褪黑素对PM 2.5暴露大鼠肺部炎症反应和氧化应激的影响

为探讨褪黑素对大气细颗粒物(PM 2.5)暴露大鼠肺部炎症反应和氧化应激的影响及其机制,本实验将48只清洁级SD大鼠随机(随机数字法)分成4组:空白对照组、NS对照组、PM 2.5组及褪黑素(MT)组,通过气管向肺内注入PM 2.5悬液构建大鼠肺组织PM 2.5染毒模型,并通过灌胃MT溶液,采用肺组织HE染色、ELISA法及蛋白印迹等方法分别检测肺组织病理改变、TNF-α、IL-6、IL-1、MPO、SOD及MDA表达以及NF-κBp65蛋白表达。结果显示:(1)与空白对照组及NS对照组比较,PM 2.5组大鼠肺组织出现明显损伤改变,MT组大鼠肺组织损伤较PM 2.5组明显减轻;(2)PM 2.5组大鼠肺组织TNF-α、IL-6、IL-1表达出现明显增加(p0.05),MT组较PM 2.5组TNF-α、IL-6、IL-1表达明显下降(p0.05);(3)PM 2.5组大鼠肺组织SOD表达较空白对照组及NS对照组明显下降(p0.05),而MPO及MDA表达明显增加(p0.05),而与PM 2.5组比较,MT组大鼠肺组织SOD表达出现增加,MPO及MDA表达下降(p0.05);(4)PM 2.5组P65蛋白表达出现明显上调(p0.05),而MT组较PM 2.5组P65蛋白表达出现明显下降(p0.05)。由此得出结论,PM 2.5能通过介导肺组织炎性反应及氧化应激导致肺组织损伤,且与活化NF-κB相关,褪黑素能显著抑制PM 2.5所致NF-κB活化,减轻炎性反应及氧化应激,改善PM 2.5暴露大鼠肺损伤。     

AQP1在阿霉素肾病大鼠器官水肿中作用研究

目的：探究阿霉素肾病是否引起除肾脏外的器官水肿,以及水通道蛋白1(Aquaporin 1,AQP1)的表达变化在器官水肿形成中的作用。方法：将20只SD大鼠随机分为模型组和对照组。模型组予尾静脉注射盐酸阿霉素（6.0 mg/kg）造模,对照组注射等量生理盐水。造模6周后处死,记录体重和心、肝、脾、肺重量,应用HE染色法对心、肝、脾、肺组织进行病理学观察,使用IHC法检测AQP1在心、肝、脾、肺组织的分布,使用Western blot法和RT-PCR法检测各器官组织中AQP1的蛋白和m RNA表达水平。结果：与对照组相比,阿霉素肾病大鼠尿蛋白显著升高（P<0.01）,体重显著降低（P<0.05）,肺系数显著升高（P<0.05）,但心、肝、脾重量没有显著变化。心、肝、肺均出现不同程度的水肿和病理损伤,脾表现出血液充盈不足;免疫组化结果显示AQP1分布于肝脏胆管细胞、心脏肌细胞膜及微血管内皮细胞、脾血红细胞、肺毛细血管内皮细胞。Western blot和RT-PCR结果显示模型组心脏AQP1蛋白和m RNA表达水平均显著增高（P<0.05）,肝脏AQP1蛋白表达水平有...     

