阻塞性睡眠呼吸暂停低通气综合征患者手术前后血中CRP、TNF-α、IL-8的变化

目的探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者手术前后血中C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、白细胞介素-8(IL-8)水平的变化。方法选取67例经多导睡眠监测仪(PSG)证实的重度OS-AHS患者作为研究组,同时以30例与研究对象相匹配的健康人群做对照。用放射免疫法检测血清中TNF-α及IL-8,用乳胶增强免疫比浊法检测血清中CRP。结果术前OSAHS组血清CRP〔(7.01±0.33)mg/L〕、TNF-α〔(1.82±0.36)μg/L〕、IL-8〔(227.18±88.17)ng/L〕水平明显高于对照组〔(2.87±0.21)mg/L、(0.99±0.31)μg/L、(153.23±62.11)ng/L〕(P均<0.05);术后OSAHS组血清CRP〔(3.27±0.33)mg/L〕、TNF-α〔(1.11±0.27)μg/L〕、IL-8〔(149.73±66.12)ng/L〕水平较术前明显下降(P均<0.05),与对照组水平比较差异无统计学意义(P均>0.05)。结论 OSAHS患者术前血清中CRP、TNF-α、IL-8水平失衡,经过鼻持续正压通气及手术治疗后,3种因子水平可下降至正常水平。CRP、TNF-α及IL-8可做为OSAHS诊治的有效指标。     

蜂胶对慢性阻塞性肺疾病患者肺泡巨噬细胞胞浆游离钙浓度及其生成细胞因子的影响

目的:观察蜂胶对慢性阻塞性肺疾病患者(chronicobstructivepulmonarydisease,COPD)肺泡肺泡巨噬细胞(alveolarmacrophage,AM)游离钙浓度及其生成的白细胞介素8(IL-8)、一氧化氮的影响。方法:采用支气管肺泡灌洗、细胞培养和荧光指示剂方法,测定AM内钙浓度其生成的IL-8和NO。结果:COPD组患者AM内钙浓度犤(68.26±7.24)nmol/L犦,IL-8犤(29.11±9.78)ng/L犦,一氧化氮犤(27.61±8.64)μg/L犦均高于对照组犤(60.61±6.26)nmol/L,(15.42±6.78)ng/L,(13.99±7.40)μg/L犦(t=11.38～36.42,P<0.01)。脂多糖刺激以后,胞内游离钙浓度、IL-8和一氧化氮均较刺激前增高(t=12.65～32.58,P<0.01)。先加蜂胶孵育AM再加入脂多糖,胞浆内游离钙浓度、IL-8和一氧化氮较仅加脂多糖时减少(t=14.72～25.02,P<0.01)。结论:蜂胶可抑制脂多糖引起的犤Ca2+犦i增加,对脂多糖刺激的IL-8和一氧化氮升高也有抑制作用;可调节AM激活,抑制IL-8、一氧化氮分泌。     

黄芪对慢性阻塞性肺疾病患者脂多糖引起游离钙浓度变化的影响

目的:观察黄芪对慢性阻塞性肺疾病(chronicobstructivepulmonarydis-ease,COPD)患者肺泡巨噬细胞(alveolarmacrophage,AM)胞浆游离钙浓度及其生成的肿瘤坏死因子-α(TNF-α)、丙二醛的影响。方法:COPD组:选自1996-05/11山西医科大学第二医院呼吸科门诊患者13例,其中男7例,女6例。纳入标准:均符合2002年8月中华医学会呼吸分会慢性阻塞性肺疾病诊治指南诊断标准,COPD分级为0级。排除标准:排除COPD分级为1～4级的患者。对照组:为本院门诊具有健康肺的患者13例,男8例,女5例。采用支气管肺泡灌洗、细胞培养和荧光指示剂方法,测定AM内钙浓度其生成的TNF-α和丙二醛。结果:①COPD患者AM内钙浓度(68.26±7.24)nmmol/L,TNF-α(5.74±0.42)μg/L、丙二醛(3.77±0.61)μg/L(每升1×109个AM细胞数分泌的TNF-α,丙二醛μg值)均较对照组胞内钙浓度(60.61±6.26)nmmol/L,TNF-α,丙二醛(2.06±0.20),(1.909±0.19)μg/L高(P<0.01)。②脂多糖刺激以后,胞内游离钙浓度,TNF-α,丙二醛均较刺激前增高(P<0.01)。③先加黄芪孵育AM再加入脂多糖,胞浆内游离钙浓度,TNF-α和丙二醛较仅加脂多糖时减少(P<0.01)。结论:黄芪可抑制脂多糖引起的游离钙浓度增加,对脂多糖刺激的TNF-α和丙二醛升高也有抑制作用;黄芪可调节肺泡巨噬细胞激     

