杜仲苷对炎性环境下软骨细胞的增殖和Ⅱ型胶原蛋白分泌的影响

目的：观察杜仲苷对IL-1β刺激大鼠体外软骨细胞的增殖及Ⅱ型胶原蛋白分泌的影响。方法：利用IL-1β刺激建立体外大鼠软骨细胞炎性模型,实验分为空白组、IL-1β组、10μM杜仲苷组、100μM杜仲苷组、500μM杜仲苷组、1000μM杜仲苷组;空白组加入10%FBS培养液,IL-1β组加入10ng/mL IL-1β＋10%FBS培养液,4个不同浓度杜仲苷组分别加入10μM、100μM、500μM、1000μM杜仲苷＋10ng/mL IL-1β＋10%FBS培养液,分别培养48小时,采用CCK8检测软骨细胞增殖活力及Ⅱ型胶原蛋白的分泌。结果：IL-1β组的OD值低于空白组（P〈0.05）;4个不同浓度杜仲苷组的OD值均高于IL-1β组（P〈0.05）,且存在一定的量效关系;4个不同浓度杜仲苷组的Ⅱ型胶原蛋白表达均高于IL-1β组（P〈0.05）,且存在有一定的量效关系。结论：杜仲苷可以提高体外大鼠软骨细胞炎性环境下的增殖活力,促进Ⅱ型胶原蛋白的分泌,表明杜仲苷对体外大鼠软骨细胞有一定的抗炎保护作用。     

磁共振成像(T2*)检测重型β-地中海贫血患儿心脏、肝脏铁负荷及左心室射血分数的研究

目的观察我院重型β-地中海贫血(β-TM)患儿血清铁蛋白(SF)和体内铁沉积状况及对心脏功能的影响。方法检测我院28例重型β-TM患儿SF水平,并由我院放射科运用磁共振成像T2*(MRI T2*)技术检测心脏及肝脏铁沉积状况及左室射血分数(LVEF)。结果本组28例患儿中男16例,女12例,中位年龄11.2岁(7岁1个月~16岁11个月)。28例患儿中SF轻度升高者4例(14.3%),中度升高者8例(28.6%),高度升高者16例(57.1%)。肝脏MRI T2*检测结果 :肝铁轻度沉积2例(7.1%),中度沉积8例(28.6%),重度沉积18例(54.8%);心脏MRI T2*检测结果 :心铁正常16例(57.1%),轻度铁沉积4例(14.3%),中度铁沉积4例(14.3%),重度铁沉积4例(14.3%);LVEF降低者19例(67.9%),4例心脏重度铁沉积患儿中有3例(75%)LVEF明显降低(≤55%)。本组患儿SF水平与肝脏T2*值(r=-0.467,P=0.036)、心脏T2*值(r=-0.486,P=0.01)呈明显负相关;SF与输血量呈正相关(r=0.634,P=0.043;r=0.067,P=0.124)而与去铁治疗呈负相关(r=-0.526,P=0.043),SF和心脏T2*值与LVEF均无相关性(r=-0.154,P=0.306;r=0.067,P=0.124)。结论重型β-TM患儿SF增高及肝脏重度铁沉积发生率高,虽然心脏重度铁沉积患儿发生率不高,但心脏重度铁沉积患儿多有LVEF明显降低。     

