泛素羧基末端水解酶L1、胶质纤维酸性蛋白水平对新生儿窒息脑损伤的诊断价值

目的 探究血清泛素羧基末端水解酶L1(UCH-L1)、胶质纤维酸性蛋白(GFAP)水平对新生儿窒息后脑损伤的诊断价值.方法 选取2016年1月至2019年5月海口市第四人民医院收治的窒息新生儿126例,根据1 min Apgar评分分为重度窒息组57例和轻度窒息组69例.另根据病儿出生后5～14 d颅脑B超、CT或核磁...     

肺动脉高压中NF-κB对IL-6表达的调控作用研究

目的 研究肺动脉高压中巨噬细胞内核因子κB(NF-κB)对白细胞介素-6(IL-6)表达的调控作用.方法 选取健康雄性Sprague-Dawley大鼠24只,随机分3组,每组各8只.对照组颈背部皮下注射生理盐水1次,饲养4周;4周组、6周组颈背部皮下注射野百合碱(60 mg/kg)1次,分别饲养4周、6周.测量右心室平...     

舍曲林和氟西汀对慢性肺动脉高压模型大鼠的保护作用研究

目的:研究选择性5-羟色胺重吸收抑制剂(SSRI)舍曲林和氟西汀对野百合碱(MCT)诱导的慢性肺动脉高压(PAH)大鼠的保护作用。方法:40只大鼠随机分为对照组、MCT组、MCT+舍曲林(MCT+Ser)组和MCT+氟西汀(MCT+Flu)组,后3组大鼠腹腔注射MCT造模。MCT+Ser组和MCT+Flu组大鼠每天分别给予Ser和Flu,MCT组和对照组大鼠给予相应溶剂。各组大鼠常规饲养3周后检测肺动脉压、右心指数;HE染色法测定并计算非肌型动脉、部分肌型动脉及肌型动脉所占比例,比较各组肺动脉肌化程度;逆转录-聚合酶链反应法测定5-羟色胺转运体(SERT)mRNA表达变化。结果:与对照组比较,MCT组肺动脉压、右心指数、动脉肌化程度及SERTmRNA表达升高;与MCT组比较,MCT+Ser组和MCT+Flu组上述各指标均降低(P<0.05或P<0.01)。结论:Ser和Flu对MCT诱导的PAH具有抑制作用,作用机制可能与抑制SERTmRNA表达有关。     

氟西汀对大鼠肺动脉平滑肌细胞体外增殖的影响

目的观察氟西汀对大鼠肺动脉平滑肌细胞体外增殖的影响并探讨其可能的机制。方法采用肺动脉平滑肌细胞(PASMC)体外培养的方法,观察氟西汀对PASMC增殖及细胞周期的影响。实验细胞分为4组:①正常对照组(Control):培养液含10%胎牛血清的高糖DMEM;②5-HT组:培养液含10%胎牛血清的高糖DMEM,其中加入终浓度为5μg/mL的5-HT的培养液100μL;③Flu组:培养液含10%胎牛血清的高糖DMEM,其中加入终浓度为10μg/mL的Flu的培养液100μL;④5-HT+Flu组:培养液含10%胎牛血清的高糖DMEM,其中加入培养液100μL(其中5-HT终浓度为5μg/mL,Flu终浓度为10μg/mL)。4组细胞均在常规条件下培养,分别于实验第24、48及72小时采用MTT法测定各组细胞的吸光度值(A490),并采用流式细胞周期分析方法测定各组细胞不同时间点细胞周期分布的特点。结果 PASMC离体干预实验结果表明,5-HT+Flu组细胞随着氟西汀浓度增高或时间延长,A490较对照组逐渐降低。细胞周期分析显示,氟西汀作用于PASMC 72 h后,细胞周期分布表现为S期细胞比例下降,G0/G1期细胞比例上升。结论氟西汀可有效拮抗5-HT刺激所致的PASMC增殖,且这一作用可能与氟西汀阻碍PASMC向DNA合成期转化有关。     

