Dual effect of chemokine CCL7/MCP-3 in the development of renal tubulointerstitial fibrosis

Most end-stage renal disease kidneys display accumulation of extracellular matrix (ECM) in the renal tubular compartment (tubular interstitial fibrosis – TIF) which is strongly correlated with the future loss of renal function. Although inflammation is a key event in the development of TIF, it can also have a beneficial anti-fibrotic role depending in particular on the stage of the pathology. Chemokines play an important role in monocyte extravasation in the inflammatory process. CCL2 has already been shown to be involved in the development of TIF but CCL7, a close relative of CCL2 and able to bind to similar receptors, has not been studied in renal disease. We therefore studied chemokine CCL7 in a model of unilateral ureteral obstruction (UUO)-induced TIF. We observed that the role of CCL7 differs depending on the stage of the pathology. In early stages (0–8 days), CCL7 deficient (CCL7-KO) mice displayed attenuated TIF potentially involving two mechanisms: an early (0–3 days) decrease of inflammatory cell infiltration followed (3–8 days) by a decrease in tubular ECM production independent of inflammation. In contrast, during later stages of obstruction (10–14 days), CCL7-KO mice displayed increased TIF which was again associated with reduced inflammation. Interestingly, the switch between this anti- to profibrotic effect was accompanied by an increased influx of immunosuppressive regulatory T cells. In conclusion, these results highlight for the first time a dual role for CCL7 in the development of renal TIF, deleterious in early stages but beneficial during later stages.     

炎症和氧化应激对内皮祖细胞动员及其功能的影响

内皮祖细胞对于维持血管内皮完整性和血管稳态具有重要作用.增强EPC的数量和功能可使心血管疾病患者获益.炎症、氧化应激对内皮祖细胞动员及其功能发挥具有重要影响,本文着重综述炎症和氧化应激对内皮祖细胞动员的调控,并探讨增进内皮祖细胞数量和功能的相关治疗策略.     

表没食子儿茶素没食子酸酯对高脂饮食大鼠脂肪组织TNF-α表达的影响及意义

目的 探讨表没食子儿茶素没食子酸酯（EGCG）对高脂饮食大鼠脂肪组织中肿瘤坏死因子-α（TNF-α）表达的影响及其与胰岛素敏感性的相关性.方法 将30只SPF级雄性SD大鼠随机分为正常饮食组（ND组,n=10）和高脂饮食组（HFD组,n=20）.喂养16w,当两组大鼠体质量出现显著差异后（P〈0.05）,将HFD组按随机区组原则分为单纯高脂组（HFD组,n=10）和EGCG干预组（HFD＋0.32%EGCG,EGCG组,n=10）.干预16w.留取血清及附睾周脂肪组织.检测每组大鼠空腹血糖（FBG）、胰岛素水平（FINS）及游离脂肪酸（FFAs）,并计算胰岛素抵抗指数（HOMA-IR）;应用Real-time PCR及Western blot方法检测附睾周脂肪组织中TNF-α表达水平.结果 （1）与HFD组相比,EGCG组FINS水平显著下降[分别为（13.83±0.79）mIU/l vs.（31.71±3.61）mIU/l,P〈0.05];HOMA-IR值下降[分别为（3.36±0.31） vs.（7.59±0.99）,P〈0.05];FFAs值亦明显下降[分别为（0.38±0.08）mmol/l vs.（0.81±0.11）mmol/l,P〈0.05];三组大鼠FBG水平无明显统计学差异（P〉0.05）.（2）与ND组相比,HFD组脂肪组织中TNF-αmRNA水平显著升高[分别为（0.0033±0.00070）vs.（0.0010±0.00008）,P〈0.01];而EGCG组较HFD组则明显下降[分别为（0.0018±0.00037）vs.（0.0033±0.00070）,P〈0.05];同时,EGCG组TNF-α蛋白表达量低于HFD组[分别为（0.42±0.09）vs.（0.67±0.09）,P〈0.05];（3）EGCG组与ND组无明显差异（P〉0.05）.结论 EGCG改善高脂饮食大鼠胰岛素敏感性可能与减轻脂肪组织TNF-α介导的炎症状态相关.     

