缺血预适应对大鼠保留肾单位手术中缺血再灌注损伤的保护作用及其机制研究

目的 探讨缺血预适应(IPC)动员肾祖细胞(RPC)归巢在保留肾单位手术(NSS)中对肾脏缺血再灌注损伤(IRI)的保护作用及其发生机制。方法 选取2~3月龄、体质量250~300 g的雄性SD大鼠54只,建立切除右肾的单肾模型后采用数字表法随机分为3组,每组18只:假手术组(Sham组,无血管夹闭),NSS组(肾动脉夹闭45 min后行NSS),IPC组(先进行肾动脉夹闭15 min,再灌注10 min预处理,再行NSS)。分别在术后12、24、72 h每组各取出6只大鼠,收集血液及肾组织标本,之后采用颈椎脱臼法处死大鼠。观察项目:(1)检测血肌酐(SCr)、尿素氮(BUN);(2)组织病理学检查及肾小管损伤评分;(3)在24 h观察IPC对肾组织中RPC数量的影响,以及IPC对基质细胞衍生因子(SDF-1)、受体CXCR7表达水平的影响。结果 (1)术后12、24、72 h 时3组大鼠SCr和BUN值比较, IPC组分别为(65.0±10.78)、(91.5±15.12)、(52.6±11.68)μmol/L和(14.78±2.77)、(18.31±4.99)、(9.41±2.73)mmol/L,NSS组分别为(80.5±12.63)、(116.9±14.32)、(83.7±11.43)μmol/L和(18.58±4.18)、(28.86±5.64)、(19.49±3.83)mmol/L, Sham组分别为(41.5±7.36)、(39.7±7.55)、(42.7±7.15)μmol/L和(7.72±1.75)、(7.40±1.98)、(6.83±2.09)mmol/L;除72 h时IPC组与Sham组SCr和BUN值比较差异无统计学意义(P＞0.05)外,在12 h和24 h,IPC组均高于Sham组、低于NSS组,差异均有统计学意义(P值均＜0.05)。(2)术后12、24、72 h肾小管损伤评分IPC组和NSS组均高于Sham组,术后12、24 h IPC组较NSS组肾小管损伤评分低,差异均有统计学意义(P值均＜0.05)。(3)术后24 h,IPC组和NSS组大鼠肾组织中RPC数量明显增加、SDF-1和CXCR7表达显著升高,差异均有统计学意义(P值均＜0.05)。结论 IPC可促进RPC归巢,缓解NSS中IRI损伤程度,保护肾功能,SDF-1/CXCR7轴可能在这一动员过程中发挥了重要作用。     

CXCR4与肿瘤的发生和发展

趋化因子受体-4（chemokinereceptor-4,CXCR4）属趋化因子家族,为G蛋白偶联的7次跨膜受体蛋白,基质细胞衍生因子-12是该受体的唯一配体。目前发现CXCR4在23种不同类型肿瘤中均有表达,与肿瘤细胞的增殖、侵袭、转移及预后密切相关,针对CXCR4靶向治疗可望成为肿瘤基因治疗研究的新热点。     

Elevation of serum CXCL16 level correlates well with atherosclerotic ischemic stroke

Introduction

Currently there are no reliable biological markers for ischemic stroke. The novel chemokine CXCL16 is known to be involved in the development of atherosclerosis. Nevertheless, the real role of CXCL16 in atherosclerotic disorders remains uncertain. The goal of our study was to investigate the associations between serum-soluble CXCL16 level and atherosclerotic ischemic stroke, including large artery atherosclerosis (LAA) and small artery occlusion (SAO) subtypes, and to explore whether elevation in CXCL16 levels is correlated with the severity of large arterial stenosis.

Material and methods

The study recruited 227 subjects, including 74 controls and 153 consecutive patients with acute ischemic stroke from atherosclerosis of the carotid artery. The etiology of the acute ischemic strokes was classified into LAA (n = 86) subtype and SAO (n = 67) subtype according to the TOAST criteria, and the severity of carotid artery stenosis was assessed by the NASCET criteria. Serum-soluble CXCL16 concentration was measured by enzyme-linked immunosorbent assay.

