利尿酸是打开血-迷路屏障的钥匙

目的观察在不同的时机应用利尿酸以暂时破坏耳蜗血管纹上皮是否能够开放血-迷路屏障,从而促使庆大霉素进入耳蜗或者从耳蜗排出.方法听神经动作电位测试技术,全耳蜗毛细胞计数定量观察技术和荧光偏振免疫法测定庆大霉素浓度的技术被用于以下两个不同目的的实验观察.(1)当庆大霉素血中浓度高于内耳液浓度时,应用利尿酸破坏蜗管外壁以促使更多的庆大霉素进入耳蜗以制备不同程度耳蜗损害的动物模型.(2)当庆大霉素内耳浓度高于血中浓度时,应用利尿酸损坏蜗管外壁以促使蓄积在耳蜗内的庆大霉素从内耳排出以达到挽救毛细胞的目的.结果1.当庆大霉素血中浓度高于内耳液浓度时,注射利尿酸可造成更多的毛细胞损害和听功能障碍,外淋巴中药物的峰值浓度和半衰期浓度也均比单独一次注射庆大霉素动物外淋巴中药物浓度增加一倍,说明同时注射利尿酸可促使更多的庆大霉素从血液进入耳蜗并造成更严重的毛细胞损害.2.当血液中庆大霉素排空之后,注射利尿酸可减少毛细胞数量的损失程度,同时发现延迟注射利尿酸组动物的听力损失程度比不经利尿酸处理动物组有所减轻,外淋巴中药物浓度也比不经利尿酸处理动物组降低一半,说明当GM在耳蜗内蓄积但血清中已经排空时注射EA有助于降低药物在耳蜗内的蓄积并挽救尚未被破坏的毛细胞.结论利尿酸可以做为打开血-迷路屏障的钥匙,但是应用利尿酸开放血-迷路屏障可以产生双向结果,其关键在于注射利尿酸的时机.     

Functional localization of epileptic foci in cats using manganeseenhanced MRI

Objective： To determine the encephalic region correlated with epilepsy by manganese-enhanced MRI （MEMRI） and determine the correlation of epilepsy with calcium overloading. Methods： The cats were divided into two groups. The first group underwent EEG examination and ethological observation. The second group underwent MEMRI measurement. Signal enhanced encephalic regions were sectioned. Results： The achievement ratio of convulsive cats intramusclelarly injected with PTZ was 80%. MEMRI showed diffuse signal enhancement in the cerebral cortex of the cats with generalized tonic-clonic convulsive seizures compared with control animals. The enhancement rate of frontal-parietal-occipital lobe was 34.6% and 22.9% in temporl lobe compared with the control groups. Signal enhancement on frontal-parietal lobe persisted for 24 h after epileptic seizures were induced. The neurons of enhanced encephalic regions showed obvious degeneration and necrosis. Conclusion： Seizures can be induced in cats by intramuscular injection of PTZ （55 mg/kg）. Frontal-parietal lobe is the correlated encephalic regions of epilepsy. MEMRI plays an important role in localizing and revealing pathogenesis of epileptic seizures.     

APACHEⅡ评分与重度有机磷中毒患者肠道屏障功能的相关性分析

目的 分析急性生理与慢性健康状况系统Ⅱ(APACHEⅡ)评分与重度有机磷中毒患者肠道屏障功能的相关性.方法 回顾性选取2017年1月至2019年12月安徽理工大学附属亳州市人民医院收治的119例重度有机磷中毒患者.按照患者预后情况,将患者分别纳入存活组80例、病死组39例.记录患者入院即刻及入院48、72、144 h ...     