维生素D3对自发性高血压大鼠靶器官炎症的影响

目的探索维生素D3与高血压和炎症的关系。方法自发性高血压大鼠20只,随机分为对照组和实验组,各10只。实验组大鼠腹腔注射维生索D3制剂3μg／kg（溶于20％丙二醇0．5mL中）,每周2次;对照组仅腹腔注射丙二醇0．5mL,两组均干预12周。实验过程中监测大鼠血压变化。干预前后,酶联免疫法检测血清25（OH）D3、钙、白细胞介素-6（IL-6）、基质金属蛋白酶-9（MMP-9）的浓度;计算肾脏-体重比和心脏-体重比;HE染色观察两组大鼠肾脏、心脏、主动脉、小动脉组织病理改变。结果实验组和对照组在干预前血压无差异显著性（P〉0．05）;干预后,实验组和对照组大鼠平均收缩压分别为（157±9）mmHg和（173±8）mmHg（P〈0．05）。实验组的血清25（OH）D3、血钙水平比对照组高（P〈0．05）,IL-6、MMP-9水平实验组比对照组低（P〈0．05）。实验组的心脏-体重比小于对照组（P〈0．05）。实验组的肾脏、心脏和小动脉高血压、炎性损害明显轻于对照组。结论规律的维生素D3用药能够抑制炎症因子IL-6、MMP-9的产生,抑制机体炎症反应,调节控制血压。     

Curcumin ameliorates TNF-α-induced ICAM-1 expression and subsequent THP-1 adhesiveness via the induction of heme oxygenase-1 in the HaCaT cells

Adhesion molecules such as ICAM-1 are important in the infiltration of leukocytes into the site of inflammation. In this study, we investigated the inhibitory effects of curcumin on ICAM-1 expression and monocyte adhesiveness as well as its underlying action mechanism in the TNF-α-stimulated keratinocytes. Curcumin induced expression of heme oxygenase-1 (HO-1) in the human keratinocyte cell line HaCaT. In addition, curcumin induced Nrf2 activation in dose- and time-dependent manners in the HaCaT cells. Curcumin suppressed TNF-α- induced ICAM-1 expression and subsequent monocyte adhesion, which were reversed by the addition of tin protoporphyrin IX (SnPP), a specific inhibitor of HO-1, or HO-1 knockdown using siRNA. Furthermore, Nrf2 knockdown using siRNA reversed the inhibitory effect of curcumin on the TNF-α-induced ICAM-1 expression and adhesion of monocytes to keratinocytes. These results suggest that curcumin may exert its anti-inflammatory activity by suppressing the TNF-α-induced ICAM-1 expression and subsequent monocyte adhesion via expression of HO-1 in the keratinocytes. [BMB Reports 2013;46(8): 410-415]     

中性粒细胞胞外诱捕网和血栓形成的研究进展

中性粒细胞胞外诱捕网是由DNA骨架、组蛋白、颗粒成分以及胞浆蛋白组成的网状物,它通过捕获致病微生物,抑制其扩散、灭活毒力因子以及清除病原体来发挥抗菌活性,中性粒细胞这种与其经典的趋化、吞噬作用不同的胞外杀菌方式发挥着重要的固有免疫应答作用。然而,中性粒细胞胞外诱捕网的产生是一把双刃剑。近年来有研究表明它可以导致凝血异常、刺激血栓形成并为其提供支架,但这一过程的机制并不十分清楚,可能与中性粒细胞胞外诱捕网的促凝活性以及凝血级联反应的激活有关。本文将就中性粒细胞胞外诱捕网及其与血栓形成之间关系的研究进展做一综述。     

Label‐free analysis of human cerebrospinal fluid addressing various normalization strategies and revealing protein groups affected by multiple sclerosis