Results

Serum CXCL16 concentrations were significantly increased in both LAA (2.36 ng/ml) and SAO subtypes (2.13 ng/ml) when compared to that of the controls (2.04 ng/ml, p < 0.01 and p < 0.05, respectively), and it was significantly elevated in LAA subtype than in SAO subtype (p < 0.05). However, significant differences in CXCL16 levels between the high-grade stenosis group (2.36 ng/ml) and moderate-grade stenosis group (2.24 ng/ml) of LAA subtype were not found (p > 0.05). A correlation of serum levels of CXCL16 with serum levels of hs-CRP, fibrinogen and lipid parameters was not observed (p > 0.05).

Conclusions

Increased serum level of soluble CXCL16 was independently associated with atherosclerotic ischemic stroke, particularly LAA subtype.     

Hyperbaric oxygen preconditioning promotes neovascularization of transplanted skin flaps in rats

To determine whether Hyperbaric oxygen preconditioning (HBO-PC) promotes neovascularization by increasing Stromal cell derived factor-1 (SDF-1) and CXC chemokine receptor 4 (CXCR4) in transplanted skin flaps of rats. The epigastric pedicle skin flap was established in a rat model. Rats were randomly assigned to the following five groups: 1) sham-operated group (SH); 2) ischemia followed by reperfusion 3 days postoperatively group (IR3d); 3) ischemia followed by reperfusion 5 days postoperatively group (IR5d); 4) hyperbaric oxygen preconditioning and ischemia followed by reperfusion 3 days postoperatively group (HBO-PC3d); and 5) hyperbaric oxygen preconditioning and ischemia followed by reperfusion 5 days postoperatively group(HBO-PC5d). For the groups receiving HBO-PC, animals underwent 1 hour of HBO at 2.0 ATA in 100% O₂ twice per day for 3 days consecutively prior to surgery. After perfusion, Laser Doppler perfusion imaging (LDPI) was performed, and skin flap tissue samples were harvested for histological evaluation and western blot analysis. Perfusion was significantly improved in the HBO-PC groups compared with the IR groups on postoperative 3 and 5. Microvessel density (MVD) was significantly increased by HBO-PC compared with IR groups postoperatively. Western blot analysis revealed that SDF-1 and CXCR4 expression in the HBO-PC groups was significantly increased compared with IR groups. HBO-PC promoted neovascularization via increasing expression levels of SDF-1 and CXCR4 in transplanted skin flaps of rats.     

趋化因子及其受体在非霍奇金淋巴瘤中的研究进展

趋化因子及其受体在正常免疫细胞的发育及迁移中发挥着重要作用。近年来相关研究显示,非霍奇金淋巴瘤细胞表面趋化因子受体表达上调,调控着疾病的发生与转移,影响患者预后。针对趋化因子受体的靶向药物在逐步研究并应用于造血干细胞动员及抗淋巴瘤的治疗,新的非典型趋化因子家族被逐渐发现并展现出一定的抗淋巴瘤作用,有潜力成为新的淋巴瘤治疗手段。本文就主要的趋化因子及其受体在非霍奇金淋巴瘤中的研究进展作一综述。     