多药耐药蛋白1和多药耐药相关蛋白5、7在糖尿病小鼠视网膜中表达的变化

目的 观察多药耐药蛋白1(muhidrug resistance 1,MDR1)、多药耐药相关蛋白(multidrug resistance-associated protein,MRP)5和MRP7在不同时期糖尿病小鼠视网膜中的表达变化.方法 通过腹腔注射链脲佐菌素诱导C57 BL/6小鼠建立糖尿病模型,伊文思蓝灌注检测血-视网膜内屏障变化.分别于糖尿病造模成功后的4周、12周和24周取小鼠视网膜,进行实时定量-PCR、免疫荧光、Western blotting等实验,检测各组小鼠视网膜中MDR1、MRP5和MRP7的表达变化.结果 伊文思蓝灌注结果显示在糖尿病12周就出现视网膜渗漏;实时定量-PCR结果发现与对照组相比,随糖尿病进展,MDR1、MRP5和MRP7在4周、12周和24周的表达均呈下降趋势(MDR1:P4周=0.028,P12周=0.003,P24周＜0.001;MRP5:P4周=0.045,P12周=0.009,P24周＜0.001;MRPy7:P4周=0.019,P12周＜0.001,P24周 =0.001),在糖尿病不同时期其变化也呈下降趋势(均为P＜0.05);免疫荧光观察到MDR1、MRP5和MRP7的荧光强度随糖尿病发展逐渐减弱;Western blotting检测可见在4周、12周、24周糖尿病小鼠视网膜中MDR1、MRP5和MRP7的表达均呈下降趋势.结论 在DR早期血-视网膜内屏障会受到破坏,视网膜中外排转运蛋白的表达也会受糖尿病的影响导致不同程度的下降.     

Astrocytes in the damaged brain: Molecular and cellular insights into their reactive response and healing potential

Long considered merely a trophic and mechanical support to neurons, astrocytes have progressively taken the center stage as their ability to react to acute and chronic neurodegenerative situations became increasingly clear. Reactive astrogliosis starts when trigger molecules produced at the injury site drive astrocytes to leave their quiescent state and become activated. Distinctive morphological and biochemical features characterize this process (cell hypertrophy, upregulation of intermediate filaments, and increased cell proliferation). Moreover, reactive astrocytes migrate towards the injured area to constitute the glial scar, and release factors mediating the tissue inflammatory response and remodeling after lesion. A novel view of astrogliosis derives from the finding that subsets of reactive astrocytes can recapitulate stem cell/progenitor features after damage, fostering the concept of astroglia as a promising target for reparative therapies. But which biochemical/signaling pathways modulate astrogliosis with respect to both the time after injury and the type of damage? Are reactive astrocytes overall beneficial or detrimental for neuroprotection and tissue regeneration? This debate has been animating this research field for several years now, and an integrated view on the results obtained and the possible future perspectives is needed. With this Commentary article we have attempted to answer the above-mentioned questions by reviewing the current knowledge on the molecular mechanisms controlling and sustaining the reaction of astroglia to injury and its stem cell-like properties. Moreover, the cellular/molecular mechanisms supporting the detrimental or beneficial features of astrogliosis have been scrutinized to gain insights on possible pharmacological approaches to enhance astrocyte neuroprotective activities.     

Functional Fiber Reduces Mice Obesity by Regulating Intestinal Microbiota

Obesity may cause metabolic syndrome and has become a global public health problem, and dietary fibers (DF) could alleviate obesity and metabolic syndrome by regulating intestinal microbiota. We developed a functional fiber (FF) with a synthetic mixture of polysaccharides, high viscosity, water-binding capacity, swelling capacity, and fermentability. This study aimed to investigate the effect of FF on obesity and to determine its prevention of obesity by modulating the gut microbiota. Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). The results demonstrated that 12% FF could promote a reduction in body weight and epididymal adipocyte area, augment insulin sensitivity, and stimulate heat production from brown adipose tissue (BAT) (p < 0.05). Compared with the HFD, 12% FF could also significantly improve the intestinal morphological integrity, attenuate systemic inflammation, promote intestinal microbiota homeostasis, and stabilize the production of short-chain fatty acids (SCFAs) (p < 0.05). Consistent with the results of 12% FF, the LFD could significantly reduce the body weight and epididymal adipocyte area relative to the HFD (p < 0.05), but the LFD and HFD showed no significant difference (p > 0.05) in the level of inflammation and SCFAs. Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. Additionally, the treatment with antibiotics (12% FF + AB) could inhibit the effect of FF in the HFD. The Kyoto Encyclopedia of Genes and Genomes (KEGG) function prediction revealed that 12% FF could significantly inhibit the cyanogenic amino acid metabolic pathway and decrease the serum succinate concentration relative to the HFD group. The overall results indicate that 12% FF has the potential to reduce obesity through the beneficial regulation of the gut microbiota and metabolites.     

