大黄对肠源性感染早期肺损伤大鼠内毒素的影响

目的：观察大黄治疗大鼠肠源性肺损伤时内毒素变化。方法：采用大鼠盲肠结扎并穿孔(CLP)造成腹腔感染，每日在麻醉下经胃管灌注大黄1次。分别在术前及术后24，48，72，96，120 h处死1组大鼠，检测肺毛细血管通透性、支气管肺泡灌洗液(BALF)的中性粒细胞百分率,分析血浆、肺组织和BALF的内毒素水平。结果：肺毛细血管通透性、BALF的中性粒细胞百分率及血浆、肺组织和BALF的内毒素含量逐渐增加，时间越长作用越明显。治疗组比感染组增加较慢、幅度较小。结论：大黄可阻止肺组织的内毒素含量和中性粒细胞数量的增加，减轻肺损伤。     

肾损伤因子在肾脏疾病中的应用

中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-assocliated lipocalin,NGAL)是脂质运载蛋白家族的新成员,存在于人类的一些正常组织中.近年来研究表明NGAL与肾脏疾病有一定的关系.NGAL是急性肾损伤的早期标志物,与传统的急性肾功能不全(ARF)实验室指标血肌酐相比,NGAL可以更早且准确地诊断ARF;NGAL在慢性肾脏疾病中也发挥着一定的功能,可体现慢性肾脏疾病的进展程度及治疗效果;在终末肾病中,NGAL可以作为血液透析以及疗效的指标.     

西维来司钠对脑损伤继发吸入性肺损伤大鼠的影响研究

目的:探讨西维来司钠(Sivelestat sodiom)雾化吸入对脑损伤继发肺损伤大鼠的影响,从炎性反应角度探讨其作用机制.方法:SD大鼠60只,随机分为6组,正常组(A),误吸组(B),脑损伤误吸组(C),生理盐水雾化吸入组(D),地塞米松雾化吸入组(E),西维来司钠雾化吸入组(F),每组10只,用酶联免疫吸附(Enzyme-linked immunosorbent assay,ELISA)法测定支气管肺泡灌洗液(Bronchoalveolar lavage fluid,BALF)的中性粒细胞弹性蛋白酶(Neutrophil elastase,NE)和白介素-8(Interleukin-8,IL-8)含量,免疫透射比浊法测定BALF中白蛋白浓度;光镜观察肺组织病理改变.结果:F组肺组织形态学改善最明显,其次为E组;E、F组大鼠BALF中NE低于B、C、D组(P＜0.05),F组最明显;E、F组大鼠BALF中IL-8含量均低于C、D组(P＜0.05),但E、F2组间差异无统计学意义(P＞0.05).结论:西维来司钠雾化吸入对脑损伤继发吸入性肺损伤大鼠肺组织的改善作用优于地塞米松,其作用机制可能与抑制NE的产生和活性,减轻NE对肺组织的直接损伤作用和抑制肺内炎性网络循环反应导致的肺组织损伤有关.     

子痫前期患者外周血中性粒细胞凋亡及Mcl-1、caspase-3表达的研究

目的:研究子痫前期患者外周血中性粒细胞凋亡情况及其机制。方法:选取2003年10月~2004年9月在我院产科住院的子痫前期患者、正常妊娠孕妇各20例,分离外周血中性粒细胞并体外培养24 h,流式细胞术检测凋亡率,RT-PCR检测Mcl-1 mRNA的表达,免疫印迹法检测caspase-3蛋白的表达。结果:子痫前期组外周血中性粒细胞凋亡率(16.51%±3.84%)明显低于正常妊娠组(30.62%±6.27%),子痫前期组中性粒细胞Mcl-1 mRNA表达增加,caspase-3蛋白活化降低。结论:子痫前期患者外周血中性粒细胞存在凋亡延迟,Mcl-1表达上调和caspase-3活化抑制可能是凋亡延迟的重要机制。     