血清YKL-40、CCL18和hs-cTnT预测急性心肌梗死患者心血管不良事件的临床价值

目的 观察血清甲壳质酶蛋白（YKL） 40、趋化因子配体18（CCL18）和高敏心肌肌钙蛋白（hs cTnT）在预测急性心肌梗死患者心血管不良事件中的临床价值。方法 选择2016年1月至2018年6月在我院诊治的急性心肌梗死患者118例。采用酶联免疫吸附试验检测血清YKL 40、CCL18和hs cTnT。观察急性心肌梗死患者血清YKL 40、CCL18和hs cTnT水平与冠状动脉狭窄程度和发生主要不良事件的关系。结果 急性心肌梗死患者血清YKL 40、CCL18和hs cTnT水平随着Gensini评分升高而升高,事件组血清YKL 40、CCL18和hs cTnT水平明显高于非事件组（P<0.01）。急性心肌梗死患者血清YKL 40、CCL18和hs cTnT水平是发生主要不良事件的独立危险因素,在预测主要不良事件方面具有较高的灵敏度和特异度,联合检测对预测急性心肌梗死不良事件具有更高的诊断效能,其灵敏度为89.2%,特异度为86.4%,其曲线下面积（ACU）明显高于YKL 40（Z=3.397,P<0.01）、CCL18（Z=2.796,P<0.01）和hs cTnT（Z=2.613,P<0.01）。结论 血清YKL 40、CCL18和hs cTnT是反映急性心肌梗死严重程度的指标,对急性心肌梗死不良事件的发生具有预测作用。     

Evaluation of WO2012080456 and WO2012080457; Boheringer Ingleheim's first CXCR2 antagonists

Two applications claim CXCR2 receptor antagonists respectively incorporating arylcarbonyl and arylsulfonyl substituted 2-hydroxyaniline scaffolds. The first application claims both N-aryl,N′-aryl urea and squaramide derivatives, the second focuses on squaramide derivatives. Several examples of the latter scaffold with nanomolar affinity are provided and indicate an alternative modification of the squaramide scaffold that has been explored extensively by other groups.     

Chemokine CCR3 antagonists

Because CC chemokine receptor 3 (CCR3) expression is confined to eosinophils, and such leukocytes play an important role in allergic disorders, identification of CCR3 antagonists represents a logical approach to identifying new treatments for eosinophil-associated inflammatory disorders such as asthma. CCR3 is also expressed on basophils, mast cells, airway epithelial cells and a subpopulation of T-helper 2 lymphocytes, which has increased interest in its possible role in allergy. Substantial research efforts by a number of drug companies have been directed at the development of small molecule CCR3 antagonists. This review encompasses patent applications pertaining to disclosures of CCR3 antagonists.     

Tissue factor antisense deoxyoligonucleotide prevents monocrotaline/LPS hepatotoxicity in mice

Tissue factor (TF) is a membranous glycoprotein that functions as a receptor for coagulation factor VII/VIIa and activates the coagulation system when blood vessels or tissues are damaged. TF was upregulated in our monocrotaline (MCT)/lipopolysaccharide (LPS) hepatotoxicity model. We tested the hypothesis that TF‐dependent fibrin deposition and lipid peroxidation in the form of oxidized low‐density‐lipoprotein (ox‐LDL) accumulation contribute to liver inflammation induced by MCT/LPS in mice. In the present study, we blocked TF using antisense oligodeoxynucleotides against mouse TF (TF‐ASO). TF‐ASO (5.6 mg kg^?1) was given i.v. to ND4 male mice 30 min after administration of MCT (200 mg kg^?1) p.o. followed after 3.5 h by LPS i.p. (6 mg kg^?1). Blood alanine aminotransferase (ALT), TF, ox‐LDL, platelets, hematocrit and keratinocyte‐derived chemokine (KC) levels were evaluated in different treatment groups. Fibrin deposition and ox‐LDL accumulation were also analyzed in the liver sections using immunofluorescent staining. The results showed that TF‐ASO significantly restored blood ALT, hematocrit and KC levels, distorted after MCT/LPS co‐treatment, as well as preventing the accumulation of ox‐LDL and the deposition of fibrin in the liver tissues, and thereby inhibited liver injury caused by MCT/LPS. In a separate experiment, TF‐ASO administration significantly prolonged animal survival. The current study demonstrates that TF is associated with MCT/LPS‐induced liver injury. Administration of TF‐ASO successfully prevented this type of liver injury. Copyright © 2012 John Wiley & Sons, Ltd.