核因子-κB与创伤的关系及其在法医病理学中的应用

损伤时间推断是法医病理学的一个研究热点和难点。核因子-κB(NF-κB)是一种核转录调节蛋白,参与多种炎性介质的转录和调控。近年来研究发现NF-κB与机体创伤后的反应密切相关,其在损伤后的时序性表达可望在法医病理学用于损伤时间推断。     

高压氧对急性移植物抗宿主病小鼠细胞因子表达的影响

目的:观察高压氧(HBO)对骨髓移植时急性移植物抗宿主病(aGVHD)小鼠脾组织中细胞因子表达的影响,探讨HBO抗aGVHD的作用机制.方法:应用直线加速器排空C57BL/6小鼠骨髓后,注入BALB/C小鼠骨髓与脾淋巴细胞的混合液,复制aGVHD模型.应用RT-PCR技术检测经HBO、环孢素A(CsA)、氨甲喋呤(MTX)处理后,小鼠脾组织中白细胞介素2(IL-2)、肿瘤坏死因子α(TNF-α)、白细胞介素4(IL-4)及白细胞介素10(IL-10)mRNA水平的变化.结果:HBO组小鼠11d的生存率明显高于异基因移植组及CsA MTX组;HBO组小鼠脾组织中TNF-α和IL-2mRNA相对含量显著低于异基因移植组(P＜0.05)、显著高于CsA MTX组;HBO组小鼠脾组织中IL-4和IL-10 mRNA相对含量显著高于异基因移植组及CsA MTX组(P＜0.05).结论:HBO可能通过调节促炎/抑炎细胞因子的分泌而发挥其明显的抗aGVHD作用.     

氧化苦参碱对哮喘小鼠抗炎作用的研究

目的：探讨氧化苦参碱治疗哮喘的抗炎作用机制及其对白细胞介素－4（IL－4mRNA)表达的影响。方法：建立小鼠哮喘模型，观察氧化苦参碱对哮喘小鼠支气管肺泡灌洗液中炎性细胞、肺组织病理的改变；应用半定量反转录－聚合酶链反应检测肺组织IL－4mRNA表达的变化。结果：氧化苦参碱可显著减轻哮喘小鼠气道及肺组织中哮酸性细胞的浸润，显著抑制哮喘小鼠肺组织中IL－4mRNA的表达水平。结论：氧化苦参碱对哮喘小鼠有明显的抗气道变应性炎症及抑制IL－4mRNA表达的作用。     

Potency variation of small-molecule chymase inhibitors across species

Chymases (EC 3.4.21.39) are mast cell serine proteinases that are variably expressed in different species and, in most cases, display either chymotryptic or elastolytic substrate specificity. Given that chymase inhibitors have emerged as potential therapeutic agents for treating various inflammatory, allergic, and cardiovascular disorders, it is important to understand interspecies differences of the enzymes as well as the behavior of inhibitors with them. We have expressed chymases from humans, macaques, dogs, sheep (MCP2 and MCP3), guinea pigs, and hamsters (HAM1 and HAM2) in baculovirus-infected insect cells. The enzymes were purified and characterized with kinetic constants by using chromogenic substrates. We evaluated in vitro the potency of five nonpeptide inhibitors, originally targeted against human chymase. The inhibitors exhibited remarkable cross-species variation of sensitivity, with the greatest potency observed against human and macaque chymases, with K_i values ranging from ∼0.4 to 72 nM. Compounds were 10-300-fold less potent, and in some instances ineffective, against chymases from the other species. The X-ray structure of one of the potent phosphinate inhibitors, JNJ-18054478, complexed with human chymase was solved at 1.8 Å resolution to further understand the binding mode. Subtle variations in the residues in the active site that are already known to influence chymase substrate specificity can also strongly affect the compound potency. The results are discussed in the context of selecting a suitable animal model to study compounds ultimately targeted for human chymase.     

Mucosal features and granulocyte–monocyte-apheresis in steroid-dependent/refractory ulcerative colitis

BACKGROUND: Mucosa-infiltrated granulocyte neutrophils are an early characteristic of inflammation and the main histological feature of active ulcerative colitis. Mucosal healing has recently been indicated as an important tool in the evaluation of response to treatment. While several studies have stressed the efficacy of granulocyte-monocyte-apheresis in inducing clinical remission in active ulcerative colitis, few data are available on mucosal features. AIM: Aim of this study was to assess the effects of granulocyte-monocyte-apheresis on clinical and mucosal features in patients with ulcerative colitis, dependent upon or refractory to steroids. MATERIAL AND METHODS: From April 2004 to April 2005, 12 patients (5 females, 7 males, mean age 49 years, range 33-71 years), with mild-moderate ulcerative colitis (six left colitis, six pancolitis) dependent/refractory upon steroids were enrolled. Each patient was treated for a 5-week period with five cycles of granulocyte-monocyte-apheresis. Patients were evaluated at baseline and 1 week after the last apheresis by means of Global Physician Assessment, quality of life features, laboratory tests (erythrocyte sedimentation rate, CRP, full blood count, faecal calprotectine), endoscopy and histology. RESULTS: At week 6 of follow-up, complete mucosal healing was observed in 3 out of 12 patients, partial mucosal healing in 8 patients and no change in 1 patient. Clinical response was complete in 8 out of 12 patients. CONCLUSIONS: These data suggest that granulocyte-monocyte-apheresis induces an improvement both in clinical and mucosal lesions in steroid-dependent/refractory ulcerative colitis. Of note, the reduction in granulocyte infiltration and the improvement in mucosal lesions are accompanied by a reduction in faecal calprotectine.     