骨髓增殖性肿瘤患者NGAL、VEGF、PC及PS表达水平及意义研究

目的观察骨髓增殖性肿瘤(MPN)患者中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、血管内皮生长因子(VEGF)、血浆蛋白C(PC)及血浆蛋白S(PS)表达水平,并分析其临床意义。方法回顾性选取2019年1月至2021年8月在沧州市中心医院初诊MPN患者40例、MPN治疗后患者40例,以及健康体检者40例为研究对象,分别作为初诊组、治疗后组、对照组。观察3组研究对象、不同临床特征MPN患者的NGAL、VEGF、PC及PS表达水平,分析影响MPN患者的NGAL、VEGF、PC及PS表达水平的因素。结果初诊组、治疗后组的NGAL[(18.34±2.11)、(10.49±1.87)ng/mL]、VEGF[(239.29±10.45)、(151.34±9.13) pg/mL]水平均显著高于对照组[(2.37±0.45) ng/mL、(78.66±8.35) pg/mL],初诊组、治疗后组的PC[(1 794.35±142.49)、(2 918.21±85.35) ng/mL]、PS[(43 424.64±102.41)、(63 467.47±125.48) ng/mL]水平均显著低于对照组[(3...     

阿托伐他汀对大鼠脑缺血再灌注后梗死灶周围中性粒细胞浸润和核转录因子-κB表达水平的影响

目的 观察阿托伐他汀对大鼠脑缺血再灌注后梗死灶周围中性粒细胞浸润以及核转录因子-κB表达水平的影响.方法 采用常规尼龙线栓法制备SD大鼠脑缺血再灌注模型,并将大鼠随机分为假手术组、大脑中动脉阻断再灌注(Middle cerebral artery occlusion/reperfusion,MCAO/R)(对照)组和M...     

轻、中度持续性哮喘患者气道黏膜病理变化及与嗜中性粒细胞的关系

目的：研究轻、中度持续性哮喘患者气道粘膜病理变化与嗜中性粒细胞的关系及其机制。方法：选择12例间歇哮喘患者（A组）、16例轻度或中度持续性哮喘患者（B组）、14例早期周围型肺癌患者（C组,对照组）,经纤维支气管镜进行支气管肺泡灌洗和气道黏膜活检,做HE和免疫组化染色、炎性细胞计数及介质测定。结果：A、B、C组支气管肺泡灌洗液（BALF）中嗜酸性粒细胞（Eos）计数A、B组显著高于C组（P＜0.05）;嗜中性粒细胞计数B组显著高于A、C组（P＜0.05）;嗜酸粒细胞性阳离子蛋白（ECP）含量A、B组显著高于C组（P＜0.05）;嗜中性粒细胞髓过氧化物酶（MPO）含量B组显著高于A、C组（P＜0.05）;白细胞介素-8（IL-8）含量B组显著高于A、C组（P＜0.05）。A、B组气道上皮均有不同程度的脱落、变薄,基底膜增厚;B组的气道黏膜下层MPO阳性细胞计数显著高于A组（P＜0.05）。结论：嗜中性粒细胞与Eos共同参与了轻、中度持续性哮喘患者气道黏膜炎症反应,嗜中性粒细胞可能在其中发挥了更重要的作用。     

Glycine induces enhancement of bactericidal activity of neutrophils

Severe bacterial infections are frequently accompanied by depressed neutrophil functions. Thus, agents that increase the microbicidal activity of neutrophils could add to a direct antimicrobial therapy. Lysophosphatidylcholine augments neutrophil bactericidal activity via the glycine (Gly)/glycine receptor (GlyR) α2/TRPM2/p38 mitogen-activated protein kinase (MAPK) pathway. However, the direct effect of glycine on neutrophil bactericidal activity was not reported. In this study, the effect of glycine on neutrophil bactericidal activity was examined. Glycine augmented bactericidal activity of human neutrophils (EC₅₀ = 238 μM) in a strychnine (a GlyR antagonist)-sensitive manner. Glycine augmented bacterial clearance in mice, which was also blocked by strychnine (0.4 mg/kg, s.c.). Glycine enhanced NADPH oxidase-mediated reactive oxygen species (ROS) production and TRPM2-mediated [Ca²⁺]_i increase in neutrophils that had taken up E. coli. Glycine augmented Lucifer yellow uptake (fluid-phase pinocytosis) and azurophil granule-phagosome fusion in neutrophils that had taken up E. coli in an SB203580 (a p38 MAPK inhibitor)-sensitive manner. These findings indicate that glycine augments neutrophil microbicidal activity by enhancing azurophil granule-phagosome fusion via the GlyRα2/ROS/calcium/p38 MAPK pathway. We suggest that glycine could be a useful agent for increasing neutrophil bacterial clearance.     