稳定期慢性阻塞性肺疾病患者血浆及诱导痰中炎性因子水平变化

目的探讨稳定期慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)患者血浆及诱导痰中炎性因子水平的变化及意义。方法稳定期COPD患者201例为COPD组,根据改良呼吸困难指数(modified British Medical Research Council,mMRC)评分、COPD评估测试(COPD assessment test,CAT)评分、急性加重发作次数分为4个亚组,A组11例(mMRC评分为0～1级,CAT评分10分,急性加重发作次数0～1次),B组33例(mMRC≥2级,CAT评分≥10分,急性加重发作次数0～1次),C组32例(mMRC评分为0～1级,CAT评分10分,急性加重发作次数≥2次),D组125例(mMRC评分≥2级,CAT评分≥10分,急性加重发作次数≥2次);同期体检健康者50例为对照组。比较各组一般资料,检测各组血浆及诱导痰中白细胞介素(interleukin,IL)-1β、IL-6、IL-8、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、高敏C反应蛋白(high-sensitivity C-reactive protein,hs-CRP)水平。结果 COPD组血浆IL-6、IL-8、TNF-α水平均高于对照组(P0.05);D组血浆IL-6[(2.61±1.16)ng/L]、IL-8[(16.56±5.52)ng/L]、hs-CPR[(1 862.26±578.39)mg/L]、TNF-α[(373.39±136.24)nmol/L]水平高于C组[(2.07±0.83)ng/L、(14.06±7.26)ng/L、(1 736.19±548.37)mg/L、(380.01±128.65)nmol/L]、B组[(1.87±0.62)ng/L、(12.13±4.70)ng/L、(1 636.54±449.45)mg/L、(301.17±134.60)nmol/L]和A组[(1.69±0.43)ng/L、(9.09±2.57)ng/L、(1 602.34±390.26)mg/L、(258.14±49.48)nmol/L](P0.05),C组高于B组和A组(P0.05);COPD组诱导痰IL-6、IL-8、hs-CRP、TNF-α和IL-1β水平均高于对照组(P0.05);D组诱导痰IL-6[(289.46±131.25)ng/L]、IL-8[(1 409.29±446.95)ng/L]、hs-CRP[(3 614.89±723.25)mg/L]、TNF-α[(1 212.25±247.37)nmol/L]高于C组[(209.39±131.38)ng/L、(921.72±359.77)ng/L、(3 291.68±630.75)mg/L、(779.77±213.75)nmol/L]、B组[(194.29±77.29)ng/L、(966.63±318.65)ng/L、(3 219.12±762.31)、(1 191.50±362.56)nmol/L]和A组[(147.16±32.68)、(894.78±278.33)、(3 139.95±605.17)、(780.20±396.38)nmol/L](P0.05);A、B、C、D组诱导痰IL-1β水平比较差异均无统计学意义(P0.05)。结论稳定期COPD患者血浆及诱导痰炎性因子水平随mMRC、CAT评分增加相应增高。     