炎症性肠病危险因素的流行病学调查研究

目的通过病例调查，筛选IBD的危险因素。方法采用问卷方式，对72例确诊IBD患者及72例配对的健康个体调查，对结果进行COX回归分析，筛选出IBD的致病危险因素。结果COX回归分析提示紧张度、牛奶和油炸食品在IBD致病因素中具有统计学意义。结论紧张度、牛奶和油炸食品可能是IBD的致病危险因素。     

对大肠癌术后早期炎性肠梗阻诊治的探讨

目的：探讨大肠癌术后早期炎性肠梗阻的特点及治疗方法；方法：分析10例大肠癌术后出现早期炎性肠梗阻的临床表现并进行综合保守治疗；结果：10例患者保守治疗全部成功；结论：术后早期炎性肠梗阻是一种非细菌性炎性肠梗阻，以发生在术后早期，腹胀、呕吐明显，腹痛轻或无为主要临床特点，治疗应采用保守治疗。     

转录因子Egr-1在失血性休克复苏后肝脏损伤中的作用

目的研究转录因子Egr-1在失血性休克复苏（HS/R）后肝脏损伤中的作用.方法利用Egr-1野生型（WT）和基因封闭型（KO）小鼠复制失血性休克复苏模型.取肝组织,RT-PCR法测定肝组织中TNF-α、IL-6、G-CSF、ICAM-1 mRNA的表达变化.通过检测肝组织中MPO的含量、血清ALT水平和组织学检查,评估肝脏炎症细胞浸润和损伤程度.结果失血性休克2.5 h＋复苏4 h后,Egr-1 KO小鼠肝组织中TNF-α、IL-6、G-CSF、ICAM-1 mRNA的表达水平明显低于Egr-1WT组;Egr-1 KO组失血性休克复苏后肝组织炎性浸润和损伤程度减轻,表现为血清ALT水平低,肝组织中MPO含量低,病理损伤轻.结论本实验结果表明转录因子Egr-1参与了失血性休克复苏后肝脏炎症反应基因表达的调节,在失血性休克复苏后的肝脏损伤中起一定的作用.     

慢性髓性白血病细胞来源的树突状细胞大容量诱导及其功能的实验研究

目的　探索大容量诱导慢性髓性白血病 (CML)细胞来源的树突状细胞 (DCs)的适宜方法 ;研究CML DCs刺激自体T淋巴细胞增殖并分泌γ 干扰素 (IFN γ)的能力。方法　用CS 30 0 0 plus血细胞分离机采集初诊CML病人的外周血单个核细胞 (PBMNCs) ;单采的CML PBMNCS转入组织培养袋 ,加入重组人粒 巨细胞集落刺激因子 (rhGM CSF)和重组人白介素 4 (rhIL 4 ) ,培养诱导 7d ;在诱导前后 ,用流式细胞仪分别检测细胞表面HLA DR、CD1a、CD80和CD86的表达水平 ;用3 H TdR掺入法检测CML DCs和CML PBMNCs刺激自体和异体T细胞增殖的能力 ;用ELISA法检测在自体混合淋巴细胞培养 (MLR)时T细胞分泌的IFN γ浓度。结果　用血细胞分离机收集的CML PBMNCs ,在组织培养袋内经细胞因子培养诱导 ,HLA DR、CD1a、CD80、CD86的表达均有明显上调 ,细胞形态也表现典型的DC特征 ;CML DCs能显著刺激自体和异体T细胞增殖 ,而CML PBM NCs仅能刺激异体T细胞的增殖 ,刺激自体T细胞增殖的能力很弱 ;刺激自体T细胞增殖时分泌的IFN γ浓度 ,CML DCs组为 (877± 2 14 )pg/mL ;CML BPMNCs组仅为 (14± 1.7) pg/mL。 结论　单采的CML PBMNCs转入组织培养袋 ,加入rhGM CSF和rhIL 4 ,可收获大容量的CML DCs;CML DCs在体外具有显著刺激自体T细胞增殖     

大气颗粒物健康效应生物学机制研究进展

大量流行病学研究发现，大气颗粒物的污染水平与心肺系统疾病的超额发病、死亡存在密切关联，但其毒理学机制尚未阐明。本文对近年来大气颗粒物毒理学研究进行综述，包括大气颗粒物对呼吸系统、心血管系统及神经系统的毒性作用，并对氧化应激损伤、细胞钙稳态失衡及激活关键转录因子等分子毒理学机制进行了初步的阐述。