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1.
黄连素对COPD大鼠气道炎症和粘液高分泌的调控作用研究   总被引:2,自引:0,他引:2  
目的探讨黄连素对COPD大鼠气道炎症和粘液高分泌的影响及研究其相关分子机制。方法清洁级雄性Wistar大鼠随机分为生理盐水对照组、COPD模型组和黄连素组各10只,通过熏香烟加气管注内毒素方法建立大鼠COPD模型。采集支气管肺泡灌洗液用ELISA法检测中性粒细胞弹性蛋白酶(neutrophil elastase,NE)、IL-10含量。采集支气管-肺组织标本用免疫组织化学法(SP法)检测NF-κB、粘蛋白Muc5ac表达,采用逆转录-聚合酶链反应(RT-PCR)检测Muc5ac mRNA表达。结果 COPD模型组大鼠BALF细胞总数、中性粒细胞数(PMN)、巨噬细胞数(AM)、NE较正常对照组显著升高(P〈0.01),IL-10水平显著下降(P〈0.01)。黄连素组BALF细胞总数、PMN、AM较COPD组显著降低(P〈0.01),L-10水平升则高(P〈0.05)。COPD模型组大鼠气道黏膜上皮NF-κB、Muc5ac mRN及蛋白表达较正常对照组显著升高(P〈0.01)。黄连素组气道黏膜上皮NF-κB、Muc5ac mRN及蛋白表达较COPD组显著下降(P〈0.01)。结论黄连素可负向调节气道炎症和粘液高分泌,其机制可能与黄连素抑制NE、NF-κB炎症因子,促进抗炎因子IL-10,下调粘蛋白Muc5ac表达有关。  相似文献   

2.
氯胺酮对内毒素诱导大鼠急性肺损伤的影响及其机制   总被引:2,自引:2,他引:0  
目的探讨不同剂量氯胺酮对内毒素(LPS)诱导大鼠肺损伤的影响和作用机理。方法48只雄性Wistar大鼠随机分为4组:对照组,LPS组(5mg/kg),低剂量氯胺酮治疗组(5mg/kg),高剂量氯胺酮治疗组(10mg/kg),每组12只。建立内毒素诱导的大鼠急性肺损伤模型,于注射LPS后4h处死大鼠,测肺湿/干重比,观察支气管肺泡灌洗液(BALF)中性粒细胞计数比、蛋白浓度,测肺组织中肿瘤坏死因子α(TNF-α)、白细胞介素-8(IL-8)、NO水平。RT.PCR测肺组织中.NOSmRNA表达,Western-blot测肺组织中NF-κB蛋白表达。结果LPS组大鼠肺湿/干重比、BALF中性粒细胞计数比、蛋白浓度均明显增加(P〈0.01),肺组织中TNF-α、IL-8、NO水平显著性升高(P〈0.01),同时肺组织中iNOSmRNA和核因子-κB(NF-κB)蛋白表达均增加。而氯胺酮治疗组的各项指标均较LPS组减轻,大剂量组作用更明显。结论氯胺酮通过抑制NF-κB表达,减少炎症性细胞因子的产生,从而对内毒素(LPS)诱导的大鼠肺损伤有一定保护作用。  相似文献   

3.
目的:探讨细胞外信号通路1/2(ERK1/2)在气道黏液高分泌过程中的作用。方法:通过大鼠气道内注入脂多糖(LPS)并烟熏建立气道黏液高分泌模型。分别给予ERK1/2特异性阻断剂-U01260.25mg/kg、0.5mg/kg和1mg/kg腹腔注射14d。提取肺组织,采用免疫组化、RT-PCR等方法检测Muc5ac、ERK1/2及磷酸化ERK1/2(p-ERK1/2)等的表达水平。结果:LPS及烟熏刺激可以使大鼠气道上皮Muc5ac mRNA和蛋白的表达增多,并引起p-ERK1/2与ERK1/2比值明显增高。U0126可以抑制由LPS导致的气道Muc5ac高表达和p-ERK1/2与ERK1/2比值增高。p-ERK1/2与ERK1/2的比值与Muc5ac mRNA和蛋白的表达呈正相关关系。结论:U0126可抑制LPS及烟熏所致的气道黏液高分泌状态,其机制可能是ERK1/2信号通路参与了气道黏液高分泌的调控,U0126通过特异性阻断ERK1/2从而导致黏液高分泌的下调。  相似文献   