盐酸氨溴索对烟所致慢性阻塞性肺疾病大鼠肺组织细胞凋亡和血管重塑的作用机制研究

目的:盐酸氨溴索对烟所致慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)大鼠肺组织细胞凋亡和血管重塑的作用机制研究。方法:将SD大鼠随机分为4组,每组20只,依次为正常组、模型组、实验组、对照组。模型组、实验组、对照组大鼠采延安香烟烟熏64天构建慢性阻塞性肺大鼠模型,正常组大鼠室温下正常饲养。烟熏结束后,实验组、对照组大鼠每日分别皮下注射5ml盐酸氨溴索(20 mg/kg)和5 m L的盐酸班布特罗(20 mg/kg),正常组、模型组分别腹腔注射等剂量的生理盐水。在药物干预28天后,苏木精-伊红染色(hematoxylin-eosinstaining,HE)、弹力纤维(elastic van gieson,EVG)染色、TUNNEL染色、免疫组化染色、Western blot检测各组大鼠肺组织病理、血管重塑、肺组织的细胞凋亡、α-平滑肌肌动蛋白(α-smoothmus-cleactin,α-SMA)和血管内皮生长因子(Vascular endothelial growth factor,VEGF)的表达、以及Caspase-3、Bax和Bcl-2的表达水平。结果:与正常组相比,模型组肺组织损伤明显,肺小动脉中膜厚度明显增加,血管肌化程度、细胞的凋亡率、α-SMA和VEGF、Caspase-3、Bax的表达明显升高,Bcl-2的表达明显降低,差异均具有统计学意义(P0.05);与模型组相比,实验组和对照组大鼠肺组织损伤明显改善,肺小动脉中膜厚度明显减小,血管肌化程度、细胞的凋亡率、α-SMA和VEGF、Caspase-3、Bax的表达明显降低,Bcl-2的表达明显升高,差异均具有统计学意义(P0.05)。结论:盐酸氨溴索能抑制肺组织的细胞凋亡以及改善其血管重塑,保护COPD大鼠的肺组织。     

MMP-9、ICAM-1、TNF-α在自发性高血压大鼠烟熏肺损伤中的变化分析

探讨MMP-9、ICAM-1和TNF-α在自发性高血压大鼠烟熏肺损伤中的表达变化及其作用机制。选取健康、雄性Wister大鼠12只(对照组),自发性高血压雄性Wister大鼠24只随机分为烟熏组和SH对照组各12只,对照组和烟熏组均每天进行烟熏2次、每周6 d,连续8周对比3组大鼠肺功能变化、肺组织中细胞粘附分子-1(ICAM-1)、肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶-9(MMP-9)蛋白及mRNA的表达情况。对照组、烟熏组的气道阻力、平滑肌指数、胶原指数均显著的高于SH对照组(p0.05),对照组、烟熏组的最大呼气流量、平均肺泡个数均低于SH对照组(p0.05);烟熏组的气道阻力、平滑肌指数、胶原指数均显著的高于对照组(p0.05),烟熏组的最大呼气流量、平均肺泡个数均低于对照组(p0.05);对照组、烟熏组的ICAM-1、TNF-α、MMP-9蛋白、mRNA表达程度均显著的高于SH对照组(p0.05);烟熏组的ICAM-1、TNF-α、MMP-9蛋白、mRNA表达程度均显著的高于对照组(p0.05)。烟熏对自发性高血压大鼠肺功能的损伤十分明显,破坏肺泡结构,影响大鼠的肺部功能,该过程可能与上调ICAM-1、TNF-α、MMP-9表达有关。     

COPD大鼠肺组织中小窝蛋白-1 的表达及其与气道重塑的关系

目的:探讨小窝蛋白-1(Caveolin-1)在COPD大鼠肺组织中的表达及其与气道重塑的关系。方法:采用10周龄Wister大鼠20只,随机分为对照组与实验组,每组10只,对照组常规饲养,实验组采用烟熏法+内毒素法建立COPD模型。第91天处死全部大鼠,测定肺功能后取肺组织,采用免疫组织化学法检测Caveolin-1的表达;酶联免疫吸附试验(ELISA)检测各组大鼠肺组织匀浆中白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)、转化生长因子-β1(TGF-β1)的含量;分析Caveolin-1的表达与IL-8、TNF-α、TGF-β表达的相关性。结果:与对照组比较,实验组大鼠的肺顺应性明显下降,肺弹性阻力及气道阻力显著升高,肺组织TNF-α、IL-8、TGF-β1的含量明显升高,Caveolin-1的表达明显降低,差异均有统计学意义(P0.05)。大鼠肺组织中Caveolin-1的表达与IL-8、TNF-α、TGF-β1含量呈显著负相关(P0.05)。结论:Caveolin-1在COPD大鼠肺组织中的表达明显降低,可能通过促进炎性细胞因子的释放与气道重塑参与COPD的发生和发展。     