The aims of the study were to: (i) identify differentially regulated proteins in cerebrospinal fluid (CSF) between multiple sclerosis (MS) patients and non‐MS controls; (ii) examine the effect of matching the CSF samples on either total protein amount or volume, and compare four protein normalization strategies for CSF protein quantification. CSF from MS patients (n = 37) and controls (n = 64), consisting of other noninflammatory neurological diseases (n = 50) and non neurological spinal anesthetic subjects (n = 14), were analyzed using label‐free proteomics, quantifying almost 800 proteins. In total, 122 proteins were significantly regulated (p < 0.05), where 77 proteins had p‐value <0.01 or AUC value >0.75. Hierarchical clustering indicated that there were two main groups of MS patients, those with increased levels of inflammatory response proteins and decreased levels of proteins involved in neuronal tissue development (n = 30), and those with normal protein levels for both of these protein groups (n = 7). The main subgroup of controls clustering with the MS patients showing increased inflammation and decreased neuronal tissue development were patients suffering from chronic fatigue. Our data indicate that the preferable way to quantify proteins in CSF is to first match the samples on total protein amount and then normalize the data based on the median intensities, preferably from the CNS‐enriched proteins.     

参麦注射液与布地奈德联合治疗急性酒精中毒伴吸入性肺炎的临床疗效

目的:探讨参麦注射液与布地奈德联合治疗急性酒精中毒伴吸入性肺炎的临床疗效及对肝功能和炎症指标的影响。方法:选择2014年3月至2015年8月在我院接受治疗的120例急性酒精中毒伴吸入性肺炎患者为研究对象,按照随机数字表法分为治疗组和对照组,每组60例患者,对照组给予布地奈德治疗,治疗组在对照组的基础上给予参麦注射液治疗,观察两组患者的临床疗效、症状消失时间、肝功能及血清肿瘤坏死因子-α、IL-6和IL-8炎性细胞因子的变化。结果:治疗组的总有效率为95.00%显著高于对照组的83.00%,差异有统计学意义(X~2=-4.227,P=0.039)。治疗组的哮鸣音、湿罗音、咳嗽和气喘消失时间明显短于对照组,差异有统计学意义(P0.005)。治疗组的肝功能ALT、AsT和GGT明显改善,炎性因子TNF-α、IL-6和IL-8水平下降明显,差异均有统计学意义(P0.005)。结论:参麦注射液与布地奈德联合治疗急性酒精中毒伴吸入性肺炎疗效确切,可以有效缩短患者的症状消失时间,改善肝功能,减轻炎症反应,值得临床推广应用。     

PCOS患者外周血白细胞计数变化的临床意义

目的:探讨多囊卵巢综合征(PCOS)患者外周血白细胞计数和血脂代谢变化的临床意义。方法:随机抽取2012年1月~2014年1月期间来院就诊未经药物治疗的PCOS患者48例作为研究对象,将体重指数(BMI)≥23的患者26例作为PCOS超重组,将BMI23的22例患者作为PCOS体重正常组,选择同期来院就诊的非PCOS妇女20例作为对照组,所有患者均于月经期空腹静脉抽血3~4m L,检测患者的血浆C反应蛋白(CRP)、血常规及血脂代谢指标。结果:PCOS超重组的甘油三酯(TG)、低密度脂蛋白(LDL-C)、载脂蛋白B(Apo-B)、外周白细胞总数、淋巴细胞、中性粒细胞、单核细胞、嗜酸性细胞、CRP指标均较对照组、PCOS体重正常组高,而高密度脂蛋白(HDL-C)、载脂蛋白A(Apo-A)水平较对照组、PCOS体重正常组低,差异均有统计学意义(P0.05);PCOS体重正常组淋巴细胞、CRP指标较对照组高,差异均有统计学意义(P0.05)。结论:慢性炎症是PCOS的主要病理表现,其中体重超重的PCOS患者主要表现为血脂代谢异常及白细胞升高,而体重正常的PCOS患者主要表现为淋巴细胞升高。