4.
朱卫国  靳艳华  白小红  陈莉  顾大勇 《四川医学》2005,26(12):1393-1396
目的 探讨脂多糖(LPS)的直接诱导作用对肺微血管内皮细胞(PMVEC)IL-8表达的影响及通过核因子κB(NF-κB)的调控机制。方法 以100ng/ml LPS刺激PMVEC 0、0.5、1、2、4、6、8h或1ng/ml、10ng/ml、100ng/ml LPS刺激1h或6h为检测时相点,ELISA、原位杂交试验分别检测的培养液上清中分泌的IL-8及PMVEC内IL-8mRNA的表达;凝胶电泳迁移率分析(EMSA)检测NF-κB的活化;并观察NF-κB活化抑制对IL-8表达的影响。结果 LPS能显著促进PMVEC表达IL-8,包括促进IL-8mRNA的表达及IL-8的分泌。在时间上mRNA的表达先于IL-8分泌。且LPS的直接诱导能迅速活化NF-κB,1h达到高峰,后逐渐下降。PDTC能显著抑制NF-κB的活化及IL-8的表达(P〈0.01)。结论 表明细茵致病因子LPS的直接诱导确能通过促进NF-κB的活化,从而启动IL-8的高效表达和分泌,为多形核中性粒细胞(PMN)的迁移提供必需的物质条件,导致肺损伤。  相似文献   

5.
目的 观察哮喘小鼠吸入脂多糖 (LPS,作为刺激原)其气道炎症和气道黏液分泌的变化 。 方法 30只清洁级BALB/c小鼠随机分为哮喘组 (AST组)、LPS哮喘组 (LAS组)和正常组 (NS组),每组10只。哮喘组用卵清白蛋白 (OVA)致敏和激发制作哮喘模型,LPS哮喘组在哮喘模型的基础上加用LPS (50 μg/mL)雾化吸入30 min,正常组用生理盐水代替OVA。检测各组小鼠支气管肺泡灌洗液 (BALF)细胞总数和细胞分类计数,采用ELISA检测BALF中的白细胞介素4 (IL-4)和肿瘤坏死因子-α (TNF-α)水平,HE染色观察肺部病理学改变,用阿尔辛蓝-过碘酸雪夫 (AB-PAS)染色气道杯状细胞,免疫组织化学法检测肺组织中黏蛋白5ac (Muc5ac)的表达,荧光定量RT-PCR检测Muc5ac mRNA在肺内的表达。并分析Muc5ac蛋白表达与各指标的相关性。 结果 AST及LAS组小鼠较NS组在BALF中的细胞总数、嗜酸性粒细胞、单核细胞、淋巴细胞百分比,IL-4和TNF-α水平、肺组织AB-PAS阳染面积, Muc5ac蛋白和mRNA表达明显升高,其差异均有统计学意义 (P均<0.05)。LAS组较AST组上述气道炎症(除单核细胞数外)和气道黏液高分泌指标明显增高,差异均有统计学意义 (P<0.05)。气道Muc5ac蛋白表达与BALF中细胞总数、嗜酸性粒细胞数、IL-4、TNF-α水平、气道AB-PAS染色阳性着色面积均呈正相关(P均<0.05)。 结论 OVA致敏和激发的哮喘小鼠出现以嗜酸性粒细胞、淋巴细胞浸润为主的气道炎症及杯状细胞增生的气道黏液高分泌,且气道炎症和气道黏液高分泌关系密切。LPS可使气道炎症和气道黏液高分泌加重,可能与LPS激发了体内炎症介质的生成、活化有关。  相似文献   

6.
目的 探讨消退素RvD1对脂多糖 (LPS)诱导的胰腺腺泡细胞(AR42J)炎性效应的干预作用,并分析其机制。方法 将AR42J细胞分为6组:RvD1(100 nmol/L)组,LPS组, RvD1 (1、10、100 nmol/L)+LPS组和生理盐水对照组。其中LPS组和RvD1+LPS组以100 mg/L LPS刺激AR42J细胞,构建急性胰腺炎的体外模型,RvD1+LPS组在建模前先用不同浓度 (1、10、100 nmol/L)RvD1对AR42J细胞预处理30 min。实时荧光定量PCR检测各组AR42J细胞TNF-α、IL-6、及NF-κB活性亚基p65的mRNA表达;ELISA检测培养液上清中TNF-α、IL-6蛋白浓度的改变;流式细胞术检测AR42J细胞的NF-κB激活率。结果 RvD1可以抑制LPS诱导的AR42J炎症细胞因子TNF-α、IL-6 mRNA及蛋白的表达, 且呈剂量依赖方式。RvD1同样以剂量依赖方式抑制LPS诱导的AR42J细胞p65 mRNA表达及NF-κB激活率。结论 RvD1可以呈剂量依赖方式抑制LPS诱导的腺泡细胞NF-κB激活,进一步抑制TNF-α、IL-6等细胞因子的分泌,从而抑制胰腺腺泡细胞的炎性反应。  相似文献   