神经母细胞瘤抑瘤蛋白1在肺动脉高压大鼠中的表达变化

目的研究神经母细胞瘤抑瘤蛋白1(neuroblastoma suppression of tumorigenicity 1,NBL1)在野百合碱(monocrotaline,MCT)诱导的肺动脉高压(pulmonary arterial hypertension,PAH)大鼠中表达的变化。方法将40只大鼠随机分为对照组(n=10)和MCT组(n=30)。MCT组腹腔注射MCT 60 mg·kg~(-1),对照组腹腔注射等体积生理盐水;3周、4周、5周后,检测肺组织和血浆中NBL1的变化。结果 MCT注射后3周、4周、5周,大鼠肺组织NBL1 mRNA水平分别下降了70%、81%和89%,蛋白水平分别下降了36%、78%和99%,而NBL1血浆浓度由对照组的(2.82±0.58)μg·L~(-1)分别下降为(1.90±0.55)μg·L~(-1)、(1.51±0.43)μg·L~(-1)、(0.64±0.34)μg·L~(-1),且与肺血流动力学指标及右室肥厚程度均呈明显负相关;免疫组织化学染色显示,对照组NBL1主要定位于肺小动脉,而MCT组重构肺小动脉鲜有表达;细胞实验发现,NBL1能明显抑制BMP2/4对肺动脉内皮细胞BMP信号通路的激活。结论 NBL1的表达水平在MCT诱导的PAH中逐渐降低,说明NBL1或在肺血管重构中发挥重要的作用,而其血浆水平可能是PAH潜在的生物标志物。     

三七皂苷R1对肺高压大鼠模型肺动脉的舒张作用

目的探讨三七皂苷R1(notoginsenoside R1)对慢性低氧(chronic hypoxia,CH)和野百合碱(monocrotaline,MCT)致肺高压(pulmonary hypertension,PH)大鼠模型肺动脉(pulmonary arteries,PAs)收缩效应的作用及其机制。方法清洁级♂SD大鼠随机分为3组。正常对照组;CH组:大鼠饲养于氧分压为10.0%±0.5%的密封有机玻璃箱内;MCT组:大鼠按60 mg·kg-1(BW)一次性腹腔注射20 mg·L-1的MCT。观察三七皂苷R1对两种肺高压模型大鼠PAs收缩效应的作用。结果可成功制备CH和MCT致肺高压大鼠;三七皂苷R1(0.1～100μmol·L-1)对10 nmol·L-1内皮素-1(endothelin-1,ET-1)诱发正常大鼠PAs收缩效应呈剂量依赖性舒张,EC50为(5.25±0.14)μmol·L-1;3 nmol·L-1Gd3+阻断ET-1诱发两种肺高压模型大鼠PAs收缩效应后,再加入三七皂苷R1无进一步抑制作用;6μmol·L-1三七皂苷R1对环匹阿尼酸(cyclopiazonic acid,CPA)诱发两种肺高压模型大鼠PAs收缩效应均有明显的抑制作用。结论三七皂苷R1可能通过阻断钙池操纵性钙内流介导的PAs收缩产生治疗肺高压作用。     

天智颗粒联合长春西汀治疗脑梗死恢复期的临床研究

目的 探讨天智颗粒联合长春西汀注射液治疗脑梗死恢复期的临床疗效.方法 选择2019年9月—2020年9月在河南省直第三人民医院治疗的82例脑梗死恢复期患者,根据入院先后分为对照组(41例)和治疗组(41例).对照组静脉滴注长春西汀注射液,初始剂量20 mg加入生理盐水500 mL,根据病情增至30 mg,1次/d.治疗...     