黄芪对慢性阻塞性肺疾病患者脂多糖引起游离钙浓度变化的影响

目的：观察黄芪对慢性阻塞性肺疾病(chronic obstructive pulmonary diseabe，COPD)患者肺泡巨噬细胞(alveolar macrophage，AM)胞浆游离钙浓度及其生成的肿瘤坏死因子-α(TNF-α)、丙二醛的影响。方法：COPD组：选自1996-05／11山西医科大学第二医院呼吸科门诊患者13例，其中男7例，女6例。纳入标准：均符合2002年8月中华医学会呼吸分会慢性阻塞性肺疾病诊治指南诊断标准，COPD分级为0级。排除标准：排除COPD分级为1-4级的患者。对照组：为本院门诊具有健康肺的患者13例，男8例，女5例。采用支气管肺泡灌洗、细胞培养和荧光指示剂方法，测定AM内钙浓度其生成的TNF-α和丙二醛。结果：①COPD患者AM内钙浓度(68．26&;#177;7.24)nmmol／L，TNF-α(5．74&;#177;0．42)μg／L、丙二醛(3.77&;#177;0．61)μg／L(每升1&;#215;10^9个AM细胞数分泌的TNF-αn，丙二醛μg值)均较对照组胞内钙浓度(60．61&;#177;6．26)nmmol／L．TNF-α，丙二醛(2．06&;#177;0．20)，(1．909&;#177;0.19)μg／L高(P&;lt;0．01)。②脂多糖刺激以后，胞内游离钙浓度，TNF-α，丙二醛均较刺激前增高(P&;lt;0．01)。③先加黄芪孵育AM再加入脂多糖，胞浆内游离钙浓度，TNF-α和丙二醛较仅加脂多糖时减少(P&;lt;0．01)。结论：黄芪可抑制脂多糖引起的游离钙浓度增加，对脂多糖刺激的TNF-α和丙二醛升高也有抑制作用；黄芪可调节肺泡巨噬细胞激活，抑制TNT-α丙二醛分泌。     

血清缺氧诱导因子1α和肿瘤坏死因子α及肝细胞生长因子与脑梗死的关系

目的 探讨缺氧诱导因子1α(HIF-1α)、肿瘤坏死因子α(TNF-α)及肝细胞生长因子(HGF)与脑梗死的关系.方法 入选2013年6-12月我院收治的急性脑梗死患者212例作为观察对象,根据脑梗死类型分为进展性脑梗死(PCI)组105例和稳定性脑梗死(SCI)组107例,选取同期100名健康体检人群作为对照,采用酶联免疫吸附法(ELISA)检测3组研究对象的HIF-1α、TNF-α及HGF;将PCI组患者按照神经功能或梗死病灶大小分组,比较各组间HIF-1α、TNF-α及HGF水平差异.结果 PCI组HIF-1α、TNF-α、HGF分别为(2.3±1.3) ng/L、(4.0±0.5)mg/L、(1.4±0.3)μg/L,显著高于SCI组[(1.1±0.5)ng/L、(3.1±1.3) mg/L、(0.7±0.4) μ#L]和健康对照组[(0.5 ±0.1)ng/L、(1.8±0.4)mg/L、(0.4±0.1)μ昏/L],SCI组显著高于健康对照组,差异均有统计学意义(F值分别为3.14、5.42、1.32,P均＜0.01);PCI轻度组患者HIF-1α、TNF-α、HGF分别为(0.7±0.3) ng/L、(2.9±0.3)mg/L、(0.7±0.5)μg/L,均显著低于中度组[(1.4±0.5)ng/L、(4.9±0.5)mg/L、(1.7±0.4)μg/L]和重度组[(1.4±0.5) ng/L、(4.9±0.5)mg/L、(1.9±0.4) μg/L,中度组显著低于重度组,差异均有统计学意义(F值分别为0.93、4.32、2.31,P均＜0.01);PCI小梗死灶组患者HIF-1α、TNF-α、HGF分别为(0.6 ±0.4)ng/L、(2.7 ±0.4)mg/L、(0.7±0.4)μg/L,均显著低于中梗死灶组[(1.1±0.5)ng/L、(4.4±0.5) mg/L、(1.1±0.2)μg/L]和大梗死灶组[(1.4±0.6)ng/L、(4.8±0.6)mg/L、(1.9±0.5)μg/L];中梗死灶组显著低于大梗死灶组,差异均有统计学意义(F值分别为4.71、2.09、2.45,P均＜0.01).结论 进展性脑梗死患者血清HIF-1仪、TNF-α及HGF水平明显增高,且各指标与进展性脑梗死神经功能缺损程度及梗死灶大小关系密切.     