7.
依拉普利对丙烯醛诱导的气道炎症干预作用的研究   总被引:1,自引:1,他引:0  
目的应用丙烯醛建立气道炎症模型,给予依拉普利进行干预,了解其对气道炎症的影响,并探讨核因子(NF-κB)在这一过程中的作用。方法健康雄性SD大鼠24只,随机分为4组,每组6只。A组:空白对照组(吸入生理盐水);B组:依拉普利自身对照组(单纯依拉普利灌胃),依拉普利0.5mg/(kg.d)灌胃;C组:模型组(丙烯醛),大鼠吸入4mg/L丙烯醛,每次3h,每天两次;D组:依拉普利干预组(吸入丙烯醛 依拉普利灌胃),处理同模型组,并给予依拉普利0.5mg/(kg.d)灌胃。21d后处死大鼠,采集标本。采用免疫组化方法检测肺组织中血管紧张素和气道上皮NF-κB p65的表达,并计算NF-κB p65的入核率。采用Western blot方法检测肺组织胞浆中的NF-κB。收集支气管肺泡灌洗液,检测其中的中性粒细胞数,用ELISA的方法检测TNF-α、IL-8。结果免疫组化结果显示模型组大鼠肺组织中AngⅡ、NF-κB p65的表达,NF-κB p65入核率较空白对照组明显增高,依拉普利干预组各项指标较模型组明显减少。Western blot检测发现细胞浆中NF-κB的表达量显著增高(P<0.05),依拉普利干预可以使NF-κB p65的表达有一定程度的降低(P<0.05)。支气管肺泡灌流液(BALF)中中性粒细胞数以及ELISA检测的BALF中的炎性细胞因子IL-8和TNF-α模型组显著高于对照组,依拉普利干预组中均有明显降低(P值均<0.05)。结论在丙烯醛诱导的气道和肺的炎症模型中,AngⅡ起了重要的作用,依拉普利可部分抑制这一炎症反应,其机制可能与它抑制了NF-κB的激活有关。  相似文献   

8.
目的观察不同剂量卡维地洛对培养的健康人外周血单个核细胞(peripheral blood mononuclear cell,PB-MC)在脂多糖(lipopolysaccharide,LPS)刺激下分泌细胞因子(TNF-α、IL-1、IL-6)的变化,并测定单个核细胞核因子-κB(nuclear factor-κB,NF-κB)活化程度,探讨卡维地洛的心血管保护作用,为卡维地洛的临床应用提供理论依据。方法抽取15例健康体检者空腹肘静脉血各5ml,分离单个核细胞,在含10%胎牛血清的RPMI-1640培养基悬浮细胞。应用放射免疫法测定培养上清液中IL-1β、IL-6和TNF-α水平,并将单个核细胞离心涂片并固定后测定NF-κB细胞率。结果不同剂量卡维地洛对人PBMC IL-1β、IL-6和TNF-α的分泌及NF-κB活化均有不同程度抑制作用。外周血单个核细胞NF-κB阳性细胞率与培养上清液中细胞因子IL-1β、IL-6、TNF-α水平有显著正相关。结论卡维地洛能有效降低外周血单个核细胞在脂多糖刺激下细胞因子水平及NF-κB的活化,其作用具有剂量依赖性。卡维地洛降低细胞因子水平,可能是通过抑制NF-κB这一途径来实现的。这可能是其心脏保护作用机制之一。  相似文献   

