molecular substrates

Neuroinflammatory processes appear to play a fundamental role in the pathology associated with a number of neurodegenerative and psychiatric conditions. In this respect, the immunocompetent brain microglia and peripheral macrophages release a host of proinflammatory cytokines that not only modulate immunological processes but also influence neuronal functioning and even survival. For instance, alterations of the cytokines, tumor necrosis factor-alpha, as well as several of the interferons and interleukins have been associated with Parkinson's disease (PD) and clinical depression. Importantly, anti-inflammatory treatments that block these cytokines may impart protection against behavioural pathology and neuronal damage in animal models of PD and depression involving exposure to environmental toxins and stressors, respectively. The present review highlights the involvement of inflammatory cells and cytokines in depression and PD and explores some of the potential cellular and molecular mechanisms through which the immunotransmitters affect neuronal functioning. Attention is also devoted to the possibility that cytokines may sensitize neuroinflammatory pathways that, in turn, favour long-term pathology.     

6‐Ethyl‐N,N′‐bis(3‐hydroxyphenyl)[1,3,5]triazine‐2,4‐diamine (RS‐0466) Enhances the Protective Effect of Brain‐Derived Neurotrophic Factor on Amyloid β‐Induced Cytotoxicity in Cortical Neurones

Abstract: Amyloid β peptide in the senile plaques of patients with Alzheimer's disease is considered to be responsible for the pathology of Alzheimer's disease. We have previously reported that 6‐ethyl‐N,N′‐bis(3‐hydroxyphenyl)[1,3,5]triazine‐2,4‐diamine, RS‐0466, is capable of significantly inhibiting amyloid β‐induced cytotoxicity in HeLa cells. To determine various profiles of RS‐0466, we investigated whether RS‐0466 would enhance the neuroprotective effect of brain‐derived neurotrophic factor on amyloid β_1–42‐induced cytotoxicity in rat cortical neurones. Consistent with previous observations, brain‐derived neurotrophic factor ameliorated amyloid β_1–42‐induced cytotoxicity. Furthermore, co‐application of RS‐0466 enhanced the neuroprotective effect of brain‐derived neurotrophic factor. RS‐0466 also reversed amyloid β_1–42‐induced decrease of brain‐derived neurotrophic factor‐triggered phosphorylated Akt. These results raise the possibility that RS‐0466 or one of its derivatives has potential to enhance the neuroprotective effect of brain‐derived neurotrophic factor, and could serve as a therapeutic agent for patients with Alzheimer's disease.