黄芪甲苷对缺氧/复氧损伤血管内皮细胞核转录因子-κB表达的影响

目的:观察黄芪甲苷对血管内皮细胞缺氧/复氧损伤中核转录因子-κB(NF-κB)表达的干预作用。方法:人脐静脉内皮细胞原代培养,传至3代后随机分为3组。对照组:常规培养;缺氧/复氧组:先缺氧处理1 h,再复氧1 h;药物干预组:培养液中加入终浓度分别为20、40和80 mg/L的黄芪甲苷预处理,12 h后进行缺氧/复氧处理。分别用酶联免疫吸附技术、硫代巴比妥法检测细胞上清液中细胞间黏附分子-1(ICAM-1)浓度、丙二醛(MDA)含量;用免疫化学法测定血管内皮细胞NF-κB的表达。结果:与对照组比较,缺氧/复氧组细胞培养液中MDA含量、ICAM-1浓度均显著增加〔MDA(6.98±1.15)μmol/L比(2.38±0.49)μmol/L,ICAM-1(3 169.01±132.75)ng/L比(995.14±74.93)ng/L,P均<0.01〕,内皮细胞NF-κB阳性细胞率明显增强〔(58.02±12.01)%比(6.28±1.43)%,P<0.01〕。与缺氧/复氧组比较,药物干预组细胞培养液中MDA含量均明显减少(P均<0.01)、ICAM-1浓度均明显降低(P均<0.01),内皮细胞NF-κB阳性细胞率均明显降低(P<0.05或P<0.01)。结论:黄芪甲苷能显著抑制缺氧/复氧引起的血管内皮细胞NF-κB表达,且呈剂量依赖性,对缺氧/复氧损伤的血管内皮细胞具有保护作用。     

氯化镧阻断LPS诱导巨噬细胞钙信号通路激活及TNF-α释放

目的探讨氯化镧(LaCl3)对脂多糖(Lipopolysaccharide,LPS)诱导巨噬细胞钙信号通路激活及肿瘤坏死因子α(TNF-α)释放的影响。方法将巨噬细胞RAW 264.7随机分成四组:LPS组(培养液中含1μg/ml LPS),LaCl3+LPS组(以含2.5μmol/ml LaCl3的培养基孵育细胞一定时间后,再予以1μg/ml LPS刺激),LaCl3组(培养液中含2.5μmol/ml LaCl3)及对照组(培养液中不含LaCl3和LPS)。于不同时间点分别收集各组细胞及其培养上清待测。以Fluo-3/Am加载细胞,经上述不同分组处理一定时间后,流式细胞术观察细胞内Ca2+浓度([Ca2+]i)的变化;采用酶联免疫吸附试验(ELISA)检测上清中TNF-α水平。结果流式细胞术测定结果显示:LPS组细胞内[Ca2+]i为(336.67±26.16nmol/L),与对照组比较差异显著(P0.01);LaCl3+LPS组(162.67±26.41nmol/L)显著低于LPS组(P0.01);LaCl3组(29.84±6.42nmol/L)与对照组相比略低但无统计学意义(P0.05)。LPS组细胞培养上清TNF-α含量(152.19±15.68pg/ml)与对照组相比,显著升高(P0.01);而LaCl3+LPS组细胞培养上清中TNF-α含量为43.95±6.55 pg/ml,与LPS组相比显著下降(P0.01)且与对照组相比无差异;LaCl3组细胞培养上清中TNF-α含量(27.84±3.73pg/ml)与LPS组相比显著下调(P0.01),并且与对照组相比亦显著下调(P0.05)。结论一定浓度的LaCl3可阻断LPS诱导巨噬细胞钙信号通路激活及抑制TNF-α的释放。     

老年急性呼吸窘迫综合征患者血清可溶性血栓调节蛋白水平变化及临床意义

目的探讨老年急性呼吸窘迫综合征(acute respiratory distress syndrome, ARDS)患者血清可溶性血栓调节蛋白(soluble thrombomodulin, sTM)水平变化及临床意义。方法 138例老年ARDS患者(观察组),根据氧合指数分为轻度组37例,中度组50例,重度组51例,并根据28 d生存状况分为生存组68例和死亡组70例;选择同期体检健康者69例为对照组。检测入选者血清sTM、降钙素原(procalcitonin, PCT)和肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)水平。绘制ROC曲线,分析sTM、PCT和TNF-α对老年ARDS患者预后的预测价值。结果观察组血清sTM[(116.00±41.53)μg/L]、PCT[(1.38±0.51)μg/L]和TNF-α[(47.59±17.39)ng/L]水平均高于对照组[(20.34±7.62)μg/L、(0.22±0.08)μg/L、(22.63±4.31)ng/L](P0.05);轻度、中度、重度组患者血清sTM[(74.98±17.91)、(119.33±38.81)、(142.49±32.35)μg/L]、PCT[(0.74±0.37)、(1.44±0.32)、(1.78±0.23)μg/L]、TNF-α[(26.11±7.19)、(47.74±10.35)、(63.02±10.12)ng/L]水平依次增高(P0.05),生存组患者血清sTM[(89.60±26.84)μg/L]、PCT[(1.16±0.52)μg/L]、TNF-α[(41.97±16.60)ng/L]水平均低于死亡组[(141.65±37.02)μg/L、(1.59±0.40)μg/L、(53.05±16.49)ng/L](P0.05);当血清sTM、PCT和TNF-α最佳截断值分别为97.18μg/L、1.31μg/L、53.01 ng/L时,预测老年ARDS患者预后的AUC分别为0.871、0.739、0.698,灵敏度分别为0.886、0.829、0.557,特异度分别为0.706、0.674、0.779。结论老年ARDS患者血清sTM、PCT和TNF-α水平明显升高,sTM可作为预测老年ARDS患者预后的标志物。     