妊娠期PM2.5,暴露影响子代鼠主要脏器发育

目的探讨妊娠期大气细颗粒物PM2.5(颗粒直径≤2.5μm)暴露对子代鼠主要脏器发育的影响。方法孕鼠随机分为空白组、对照组、PM2.5低剂量组、PM2.5中剂量组、PM2.5高剂量组。利用气管滴注方法,建立小鼠妊娠期PM2.5暴露模型。通过HE染色和PAS反应,观察妊娠期暴露于PM2.5后新生子代鼠主要脏器的病理形态学改变,通过电子显微镜观察细胞超微结构变化。结果与空白组和对照组相比,PM2.5模型组新生子代鼠心、肝、脾、肺和肾组织结构均受损,可见炎症等病理改变。子代鼠主要脏器超微结构出现不同程度的细胞核周隙局部增宽、自噬体增多、线粒体嵴模糊和断裂等变化。结论妊娠期暴露于PM2.5可导致新生子代鼠心、肝、脾、肺、肾等主要脏器出现组织形态异常。这可能是PM2.5致生后远期慢性疾病发生的解剖学基础和发育源性病因。     

HIF-1α、VEGF在慢支及COPD大鼠肺组织的表达及意义

目的:研究HIF-1α、VEGF在COPD及慢支大鼠肺组织的表达情况及意义。方法:采用烟熏法制作慢支及COPD模型,应用免疫组化法检测肺组织中HIF-1α、VEGF的表达。结果:慢支组及COPD组HIF-1α、VEGF在大鼠肺组织中的表达均较正常组增加(P<0.05);HIF-1α、VEGF在COPD组与慢支组大鼠肺组织中的表达差异无显著性(P>0.05);直线相关分析显示,模型组HIF-1α与VEGF的表达呈正相关。结论:慢支组及COPD组大鼠肺组织中HIF-1α、VEGF的表达增加,二者参与气道炎症及结构的重塑。     

木犀草素通过抑制PTEN PI3K-AKT信号通路以及对免疫功能的调节作用介导对肺癌模型大鼠的干预研究

探讨木犀草素对肺癌模型大鼠的干预作用及其对PTEN-PI3K-AKT信号通路的抑制作用和对免疫功能的影响。采用灌注致癌碘油液制备大鼠肺癌模型,分别给予木犀草素高、中、低剂量和环磷酰胺治疗16周后进行大鼠的一般情况、肺组织病理形态学和肺脏指数、脾脏指数变化的评价。酶联免疫吸附法检测各组大鼠EGF、TGF-β、VEGF的表达。流式细胞术检测各组大鼠T淋巴细胞群(CD3~+、CD4~+、CD8~+、CD4~+/CD8~+)水平。实时荧光定量PCR法检测各组大鼠AKT-1、CyclinD1、NF-κB mRNA的表达。Western blot法检测各组大鼠PTEN、p-PI3K、p-AKT蛋白的表达。结果表明木犀草素可显著改善肺癌大鼠肺组织病理情况,提高脾指数,降低肺指数,提高血CD3~+、CD4~+、CD4~+/CD8~+水平,降低CD8~+水平,显著降低肺组织中EGF、TGF-β、VEGF的表达及AKT-1、CyclinD1、NF-κB mRNA的表达水平,提高肺组织中PTEN蛋白的表达,降低P-PI3K、p-AKT蛋白表达水平。木犀草素可显著抑制肺癌的增殖和转移,其机制可能与促进免疫器官的发育和分化,促进T淋巴细胞亚群的功能,提高机体免疫功能和下调PI3K/AKT信号通路的活性来发挥作用的。     