Enhanced tumor homing of pathogen-mimicking liposomes driven by R848 stimulation: A new platform for synergistic oncology therapy

Although multifarious tumor-targeting modifications of nanoparticulate systems have been attempted in joint efforts by our predecessors, it remains challenging for nanomedicine to traverse physiological barriers involving blood vessels, tissues, and cell barriers to thereafter demonstrate excellent antitumor effects. To further overcome these inherent obstacles, we designed and prepared mycoplasma membrane (MM)-fused liposomes (LPs) with the goal of employing circulating neutrophils with the advantage of inflammatory cytokine-guided autonomous tumor localization to transport nanoparticles. We also utilized in vivo neutrophil activation induced by the liposomal form of the immune activator resiquimod (LPs-R848). Fused LPs preparations retained mycoplasma pathogen characteristics and achieved rapid recognition and endocytosis by activated neutrophils stimulated by LPs-R848. The enhanced neutrophil infiltration in homing of the inflammatory tumor microenvironment allowed more nanoparticles to be delivered into solid tumors. Facilitated by the formation of neutrophil extracellular traps (NETs), podophyllotoxin (POD)-loaded MM-fused LPs (MM-LPs-POD) were concomitantly released from neutrophils and subsequently engulfed by tumor cells during inflammation. MM-LPs-POD displayed superior suppression efficacy of tumor growth and lung metastasis in a 4T1 breast tumor model. Overall, such a strategy of pathogen-mimicking nanoparticles hijacking neutrophils in situ combined with enhanced neutrophil infiltration indeed elevates the potential of chemotherapeutics for tumor targeting therapy.     

Prmt1 upregulated by Hdc deficiency aggravates acute myocardial infarction via NETosis

Neutrophils are mobilized and recruited to the injured heart after myocardial infarction, and neutrophil count has been clinically implicated to be associated with coronary disease severity. Histidine decarboxylase (HDC) has been implicated in regulating reactive oxidative species (ROS) and the differentiation of myeloid cells. However, the effect of HDC on neutrophils after myocardial infarction remains unclear. Here, we found that neutrophils were disorderly recruited into the ischemic injured area of the myocardium of Hdc deficiency (Hdc^?/?) mice. Moreover, Hdc deficiency led to attenuated adhesion but enhanced migration and augmented ROS/neutrophil extracellular traps (NETs) production in neutrophils. Hdc^?/? mouse-derived NETs promoted cardiomyocyte death and cardiac fibroblast proliferation/migration. Furthermore, protein arginine methyltransferase 1 (PRMT1) was increased in Hdc^?/? mouse-derived neutrophils but decreased with exogenous histamine treatment. Its expression could be rescued by blocking histamine receptor 1 (H1R), inhibiting ATP synthesis or reducing SWItch/sucrose non fermentable (SWI/SNF) chromatin remodeling complex. Accordingly, histamine or MS023 treatment could decrease ROS and NETs ex vivo, and ameliorated cardiac function and fibrosis, along with the reduced NETs in plasma in vivo. Together, our findings unveil the role of HDC in NETosis by histamine–H1R–ATP–SWI/SNF–PRMT1–ROS signaling and provide new biomarkers and targets for identifying and tuning the detrimental immune state in cardiovascular disease.