丙泊酚联合利血平对再灌注损伤PC12细胞保护作用的研究

目的 观察丙泊酚与利血平单用或合用对缺血/缺氧及再灌注致中枢神经元细胞损伤的保护作用及其可能机制.方法 用大鼠肾上腺嗜铬细胞瘤克隆化细胞株(PC12细胞)建立缺血/缺氧及再灌注损伤的细胞模型.实验分为缺血/缺氧及再灌注损伤(IR)组、丙泊酚(P)组、利血平(R)组、丙泊酚与利血平合用(PR)组.通过测定乳酸脱氢酶(LDH)含量及应用噻唑蓝(MTT)比色法测定存活细胞在波长570 nm处的吸光度(A)值用以判断细胞损伤程度,并观察两药单独或合用对损伤PC12细胞内游离钙离子浓度([Ca2+]I)的影响.结果 与IR组比较,丙泊酚和利血平单用或联用组均可使LDH释放量明显降低,A值升高(P<0.05或P<0.01).合用利血平(40μmol/L)后,不同浓度丙泊酚(12.4、37.3和112.0μmol/L)组LDH释放量进一步降低,A值则增高(P均<0.05).12.4μmol/L和37.3μmol/L丙泊酚以及40μmol/L利血平均可减轻由于缺血/缺氧及再灌注损伤引起的细胞内钙超载[(279.66±18.00)nmol/L比(219.41±12.53)nmol/L,(279.66±18.00)nmol/L比(210.50±11.03)nmol/L,(279.66±18.00)nmol/L比(254.82±10.45)nmol/L,P<0.05或P<0.01];12.4/μmol/L和37.3μmol/L丙泊酚分别与40μmol/L利血平合用时,[Ca2+]I进一步降至(1 91.19±10.36)nmol/L和(183.82±9.83)nmol/L,与相同浓度丙泊酚组比较差异均有统计学意义(P均<0.05).结论 丙泊酚和利血平均对缺血/缺氧及再灌注损伤PC12细胞产生一定的保护作用,合用时保护作用更明显;其保护作用可能与减轻细胞内钙超载有关.     

细胞内钙与K562/A02细胞多药耐药相关性的研究

本研究旨在探讨白血病耐药细胞的发生及其逆转机制与细胞内钙离子浓度的关系。用甲基四唑蓝法(MTT)测定柔红霉素 (daunomycin ,DNR)的细胞毒性 ,用Fura 2 /AM方法测定耐药细胞株K5 6 2 /A0 2及其敏感株K5 6 2的静息 [Ca2 ]i水平 ,并观察了柔红霉素及耐药调节剂汉防己甲素 (Tetrandrine,Tet)、屈洛昔芬 (droloxifene,DRL)单独或联合应用后细胞内游离钙离子浓度的变化。结果表明 :1μmol/LTet,5 μmol/LDRL均能增加DNR对耐药细胞系K5 6 2 /A0 2的细胞毒作用 ,IC50 (半数抑制量 )分别为 ( 7.2 8± 2 .0 6 ) μg/ml,( 7.5 8± 3.4 4 ) μg/ml,逆转倍数为 2 .94和 2 .82倍。两药联合作用明显增强 ,IC50 为 ( 1.6 6± 0 .4 1) μg/ml,逆转倍数达 12 .9倍。静息状态下K5 6 2 /A0 2细胞的游离钙离子浓度显著高于K5 6 2细胞。 1μmol/LTet,5 μmol/LDRL单独作用于K5 6 2 /A0 2细胞引起 [Ca2 ]i的明显升高 ,两者联合应用有拮抗作用。结论 :K5 6 2 /A0 2细胞内Ca2 浓度的增高可能是导致其耐药的原因之一 ,但耐药调节剂Tet,DRL对耐药细胞 [Ca2 ]i的影响在其逆转耐药中的作用有待进一步研究     