9.
目的 研究护肾固精方(Hu shen gu jing fang,HSGJF)对脂多糖(LPS)刺激大鼠肾小球系膜细胞(MeasangialCells,MsC)表达炎性细胞因子的影响及其作用机制。方法:分别以酶联免疫吸附法(ELISA)检测MsCIL-1β、TNF-α蛋白水平:电泳迁移率变动分析(EMSA)检测MCs核因子-κB(nuclearfactor-κB,NF-κB)的活性;反转录多聚酶链反应技术(RT-PCR)检测MsC TNF-amRNA表达。结果 HSGJF能抑制LSP刺激肾小球MsC分泌IL-1β、TNF-α蛋白质增加的同时、亦能抑制LSP刺激肾小球MsC中NF-κB活化,在HSGJF作用下炎性细胞因子表达均呈不同程度减弱。结论 HSGJF通过抑制MsCNF-κB的活性,下调炎性细胞因子的表达。为进一步认识和评价中医药在肾脏疾病防治中的作用提供了理论及实验依据。  相似文献   

10.
气道炎症是哮喘的本质,炎细胞浸润是哮喘的发病基础,细胞因子IL-4、IL-5可诱导、维持一定的IgE水平,活化嗜酸性粒细胞(EOS)并防止其凋亡,在哮喘病理进程中发挥重要作用;核因子κB(NF-κB)是一个具有广泛生物学活性的核转录因子。它的激活可诱导以上细胞因子的表达,引发气道炎症。银杏叶有润肺、平喘的作用,是治疗哮喘的传统中药,  相似文献   

11.
Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P < 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (>0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P <0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P < 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.  相似文献   

12.
Objective: To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods: SD rats served as both donors and recipients. 4℃ sodium lactate Ringer's was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava (IVC) inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results: Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion: This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.  相似文献   

13.
Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P< 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P< 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.  相似文献   

14.
目的:评价使用安心颗粒对急诊经皮冠状动脉介入术(PPCI)术后生活质量的影响.方法:将160例接受PPCI的急性ST段抬高型心肌梗死患者随机分为安心颗粒组(术前顿服安心颗粒8.8g,术后安心颗粒4.4 g/次,每日2次)和对照组(仅接受基础药物治疗).所有患者均服用阿司匹林、氯吡格雷和阿托伐他汀.分别在入院时、出院前1d、出院后180 d时,应用心肌梗死多维度量表(MIDAS)、中文版SF-36评价量表对患者生活质量评分.并观察术后30 d以内的出血并发症、血小板减少症发生情况.结果:入院时和出院前1d,两组患者的心肌梗死MIDAS、SF-36量表评分比较无差异(P>0.05);出院后180 d时,与对照组比较,安心颗粒组MIDAS、SF-36评分明显减低(P<0.05);组内与入院时比较,两组出院前1d、出院后180 d时,MIDAS、SF-36评分均降低(P<0.05).两组患者在随访期间均无大量出血、少量出血、重度和极重度血小板减少症发生,安心颗粒组有4例、对照组有7例发生不明显出血(P>0.05).两组发生轻度血小板减少症的患者数比较无差异(P>0.05).结论:PPCI使用安心颗粒,能改善急性ST段抬高型心肌梗死患者的生活质量,且不增加出血风险.  相似文献   

15.
Objective:To investigate the influences of urapidil and nicardipine on rabbit sinus function,atrio-ventricular node function and hemodynamics.Methods:Thirty-two Angora's rabbits were selected and randomly divided into four groups.U1 group:urapidil 0.25 mg/kg;U2 group:urapidil 0.5 mg/kg;N1 group:nicardipine 10 μg/kg;N2 group:nicardipine 20 μg/kg.All these medicine were administrated within 30 seconds.Measurements were taken before and after the administration of urapidil or nicardipine for the following data:mean blood pressure(MAP),heart rate(HR),sino-atrial conduction time(SACT),maximal sinoatrial recovery time(SNRTmax)corrected sinus node recovery time(CSNRT),index of sinus node recovery time(SNRTI),Wenckebach A-V conduction frequency (WB),and P-R interval.Results:Significant MAP and HR changes were identified in all of the four groups before and after administration of both urapidil and nicardipine.No significant changes could be found in the rest of the parameters.Intergroup analysis showed that SACT and CSNRT of N1 and N2 groups were shorter than those of the U2 group(P<0.01);the MAP decreased(P<0.01)and the HR increased drastically(P<0.01).Conclusions:Neither urapidil(0.25 mg/kg,0.5 mg/kg)nor nicardipine(10μg/kg,20μg/kg)has any significant influence on rabbit sinus function or rabbit atrio-ventricular node function.Nicardipine could be a better choice than urapidil for parafunctional sinus node patients.  相似文献   