VEGF与其受体2在哮喘大鼠气道中表达变化及其对气道平滑肌细胞增殖的影响

目的探讨血管内皮生长因子(VEGF)及其受体2(Flk-1)在哮喘大鼠气道中表达变化及其对气道平滑肌细胞增殖的影响.方法 SD大鼠18只,随机分为对照组,哮喘模型组和地塞米松干预组各6只.以腹腔注射1%卵蛋白致敏和2%卵蛋白雾化吸入激发复制哮喘模型,干预组在每次激发前给予地塞米松干预.用免疫组织化学技术检测气道平滑肌α-actin以及VEGF和Flk-1蛋白质在不同组大鼠肺组织的表达程度;用RT-PCR方法检测VEGF和Flk-1mRNA在不同组大鼠肺组织的表达程度;采用HMIAS-2000型高清晰度彩色医学图文分析系统进行图像分析.结果 (1)哮喘模型组气道壁平滑肌厚度较对照组和干预组显著增加(P<0.05).(2)哮喘模型组VEGF及Flk-1蛋白质在大鼠肺组织中的表达较对照组和干预组显著增加(P<0.05).(3)哮喘模型组VEGF144,VEGF188 mRNA和VEGF205 mRNA在大鼠肺组织中的表达较对照组和干预组显著增加(P<0.05或P<0.01).哮喘模型组Flk-1mRNA在大鼠肺组织中的表达较对照组和干预组显著增加(P<0.05).直线相关性分析显示,气道壁平滑肌厚度与大鼠肺组织中VEGF205,188,144及Flk-1mRNA表达水平呈正相关(r分别为0.739,0.747,0.744,0.682;P<0.05);气道壁平滑肌厚度与大鼠肺组织中VEGF及Flk-1蛋白质表达水平也呈正相关(r分别为0.693,0.672;P<0.05).结论哮喘模型大鼠肺组织中VEGF及其受体Flk-1表达上调,并与气道平滑肌增殖有密切关系.该结果提示VEGF及其受体2可能参与了哮喘气道重建中气道平滑肌增殖的过程.     

经肺炎衣原体感染的SD大鼠的病理学特征变化分析研究

摘要 目的：探讨与分析大鼠肺炎衣原体感染后的病理学特征变化。方法：研究时间为2019年5月到2020年2月。将30只斯泼累格?多雷(Sprague Dawley,SD)大鼠随机分为2组-实验组与对照组,每组各15只大鼠。实验组大鼠从鼻腔吸入40 μL 含1×103感染颗粒的肺炎衣原体,对照组吸入等剂量的无菌磷酸液缓冲液。观察与检测大鼠一般行为、血液学指标与病理学变化情况。结果：实验组肺实变面积达25 %~50 %,细支气管和小血管周围出现小灶性淋巴细胞及单个核细胞聚集,肺泡腔有大量炎性渗出,肺泡壁伴随有充血,支气管周围见大量嗜中性粒细胞浸润。小鼠一般行为表现为活力下降,毛发皱乱,进食和饮水减少,进食明显减少。接种后3 d,实验组的白细胞总数、中性粒细胞比例高于对照组,淋巴细胞比例低于对照组(P<0.05);实验组的血清白细胞介素-6(Interleukin-6,IL-6)、肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)浓度都显著高于对照组(P<0.05);实验组的肺炎衣原体IgG抗体相对表达水平显著高于对照组(P<0.05);实验组的血清血管内皮生长因子(Vascular endothelial growth factor,VEGF)、D-二聚体(D-dimer,D-D)表达水平都显著高于对照组(P<0.05)。结论：大鼠肺炎衣原体感染后伴随有肺组织病理损伤,也可诱发VEFG与D-D的表达,促进肺组织炎症细胞浸润,可导致大鼠白细胞总数、中性粒细胞比例增加,促进炎症因子的释放。     

河北省石家庄市第一医院

目的:检测日间和夜间Lewis肺癌小鼠血清中内血管内皮生长因子(VEGF)水平和肺癌组织中VEGF蛋白表达的差别,探讨肿瘤血管生成的昼夜节律。方法:选择C57BL小鼠30只,制备Lewis肺癌小鼠模型后随机分为日间组(D组)和夜间组(N组),在光照-黑暗条件下饲养建立统一同步化日夜节律。随着成瘤过程,应用ElISA方法测定两组小鼠模型第0、3、5、7天血清中VEGF浓度水平;成瘤后第9天处死小鼠,应用Westeon-blot法检测瘤体中VEGF蛋白的表达,并分别进行相关分析。结果:随着成瘤过程,D组小鼠血清中VEGF浓度均显著高于N组(P<0.05);D组小鼠瘤体组织中VEGF蛋白表达灰度值(8.87±1.20)均明显高于N组(6.43±1.35),有统计学意义(P<0.05)。结论:Lewis小鼠休息期(白天)血清中VEGF浓度及瘤体中VEGF蛋白表达水平均明显高于活动期(夜间),存在着明显的日夜差异,说明肺癌组织的血管生成可能具有一定日夜节律。     