鲁斯可皂苷元对野百合碱诱导的肺动脉高压大鼠炎症反应的影响

目的研究鲁斯可皂苷元(ruscogenin,RUS)对野百合碱(monocrotaline,MCT)诱导的肺动脉高压(pulmonary arteryhypertension,PAH)大鼠炎症反应的影响。方法将36只清洁级SD大鼠随机分为对照(Control)组、MCT组、RUS+MCT(RUS)组(每组12只)。MCT组及RUS组大鼠给予MCT 60 mg.kg-1腹腔注射1次,第1～21天,RUS组每天给予RUS 0.4 mg.kg-1灌胃,Control组和MCT组给予相同量溶剂灌胃。第22天测量各组大鼠体重、平均肺动脉压(mPAP),HE染色观察肺小动脉血管壁病理变化,酶联免疫吸附法(ELISA)测定第各组大鼠外周血及肺组织炎症因子白细胞介素-1β(IL-1β)的含量,ED1+单核细胞免疫组化测定肺小动脉周围单核细胞的浸润。结果 RUS可抑制MCT诱导的大鼠mPAP升高、肺动脉壁(pulmonary aterial wallthickness,PAWT)增厚、肺动脉周围单核细胞浸润,降低大鼠外周血及肺组织IL-1β的水平。结论 RUS可能通过抑制肺血管炎症反应、降低肺动脉压及肺小动脉厚度防治肺动脉高压。     

氟西汀对大鼠海马脑源性神经营养因子基因表达的作用

目的　为了进一步探讨抗抑郁药作用的分子机制。方法　采用原位杂交技术 (地高辛标记的BDNFcDNA探针 )检测长期给予抗抑郁药氟西汀及生理盐水大鼠海马神经元BDNFmRNA的表达。结果　与生理盐水组相比 ,氟西汀组表达增强 ,尤以CA3、CA1区为甚。结论　长期给药后脑内有关区域BDNF表达改变可能是抗抑郁效应发生的受体后分子作用机制之一     

分泌型簇蛋白在肺动脉高压大鼠中的表达变化

目的探讨分泌型簇蛋白(secretory clusterin,sCLU)在野百合碱(monocrotaline,MCT)诱导肺动脉高压(pulmonary arterial hypertension,PAH)大鼠肺组织和血浆中的表达变化。方法 30只♂Sprague Dawley(SD)大鼠随机分为对照组(n=6)和MCT组(n=24),MCT组给予腹腔注射60 mg·kg-1MCT,对照组(n=6)注射同体积的生理盐水。分别检测注射MCT后1、2、3、4周大鼠肺组织中sCLU的mRNA和蛋白质水平的表达变化、sCLU在肺血管中的定位情况及血浆中sCLU浓度的变化。结果 sCLU的mRNA和蛋白表达在MCT组大鼠肺组织中呈时间依赖性的明显升高,并且其主要定位于重构肺小动脉的胞质及细胞外基质中;sCLU的血浆浓度随PAH的进展而逐渐升高,且其与肺血流动力学指标及右室肥厚指数均呈正相关。结论 sCLU在MCT诱导PAH大鼠的肺组织和血浆中表达明显升高,它可能在肺血管重构过程中发挥着重要的作用,并可能是反应PAH严重程度的生物标志物。     

Role of phosphodiesterases in adult-onset pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is characterized by increased mean pulmonary artery pressure (mPAP) due to vasoconstriction and structural changes in the small pulmonary arteries (PAs); proliferation of pulmonary artery smooth muscle cells (PASMCs) contributes to the remodeling. The abnormal pathophysiology in the pulmonary vasculature relates to decreased cyclic nucleotide levels in PASMCs. Phosphodiesterases (PDEs) catalyze the hydrolysis of cAMP and cGMP, thereby PDE inhibitors are effective in vasodilating the PA and decreasing PASMC proliferation. Experimental studies support the use of PDE3, PDE5, and PDE1 inhibitors in PAH. PDE5 inhibitors such as sildenafil are clinically approved to treat different forms of PAH and lower mPAP, increase functional capacity, and decrease right ventricular hypertrophy, without decreasing systemic arterial pressure. New evidence suggests that the combination of PDE inhibitors with other therapies for PAH may be beneficial in treating the disease. Furthermore, inhibiting PDEs in the heart and the inflammatory cells that infiltrate the PA may offer new targets to reduce right ventricular hypertrophy and inhibit inflammation that is associated with and contributes to the development of PAH. This chapter summarizes the advances in the area and the future of PDEs in PAH.     