去卵巢对大鼠泪腺中IL-17A等炎症因子表达的影响

目的建立去卵巢大鼠模型,观察性激素水平改变对泪腺中IL-17A以及IL-1β、IL-6、TNF-α等炎症因子表达的影响。方法实验研究。健康雌性SD大鼠20只随机分为2组,实验组（10只）摘除大鼠双侧卵巢,对照组（10只）为未摘除卵巢的模拟手术组。术前及术后第1个月、第2个月、第3个月时2组均行泪液分泌试验（SIT）、角膜荧光染色检查进行眼表评估。于第3个月时放射免疫分析法分别检测2组大鼠血清雌二醇、睾酮含量,HE染色观察泪腺上皮细胞形态,免疫组化染色法、Western Blot法检测2组泪腺中IL-17A、IL-1β、IL-6、TNF-α的表达。2组性激素质量浓度比较、炎症因子A值表达比较均应用独立样本t检验。2组各时间点的SIT结果比较采用重复测量资料两因素方差分析。结果实验组大鼠去卵巢后第3个月时,体内雌二醇浓度低于对照组（t=-35.37,P<0.01）,睾酮浓度低于对照组（t=-12.13,P<0.01）。2组各时期SIT检查未见泪液分泌减少、均未见角膜荧光染色。HE染色见实验组泪腺腺泡萎缩,排列紊乱,胞质内酶原颗粒明显减少。泪腺IL-17A表达量2组比较实验组高于对照组（免疫组化法：t=7.56,P<0.01;Western Blot法：t=20.90,P<0.01）。余各因子表达量实验组也均高于对照组（免疫组化法：IL-1β：t=13.71,P<0.01;IL-6：t=13.92,P<0.01;TNF-α：t=6.11,P<0.01。Western Blot法：IL-1β：t=16.93,P<0.01;IL-6：t=12.46,P<0.01;TNF-α：t=14.47,P<0.01）。结论大鼠去卵巢3个月时性激素水平降低,未见明显眼表损害。但泪腺中炎症因子IL-17A、IL-1β、IL-6、TNF-α的表达增加。     

TGF-β_1在PCOS卵巢间质纤维化形成中的作用

目的:探讨TGF-β1在PCOS大鼠卵巢间质纤维化、包膜硬化形成中的作用。方法:利用脱氢表雄酮(DHEA)皮下注射的方法建立PCOS病理模型大鼠20只,用微粒子酶免分析法测定血清性激素E2、T、LH、FSH、LH/FSH、空腹胰岛素(FINS)水平,及光镜下观察PCOS大鼠卵巢的病理结构,透射电镜观察细胞超微结构来验证模型。采用免疫组化法检测PCOS组(n=20)卵巢细胞因子TGF-β1的表达,并与20只正常大鼠相比照。结果:TGF-β1在PCOS组各阶段卵泡卵母细胞、颗粒细胞的表达强度与对照组相比,差异无统计学意义(P>0.05)。而在窦状卵泡膜细胞和卵巢间质细胞中的表达,PCOS组显著高于对照组(P<0.01,P<0.05)。结论:多囊卵巢中TGF-β1表达异常,可能是导致多囊卵巢间质纤维化、包膜增厚的原因之一,TGF-β1也参与PCOS卵泡发育、闭锁的调控。     

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.     

乳腺癌组织中TRβ1基因表达及临床意义

目的:探讨甲状腺素受体β1(TRβ1)在乳腺癌组织中的表达及临床意义。方法:运用半定量逆转录聚合酶链反应(RT-PCR)技术检测40例乳腺癌及10例正常乳腺组织中TRβ1基因表达情况。结果:TRβ1基因在10例正常乳腺组织中全部表达,而TRβ1基因在40例乳腺癌组织中mRNA表达下降34例(85%)。乳腺癌组织中TRβ1基因表达明显低于正常乳腺组织(P<0.05)。不同年龄的患者TRβ1基因mRNA的表达差异无统计学意义(P>0.05),在不同临床分期、淋巴有无结转移、ER的阳性与阴性表达及肿瘤大小不同的患者中,TRβ1基因mRNA的表达差异有统计学意义(P<0.05)。结论:TRβ1在乳腺癌的浸润和转移方面起重要作用,可成为评估乳腺癌严重程度的新指标。     

敲低着丝粒蛋白U对顺铂耐药卵巢癌细胞自我更新、顺铂耐药和Wnt/β-catenin信号活性的抑制作用

目的:探讨下调着丝粒蛋白U(CENPU)对卵巢癌(OC)细胞顺铂耐药的影响,并分析其作用机制.方法:采用Western blotting法检测OC细胞(OVCAR3和SKOV3细胞)和顺铂耐药OC细胞(OVCAR3/DDP和SKOV3/DDP细胞)中CENPU蛋白表达水平.将OVCAR3/DDP和SKOV3/DDP细胞...     