血清胆红素、NO、ET-1、VEGF水平联合检测对冠心病诊断价值

摘要 目的：探讨血清胆红素、一氧化氮（NO）、内皮素-1（ET-1）、血管内皮生长因子（VEGF）水平联合检测对冠心病（CHD）的诊断价值。方法：选取2019年12月至2020年12月在我院治疗的冠心病患者65例作为观察组;另选取同期参与健康体检的60例健康人群作为对照组。对所有患者总胆红素水平（TBIL）、直接胆红素水平（DBIL）、NO、ET-1、VEGF表达水平进行检测,计算间接胆红素水平（IBIL）,采用受试者工作特征曲线（ROC）下面积（AUC）比较血清胆红素、VEGF、ET-1和NO单独和联合检测对冠心病的诊断价值,采用单因素和多因素logistic回归分析法分析冠心病的影响因素。结果：与对照组相比,观察组患者血清IBIL、DBIL、TBIL、VEGF和NO检测结果均显著降低,ET-1检测结果显著升高（P＜0.05）。血清胆红素、VEGF、ET-1和NO对冠心病联合检测的AUC值显著高于单独检测值（P＜0.05）。观察组患者高血压、糖尿病、血脂异常、吸烟、肥胖的发生率明显高于对照组（P＜0.05）。多因素非条件logistic回归分析结果显示,高血压、糖尿病、血脂异常、吸烟、肥胖、血清胆红素、VEGF、ET-1和NO均可作为评估冠心病的危险因素,其中血清检测指标的关联强度依次为ET-1、VEGF、NO、胆红素（P＜0.05）。结论：冠心病患者血清胆红素代谢异常,血管内皮功能指标紊乱,是导致患者动脉粥样硬化的重要原因。血清胆红素、NO、ET-1、VEGF水平联合检测对冠心病诊断效能明显优于单个指标,且可作为冠心病发病风险的有效指标。     

杭州市中心城区大气PM2.5暴露致大鼠肺部损伤作用研究

目的：探讨杭州市中心城区大气细颗粒物（PM2.5）对大鼠肺部的损伤及其对内质网应激通路的激活作用。方法：在杭州中心城区采用大容积空气颗粒物采样器将PM2.5颗粒采集于石英纤维滤膜上,将收集的PM2.5洗脱于超纯水中,再经真空冰冻干燥处理。将24只雄性SD大鼠随机分为3组：空白对照组,PM2.5低剂量组（5 mg/kg BW）和高剂量组（25 mg/kg BW）。采用气管滴注法进行染毒,每周1次,连续染毒4周。末次染毒24 h后麻醉动物,取左肺行HE染色,观察肺组织病理学改变。以化学比色法检测右肺肺泡灌洗液（BALF）中总抗氧化能力（T-AOC）含量、超氧化物歧化酶（SOD）活性和乳酸脱氢酶（LDH）活性,ELISA法测定BALF中肿瘤坏死因子-α（TNF-α）、白介素-1β（IL-1β）和白介素-6（interleukin-6,IL-6）水平。Western blot法检测肺组织中内质网应激标志物葡萄糖调节蛋白78（GRP78）表达、磷酸化蛋白激酶受体样内质网激酶（PERK）,磷酸化真核细胞翻译起始因子2α（eIF2α）,C/EBP同源蛋白（CHOP）,肌醇依赖酶1α（IRE1α）,X盒结合蛋白1（XBP1）蛋白的水平。结果：与空白对照组相比,低剂量和高剂量PM2.5染毒均能导致大鼠肺部出现明显的肺泡壁增厚、肺泡腔缩小、间质增生和炎细胞浸润,且随着染毒剂量增加组织损伤加重。PM2.5染毒组大鼠BALF中T-AOC含量和SOD活性呈剂量依赖性下降（P<0.05）;而BALF中的LDH活性则呈剂量依赖性上升（P<0.05）。PM2.5染毒导致大鼠肺部促炎因子TNF-α、IL-1β和IL-6的释放呈剂量依赖性增加（P<0.05）。高剂量PM2.5染毒组大鼠肺组织中GRP78、磷酸化PERK（p-PERK）、磷酸化eIF2α（p-eIF2α）、CHOP、IRE1α和剪切型X盒结合蛋白1（XBP1-S）表达显著升高,而未剪切型XBP1（XBP1-U）表达明显下降。结论：杭州市中心城区PM2.5染毒可引起大鼠肺部的炎性损伤,上述损伤可能与肺部氧化应激和内质网应激通路的激活相关。     