Advances in brain drug targeting and delivery: limitations and challenges of solid lipid nanoparticles

Introduction: With the advancement in the field of medical colloids and interfacial sciences, the life expectancy has been greatly improved. In addition, changes in the human lifestyle resulted in development of various organic and functional disorders. Central nervous system (CNS) disorders are most prevalent and increasing among population worldwide. The neurological disorders are multi-systemic and difficult to treat as portal entry to brain is restricted on account of its anatomical and physiological barrier.

Areas covered: The present review discusses the limitations to CNS drug delivery, and the various approaches to bypass the blood brain barrier (BBB), focusing on the potential use of solid lipid nanoparticles (SLN) for drug targeting to brain. The methods currently in use for SLN production, physicochemical characterization and critical issues related to the formulation development suitable for targeting brain are also discussed.

Expert opinion: The potential advantages of the use of SLN over polymeric nanoparticles are due to their lower cytotoxicity, higher drug loading capacity and scalability. In addition, their production is cost effective and the systems provide a drug release in a controlled manner up to several weeks. Drug targeting potential of SLN can be enhanced by attaching ligands to their surface.     

Balsalazine decreases intestinal mucosal permeability of dextran sulfate sodium-induced colitis in mice

Aim： To investigate the effect of balsalazine treatment on intestinal mucosal permeability in dextran sulfate sodium （DSS）-induced colitis and to determine the mechanism of the balsalazine-induced changes.
Methods： Experimental colitis was induced in C57BL/6J mice by the administration of 5% DSS. Balsalazine was administered intragastrically at doses of 42, 141, and 423 mg/kg. The disease activity index （DAI） score was evaluated and colon tissue was collected for the assessment of histological changes. The amount of malondialdehyde （MDA） in the colon was determined, along with the activity of myeloperoxidase （MPO）, superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px）. Mucosa from the small intestine was collected to determine the levels of tumor necrosis factor （TNF）-α and interferon （IFN）-γ. The mucosa was ultrastructurally examined with transmission electron microscopy and intestinal permeability was assayed using Evans blue.
Results： Balsalazine was found to reduce the DAI score and the histological index （HI） score, decrease the MDA content and the activity of MPO, and increase the activity of SOD and GSH-Px in colitis mice. At the same time, balsalazine ameliorated microvillus and tight junction structure, resulting in a decrease in the amount of Evans blue permeating into the intestinal wall and the levels of TNF-α and IFN-γ in colitis mice.
Conclusion： In colitis mice, the anti-colitis effect of balsalazine results in a decrease in intestinal mucosal permeability. The mechanism of this effect is partly associated with balsalazine＇s antioxidative and anti-inflammatory effects.     

三七总皂甙对实验性脑缺血脑血流及血脑屏障的影响作用

目的 观察三七总皂甙对脑缺血后再灌流期间血脑屏障及脑血流的影响。方法 利用大鼠局灶性脑缺血再灌流和全脑缺血再灌流损伤两种实验模型。结果 与相应对照组比较，不论是全脑缺血还是局灶性脑缺血1h后再灌注3d，应用三七总皂甙的各组动物及水肿明显减轻，血脑屏障通透性改善，大脑局部血流量显著增加。结论 三七总皂甙对脑缺血后脑水肿、血脑屏障、大脑局部血流量具有保护作用。