16.
Objective:To investigate the gene expression of osteoprotegerin(OPG) and osteoclast differentiation factor(ODF) in the bone tissue of patients with hip fracture due to osteoporosis. Methods:OPGmRNA and ODFmRNA in the bone tissue in 50 cases of osteoporosis sufferers(over 50 years old) with hip fracture(Observer Group) and 30 cases of hip facture sufferers with no osteoporosis(Control group) were analyzed with the Semi-Quantitative RT-PCR method. Results:The mRNA expressed of ODF, OPG were both high in the patients with hip fracture. In the control group, the expression of OPG mRNA was observed, while the expression of ODF mRNA was very slight. Conclusion:Aged patients contained all signals including OPG, ODF that are essential for inducing osteoclastogenesis and promoting bone resorption.  相似文献   

17.
Objective:To investigate the clinical features, pathological characteristics and immunophenotype of solid-pseudopapillary tumor of the pancreas(SPTP). Methods:Nine surgically treated cases of SPTP were retrospectively reviewed. Hematoxylin and Eosin(HE) staining and immunohistochemical staining were used to analyze all cases, and the general clinical data was collected. Results:Six patients were asymptomatic except for a palpable mass. Two patients complained of vague-epigastric pain. One patient appeared jaundice. The tumor was encapsulated and solid tissues alternately with cystic tissues. Histologically, the histological structure of solid portion was pseudopapillary with a fibrovascular core. Tumor cells were uniform and medium-sized which were arranged in sheets ets or nests or pseudopapillary patterns. Immunohistochemical studies demonstrated that SPTP proved positive in vimentin(9/9 cases), AAT(9/9 cases), NSE(9/9 cases), ACT(7/9 cases), CK20(2/9 cases), CgA(1/9 cases), S-100(3/gcases), PR(4/gcases), Syn(3/9 cases) and CD56(5/9cases), negative in CEA and ER. Conclusion:SPTP is a tumor predominantly occurring in young women frequently without special symptoms. This tumor has various characteristical histological patterns with different immunophenotype.  相似文献   

18.
Objective:To probe into the influence of changes of ovarian hormones on the pathogenesis of the specific sub-type premenstrual syndrome(PMS)and reveal partial microcosmic mechanisms of adverse flow of liver-qi.Methods:Estradiol(E2)and progesterone(P)levels in serum were determined at different phases of menstrual cycle by radioimmunoassay.Results:In the group of PMS with adverse flow of liver-qi.the secretive peak value Of E2 and P at the follicular phase significantly decreased,and the secretive peak value at the luteal phase did not come into being.Conclusions:Low E2 and P secretive peak at the follicular phase and absence of secretive peak at the luteal phase is one of the microcosmic mechanisms of PMS with adverse flow of liver-qi.One of the pathophysiologic mechanisms of specific sub-type PMS is probably the continuous low level of E2and P.  相似文献   

19.
Real-time three-dimensional echocardiography (RT3DE)is a new ultrasound technique that enables dynamic threedimensional visualization and quantification of the heart in real time. Investigation of feasibility and methodology of RT3DE in determining left ventricular (LV) and right ventricular (RV) volumes, RT3DE was performed in 35 normal adults using Philips SONOS 7500 system with a 2-4 MHz matrix array transducer. The 60°×60° "pyramid" volume database was obtained and analyzed on a TomTec echo workstation. Both LV and RV volumes were calculated with four 3DE methods (i.e. apical 2, 4, 8, and 16-plane) through manually tracing ventricular endocardial borders in end diastole and end systole. Stroke volumes were then calculated. LV volume was also measured by 2DE Simpson's rule using GE VIVID 7 ultrasound machine.  相似文献   

20.
Increasing maternal age is the only etiological factor unequivocally linked to Down's syndrome in humans. The occurrence rate of newborns with Down's syndrome is about 1/220 in women over 35 years old. However, the occurrence rate in embryos fertilized in vitro, of the elder woman is unclear. Using FISH we screened the number of chromosome 21 in preimplanted embryos of 5 elderly women (average age, 38.4 years) to study the feasibility and necessity of screening trisomy 21 in embryos in patients over 35 years old at the in vitro fertilization (IVF) center.  相似文献   

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