被动吸烟下调大鼠卵巢雌、孕激素及其受体的表达

目的利用Wistar大鼠烟雾吸入模型,观察被动吸烟对Wistar大鼠卵巢结构的影响,检测生殖激素水平,分析生殖内分泌的变化,为提倡生育期妇女避免被动吸烟提供新的理论依据。方法建立大鼠烟雾吸入模型。32只健康雌性Wistar大鼠,鼠龄(60±5)d,每只体重200～250g,随机分为空白对照组和实验组,每组16只。实验组吸烟3个月,对照组正常饲养。3个月后处死两组大鼠。酶联免疫吸附试验方法 (enzyme linkedimmunosorbent assay,ELISA)检测雌鼠血清中雌激素(estrogen,E2)、孕激素(progesterone,P4)的水平;常规石蜡切片,免疫组织化学SP法检测各组雌鼠卵巢雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)的表达情况。所得数据采用SPSS软件作统计学处理分析,比较各组间差异程度。结果①酶联免疫吸附试验结果 :吸烟3个月大鼠血清E2水平比空白对照组显著降低,其浓度值比较差异有显著性;吸烟3个月大鼠血清P4水平比空白对照组显著降低,其浓度值比较差异有显著性。②免疫组织化学结果 :ER主要表达在大鼠卵巢组织的各级生长卵泡的颗粒细胞的细胞核内,呈棕黄色颗粒状分布,卵泡膜细胞和间质细胞也有少量表达。吸烟3个月的大鼠卵巢组织中ER的表达显著低于空白对照组。PR主要表达在大鼠卵巢组织卵泡的颗粒细胞的细胞质和细胞核中,呈棕黄色颗粒状分布,吸烟3个月的大鼠卵巢组织中PR的表达显著低于空白对照组。结论①成功的建立了大鼠被动吸烟模型。②被动吸烟可使大鼠血清中E2及P4水平明显降低,使大鼠卵巢中ER及PR的表达减少,提示被动吸烟可破坏卵巢的功能,引起生殖内分泌失调。     

早期戒烟大鼠肺病理及炎性介质变化

目的观察早期戒烟后大鼠肺组织病理及炎性介质表达变化规律。方法选用Wistar雄性大鼠80只,随机分为对照组及早期戒烟后0天、1周、2周、4周、6周、8周、12周组。采用酶联免疫吸附方法测定各组大鼠血清中IL-8的蛋白质含量,S-P免疫组化学方法检测肺组织NF-κB p65的表达,并光镜下观察HE染色切片、对大鼠气道炎症进行病理学评分。结果早期戒烟组大鼠可见气道上皮细胞纤毛发生粘连、倒伏,上皮细胞空泡变形、坏死、增生,炎症细胞浸润;其血清IL-8浓度、肺组织NF-κB的表达及气道炎症病理评分在戒烟后各时相点较未吸烟对照组明显升高,有统计学意义（P〈0.05）。早期戒烟组大鼠血清IL-8的浓度、肺组织NF-κB的表达及肺组织病理炎症评分在戒烟后略有上升、且在戒烟后8周达到高峰,但随后在戒烟12周时可见IL-8的浓度有下降趋势,肺组织病理炎症反应有所减轻。结论早期戒烟大鼠在戒烟早期虽可见炎症反应略有加重,但随戒烟时间延长,仍可见炎症反应有所减轻。因此,提倡及早且坚持戒烟。     

Relation between expression of TNF alpha, iNOS, VEGF mRNA and development of heart failure after experimental myocardial infarction in rats.