Determination and clinical implication of leukotriene B(4) and tumor necrosis factor-alpha in condensate of exhaled breath of chronic obstructive pulmonary disease patients.]

OBJECTIVE: To study the changes and clinical implication of leukotriene B(4) (LTB(4)) and tumor necrosis factor-alpha (TNF-alpha) in exhaled breath condensate (EBC) of chronic obstructive pulmonary disease (COPD) patients. METHODS: EBC of 20 patients in acute episode of COPD (AECOPD), 20 patients in period of remission of COPD, and 20 persons who were having regular check-up (healthy control group) were enrolled. The concentrations of LTB(4) and TNF-alpha in EBC were assayed. Forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) of COPD patients were observed at the same time, pH, oxygenation index (PaO(2)/FiO(2)), partial pressure of oxygen in arterial blood (PaO(2)) and leukocyte count were also determined. RESULTS: (1)The concentrations of LTB(4) in EBC of AECOPD (35.43+/-14.19)ng/L and remission of COPD(24.39+/-13.75)ng/L, were significantly higher than that of the healthy control group (16.75+/-7.44)ng/L, and the concentration of LTB(4) in EBC during remission of COPD was significantly lower than that of AECOPD (all P<0.05). (2)The concentration of TNF-alpha in EBC of AECOPD (9.35+/-8.66) ng/L was significantly higher than that of remission of COPD (4.42+/-4.11)ng/L and healthy control group (4.45+/-3.92) ng/L, and the differences had statistical significance (both P<0.05). The concentration of TNF-alpha in EBC showed no significant difference between patients in remission of COPD and healthy control group. (3)The concentration of LTB(4) in EBC had negative correlation with FEV1 of AECOPD patients. Regression equation was y=-0.51x+0.22, r=-0.481 (P<0.05). CONCLUSION: The concentrations of LTB4 and TNF-alpha in EBC of AECOPD patients are raised when oxidation stress is reinforced, and its level reflects the severity and prognosis of COPD.     

酪氨酸激酶和磷酸酶及蛋白激酶C在As2O3调控NB4细胞和皮层神经元凋亡中的作用

目的　研究蛋白酪氨酸激酶和蛋白酪氨酸磷酸酶及蛋白激酶C(PKC)在三氧化二砷 (As2O3 )调控白血病细胞和人脑皮层神经元凋亡中的作用 ,观察As2 O3 对人脑皮层神经元和白血病细胞的胞浆游离钙 ([Ca2 ]i)浓度的影响。方法　用Fluo 3/AM荧光探针标记人白血病细胞和人脑皮层神经元[Ca2 ]i,激光共聚焦显微镜实时测定不同浓度As2 O3 干预后 [Ca2 ]i的变化并观察蛋白酪氨酸激酶和磷酸酶抑制剂对 [Ca2 ]i变化的影响。磷基转移法测定细胞膜和胞浆的PKC活性。琼脂糖凝胶电泳法观察细胞DNA的片段化。结果　 1μmol /L的As2 O3 使NB4细胞的 [Ca2 ]i明显增高 ,而对人脑皮层神经元 [Ca2 ]i影响不明显。 2 μmol /L以上的As2 O3 引起两种细胞 [Ca2 ]i增高 ,此作用被磷酸酶抑制剂钒酸盐呈浓度依赖性促进 ,被蛋白酪氨酸激酶抑制剂金雀异黄素呈浓度依赖性抑制 ,2 ,5 ,10μmol/L钒酸盐作用 2 4 0s时NB4细胞的 [Ca2 ]i总增加率分别为 (6 .5± 2 .3) % ,(2 1.7± 2 .1) %和 (4 9.2± 2 .5 ) % ;人脑皮层神经元为 (6 .7± 2 .1) % ,(19.4± 2 .5 ) %和 (5 2 .3± 2 .7) % ;2 ,5 ,10 μmol/L金雀异黄素作用 2 4 0s时NB4细胞的总抑制率分别为 (6 .7± 2 .9) % ,(2 5 .6± 2 .5 ) %和 (5 2 .2± 3.5 ) % ;人脑皮层     