Role of the endothelium in pulmonary arterial hypertension

Pulmonary hypertension represents a significant disease burden in both the developed and developing worlds. Certain forms of pulmonary hypertension are more common in some countries than others but people of all races, all ages and both sexes are affected. Treatment options are limited and expensive. The development of new therapies will be determined by improved understanding of endothelial cell biology.     

Role of the serotonin transporter in pulmonary arterial hypertension

Pulmonary arterial hypertension is a disease in which pulmonary arterial pressure is raised, leading to right heart failure. Survival is poor despite current therapeutic strategies. The ‘serotonin hypothesis of pulmonary arterial hypertension’ arose in the 1960s following an ‘epidemic’ of pulmonary arterial hypertension in women taking the indirect serotinergic agonist aminorex as an anorexigen. In the 1980s, the hypothesis was revisited following the occurrence of pulmonary arterial hypertension associated with the use of fenfluramines as anorexigens; these are also indirect serotinergic agents. Research has identified changes in serotonin synthesis, serotonin receptor activation and serotonin uptake via the serotonin transporter in experimental and clinical pulmonary arterial hypertension. This review will discuss our current understanding of this serotonin hypothesis with particular reference to the role of the serotonin transporter.     

三七皂苷R1对肺高压大鼠肺动脉平滑肌细胞SOCE的抑制作用

目的探讨三七皂苷R1(notoginsenoside R1)对慢性低氧(chronic hypoxia,CH)及野百合碱(monocrotaline,MCT)致肺高压(pulmonary hypertension,PH)大鼠肺动脉平滑肌细胞(pulmonary arterial smooth muscle cells,PASMCs)钙池操纵性钙内流(store-operated calcium entry,SOCE)的作用。方法制备CH及MCT致PH大鼠模型,通过Mn2+淬灭Fura-2荧光和Fluo-3荧光检测胞质游离Ca2+浓度(intracellular free calcium concentration,[Ca2+]i)观察三七皂苷R1对CH及MCT致PH大鼠PASMCs SOCE的作用。结果成功制备CH及MCT致PH大鼠模型;在硝苯地平预处理情况下,10μmol·L-1三七皂苷R1可明显降低环匹阿尼酸(cyclopiazonic acid,CPA)诱导CH及MCT致PH大鼠PASMCs Mn2+淬灭幅度、Mn2+最大淬灭率、胞膜Ca2+内流量和静息[Ca2+]i。结论三七皂苷R1对CH及MCT致PH大鼠PASMCs具有抑制SOCE和降低静息[Ca2+]i的作用。     

Effects of nicorandil on monocrotaline-induced pulmonary arterial hypertension in rats

We investigated whether nicorandil might prevent and reverse monocrotaline (MCT)-induced pulmonary arterial hypertension. Rats were injected with 50 mg/kg of MCT subcutaneously and randomized to either 7.5 mg/kg/d of nicorandil in drinking water or placebo for 3 weeks. Animals that were treated with MCT and survived for 3 weeks were assigned to either nicorandil or placebo. Nicorandil markedly attenuated pulmonary arterial hypertension with severe structural remodeling of the pulmonary vessels. The survival rate at 3 weeks after treatment was significantly increased in the nicorandil group compared with the placebo group (73% versus 39%, P<0.05). In the placebo group, endothelial nitric oxide synthase (eNOS) protein was significantly decreased, the numbers of the CD45-positive cells and those of the proliferating cell nuclear antigen-positive cells were increased in the lung tissue, and P-selectin was intensely expressed on the endothelium of the pulmonary arteries. These features were prevented by nicorandil. Late treatment with nicorandil did not palliate established pulmonary arterial hypertension nor improved survival. Thus, nicorandil inhibited development of MCT-induced pulmonary arterial hypertension but failed to reverse it. These effects were associated with marked up-regulation of diminished lung eNOS protein along with improvement of pulmonary vascular endothelial activation and anti-inflammatory and anti-proliferative effects in the lung tissue.