An injury to the heart due to myocardial infarction (MI) may progress to heart failure. Among factors, whose interactions promote remodeling of ischemic myocardium, the increased expression of tumor necrosis factor alpha (TNFalpha), inducible nitric oxide synthase (iNOS) and Vascular Endothelial Growth Factor (VEGF) was found. However, little is known about the temporal and spatial relation between expression of iNOS, cytokine TNFalpha, and growth factor VEGF during pathological process of development of heart failure after the myocardial infarction. Male Sprague-Dawley rats were used for experimental myocardial infarction. The procedure was performed by anterolateral thoracotomy and snearing LAD with the metal clip. The hemodynamic measurements were done with the Langendorff preparation converted into a working heart system. The hemodynamic parameters were recorded at day 6, 11, 28, 40 and the myocardium for gene expression was collected at day 1, 4, 11, 28, 40. Control group was sham operated rats. The VEGF, TNFalpha, iNOS, and GAPDH genes were detected by RT-PCR assay from samples taken at border zone of myocardial infarction. Expression of isoform VEGF120 was found at day 1 and 4 after MI, whereas isoforms VEGF164 and VEGF188 along with expression of TNFalpha and iNOS was found at day 1, 4, 11, 28, 40. No expression of examined genes was detected in the myocardium of control rats. The expression of studied factors was parallel with development of heart failure after myocardial infarction assessed by hemodynamic measurements. These findings confirm the postulated involvement of TNFalpha, iNOS and growth factor VEGF in the remodeling of the myocardium and development of heart failure after experimental myocardial infarction.     

VEGF, Bcl-2 and Bad regulated by angiopoietin-1 in oleic acid induced acute lung injury

Molecular mechanisms of acute lung injury (ALI) are poorly defined. Our previous study demonstrated that recombinant angiopoietin-1 (Ang1) can protect against oleic acid (OA) induced ALI at an early stage. The purpose of this study was to elucidate whether vascular endothelial growth factor (VEGF), Bcl-2, and Bad, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) play any role in the protective mechanism of recombinant Ang1 in OA-induced ALI. All BALB/C mice were administered a single dose of OA to induce lung injury. Lungs, bronchoalveolar lavage fluid (BALF), and serum were harvested at certain time points. The expression of VEGF, Bcl-2, Bad, PI3K/Akt, and the histological changes in the lung, and the levels of VEGF, IL-6, and IL-10 in serum and BALF were examined. A second cohort of mice was followed for survival for 7 days. We observed increased expression of VEGF in BALF and serum and reduced expression of VEGF in lung tissue. Recombinant Ang1 treatment, however, up-regulated VEGF expression and p-Akt/Akt in lung tissue but down-regulated VEGF expression in BALF and serum. OA led to a decrease of anti-apoptotic marker Bcl-2 and a marked increase of pro-apoptotic marker Bad. Compared with the ALI group, in the recombinant Ang1 treated group, Bcl-2 expression was restored, and Bad expression was clearly attenuated. In addition, recombinant Ang1 attenuated the lung pathological changes and improved the survival of mice. These findings suggest that recombinant Ang1 may be a promising potential treatment for ALI. It seems that VEGF is mediated by PI3K/Akt pathway which is required for Ang1-mediated protection of lung injury. Activation of Akt stimulates expression of Bcl-2 and inhibits the expression of Bad, thus inhibiting the execution of apoptosis.     

Exposure to secondhand smoke in terraces and other outdoor areas of hospitality venues in eight European countries

Background

Outdoor secondhand smoke (SHS) concentrations are usually lower than indoor concentrations, yet some studies have shown that outdoor SHS levels could be comparable to indoor levels under specific conditions. The main objectives of this study were to assess levels of SHS exposure in terraces and other outdoor areas of hospitality venues and to evaluate their potential displacement to adjacent indoor areas.

Methods

Nicotine and respirable particles (PM2.5) were measured in outdoor and indoor areas of hospitality venues of 8 European countries. Hospitality venues of the study included night bars, restaurants and bars. The fieldwork was carried out between March 2009 and March 2011.