探究哮喘患者血清IL-13、VEGF、TGF-β1与气道炎症反应的相关性

目的 探究与分析哮喘患者血清白介素-13 (IL-13)、血管内皮生长因子(VEGF)、转化生长因子-β1 (TGF-β 1)与气道炎症反应的相关性.方法 选取本院自2013年8月至2015年8月收治的80例哮喘患者,按照急性发作期与临床缓解期分为观察A组与观察B组,每组各40例,另选择同时收治的健康体检人员40例作为对照组,测量三组人员的血清IL-13、VEGF、TGF-β 1,并给予肺功能检查,对结果行统计学分析.结果 观察B组与观察A组相比IL-13、VEGF、TGF-β 1均较低,FEV1及FEV1/FVC均较高,差异具有统计学意义(P＜0.05).对照组与观察B组相比IL-13、VEGF、TGF-β 1均较低,FEV1及FEV1/FVC均较高,差异具有统计学意义(P＜0.05).血清IL-13、VEGF、TGF-β 1水平互相呈正相关性,即三者若其中一项升高,另外两项也随之升高(P＜0.05).血清IL-13、VEGF、TGF-β 1水平与FEV1及FEV 1/FVC分别均呈负相关性,即血清IL-13、VEGF、TGF-β 1水平升高时,FEV1及FEV 1/FVC降低(P＜0.05).结论 哮喘患者血清IL-13、VEGF、TGF-β 1与气道炎症反应具有一定的相关性,为临床治疗与诊断提供重要基础.     

羧甲基-β-环糊精为手性选择剂拆分托吡卡胺等4种手性药物对映体

目的以羧甲基-β-环糊精(CM-β-CD)为手性选择剂,建立毛细管区带电泳法分离托吡卡胺、文拉法辛、美托洛尔和瑞格列奈4种药物对映体。方法采用未涂壁熔融石英毛细管柱,磷酸盐缓冲液作为背景电解质溶液,分离电压为20 kV。考察了缓冲溶液的pH值、环糊精质量浓度、缓冲盐浓度对对映体分离的影响。结果在优化的分离条件下,4种手性药物均能达到完全分离。结论CM-β-CD适用于上述4种药物的对映体分离。     

Acute systemic exposure to silver-based nanoparticles induces hepatotoxicity and NLRP3-dependent inflammation

Nanoparticles (NPs) are increasingly being commercialized for use in biomedicine. NP toxicity following acute or chronic exposure has been described, but mechanistic insight into this process remains incomplete. Recent evidence from in vitro studies suggested a role for NLRP3 in NP cytotoxicity. In this study, we investigated the effect of systemic administration of composite inorganic NP, consisting of Ag:Cu:B (dose range 1–20?mg/kg), on the early acute (4–24?h post-exposure) and late phase response (96?h post-exposure) in normal and NLRP3-deficient mice. Our findings indicate that systemic exposure (≥2?mg/kg) was associated with acute liver injury due to preferential accumulation of NP in this organ and resulted in elevated AST, ALT and LDH levels. Moreover, within 24?h of NP administration, there was a dose-dependent increase in intraperitoneal neutrophil recruitment and upregulation in gene expression of several proinflammatory mediators, including TNF-α, IL-1β and S100A9. Histological analysis of liver tissue revealed evidence of dose-dependent hepatocyte necrosis, increase in sinusoidal Kupffer cells, lobular granulomas and foci of abscess formation which were most pronounced at 24?h following NP administration. NP deposition in the liver led to a significant upregulation in gene expression of S100A9, an endogenous danger signal recognition molecule of phagocytes, IL-1β and IL-6. The extent of proinflammatory cytokine activation and hepatotoxicity was significantly attenuated in mice deficient in the NLRP3 inflammasome, demonstrating the critical role of this innate immune system recognition receptor in the response to NP.