Results

We gathered 170 nicotine and 142 PM2.5 measurements during the study. The median indoor SHS concentration was significantly higher in venues where smoking was allowed (nicotine 3.69 µg/m3, PM2.5: 120.51 µg/m3) than in those where smoking was banned (nicotine: 0.48 µg/m3, PM2.5: 36.90 µg/m3). The median outdoor nicotine concentration was higher in places where indoor smoking was banned (1.56 µg/m3) than in venues where smoking was allowed (0.31 µg/m3). Among the different types of outdoor areas, the highest median outdoor SHS levels (nicotine: 4.23 µg/m3, PM2.5: 43.64 µg/m3) were found in the semi-closed outdoor areas of venues where indoor smoking was banned.

Conclusions

Banning indoor smoking seems to displace SHS exposure to adjacent outdoor areas. Furthermore, indoor settings where smoking is banned but which have a semi-closed outdoor area have higher levels of SHS than those with open outdoor areas, possibly indicating that SHS also drifts from outdoors to indoors. Current legislation restricting indoor SHS levels seems to be insufficient to protect hospitality workers – and patrons – from SHS exposure. Tobacco-free legislation should take these results into account and consider restrictions in the terraces of some hospitality venues to ensure effective protection.     

VEGF和IGF-I在子宫内膜异位症患者血清中的表达及临床意义

目的：探究血管内皮生长因子（VEGF）和胰岛素样生长因子-I（IGF-I）在子宫内膜异位症患者血清中的表达及临床意义,为 子宫内膜异位症的治疗提供参考。方法：选取我院2015 年1 月至2016 年1 月收治的子宫内膜异位症患者50 例为实验组,另选 体检中心健康妇女50 例为对照组。实验组患者根据疾病不同分期分为I、II期（n=24）和III、IV 期（n=26）。通过酶联免疫吸附法 （ELISA）检测两组对象血清中VEGF和IGF-I的水平,采用Pearson相关分析法分析实验组患者血清中VEGF 和IGF-I 表达的相 关性。结果：实验组患者血清中VEGF和IGF-I的水平均明显高于对照组,差异有统计学意义（P<0.05）;实验组III、IV期患者血清 中VEGF和IGF-I的水平明显高于I、II期患者,差异有统计学意义（P<0.05）;Pearson 相关性分析显示实验组患者血清中VEGF 和IGF-I的水平变化呈正相关关系（r=0.507,P<0.05）。结论：子宫内膜异位症患者血清中VEGF和IGF-I的水平高于正常水平,并 随着病情的加重而不断升高,且二者呈正相关关系,可协同作用加快病情发展。     

Impaired VEGF and nitric oxide signaling after nitrofen exposure in rat fetal lung explants

We hypothesized that abnormal fetal lung growth in experimental congenital diaphragmatic hernia after maternal nitrofen exposure alters lung structure due to impaired VEGF signaling, which can be reversed with VEGF or nitric oxide (NO) treatment. Timed-pregnant Sprague-Dawley rats were treated with nitrofen on embryonic day 9 (E9), and fetal lungs were harvested for explant culture on E15. Explants were maintained in 3% O2 for 3 days and were treated with NO gas or recombinant human VEGF protein for 3 days. To determine the effects of VEGF inhibition on lung structure, normal fetal lung explants were treated with SU-5416, a VEGF receptor inhibitor, with or without exogenous NO or VEGF. We found that nitrofen treatment impaired lung structure, as evidenced by decreased branching at day 0, but lung structure was not different from controls after 3 days in culture. Nitrofen reduced lung VEGF but not endothelial NO synthase protein level. Treatment with NO enhanced lung growth in control and nitrofen-exposed lungs; however, the response to NO in the nitrofen-treated lungs was reduced when compared with controls. VEGF treatment did not cause a further increase in lung complexity after nitrofen exposure. SU-5416 treatment altered lung structure, which improved with NO but not VEGF treatment. Both nitrofen and SU-5416 treatment increased apoptosis in the mesenchyme of fetal lung explants. We conclude that nitrofen exposure increased apoptosis, decreased lung growth and reduced VEGF expression, and that exogenous NO but not VEGF treatment enhances lung growth. Disruption of lung architecture after VEGF receptor blockade was similar to nitrofen-induced changes but was more responsive to NO.