Elevated plasma glutathione peroxidase concentration in acute severe asthma: comparison with plasma glutathione peroxidase activity, selenium and malondialdehyde

OBJECTIVE: To investigate plasma glutathione peroxidase concentration, glutathione peroxidase activity, plasma selenium and oxidative stress in acute severe asthma. MATERIAL AND METHODS: The study was case-control in design, with cases presenting to the emergency department with acute severe asthma and controls randomly selected from a larger cross-sectional study. Plasma malondialdehyde (MDA) was used as a measure of oxidative stress and plasma selenium was measured using ICP-MS. Glutathione peroxidase (GPx) activity was analysed using a colorimetric GPx assay and plasma GPx level was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Fifteen cases [mean (range) predicted peak expiratory flow rate (PEFR) of 43% (20-69)] and 15 matched controls were recruited. MDA levels (mean+/-SD) were higher in acute asthma subjects (1.30+/-0.56 micromol/L) than in controls (0.86+/-0.53 micromol/L; p<0.05). There were no differences between cases and controls for selenium (99+/-34 microg/L versus 109+/-17 microg/L) or for GPx activity (39+/-25 nmol min(-1) mL(-1) versus 38+/-24 nmol min(-1) mL(-1)), however, GPx plasma levels measured by ELISA were higher in cases than controls (22.5+/-10.8 mg/L versus 13.8+/-7.3 mg/L; p<0.05). CONCLUSIONS: Patients with acute severe asthma demonstrated increased MDA levels but no differences in plasma selenium levels or GPx activity. GPx levels measured by ELISA were elevated in severe asthma. These results are consistent with an adaptive up-regulation of GPx to protect against oxidative stress.     

Intracellular free calcium concentration and thromboxane A2 formation of vascular smooth muscle cells are influenced by fish oil and n-3 eicosapentaenoic acid.

The effect of fish oil and n-3 eicosapentaenoic acid (EPA) on intracellular free calcium concentration ([Ca2+]i) and thromboxane B2 (TXB2) formation in resting and stimulated cultured rat vascular smooth muscle cells (VSMC) was examined. In resting control cells [Ca2+]i was 147 +/- 15 nmol l-1 (mean +/- SEM, n = 4). After pretreatment of the cells with fish oil or EPA for 24 days the resting [Ca2+]i was decreased to 126 +/- 10 nmol l-1 and 84 +/- 8 nmol-1, respectively. After stimulation of untreated control cells with either 100 nmol l-1 angiotensin II (AII), 40 micrograms ml-1 low-density lipoprotein (LDL), or 100 ng ml-1 of recombinant platelet-derived growth factor (PDGFAB), [Ca2+]i was (in nmol l-1) 306 +/- 31, 217 +/- 25 and 213 +/- 16. Treatment of cells with fish oil or EPA reduced the stimulatory effect of the agonists, and the following [Ca2+]i values (in nmol l-1) were found: 199 +/- 21, 131 +/- 10, 148 +/- 13; and 175 +/- 11, 98 +/- 12, and 103 +/- 6, respectively. PDGFAB induced a four fold increase in TXB2-generation (270 +/- 28 pg mg-1 cell protein compared with 61 +/- 8.2 pg mg-1 in unstimulated control cells) within 6 min. In cells pretreated with fish oil or EPA, TXB2-formation was reduced by 54% and 44%, respectively. In conclusion: in rat VSMC stimulated by a variety of vasoactive agonist, fish oil and EPA can markedly attenuate intracellular mechanisms related to changes of cytosolic calcium concentration and eicosanoid production.(ABSTRACT TRUNCATED AT 250 WORDS)     

Enalapril and losartan affect lipid peroxidation in renal transplant recipients with renin-angiotensin system polymorphisms

OBJECTIVES: In this study, the effect of enalapril (E) and/or losartan (L) on lipid peroxidation (LPO) is studied in renal transplant recipients (RTRs) with regard to polymorphisms of renin-angiotensin system (RAS). DESIGN AND METHODS: After determination of genotypes of the angiotensin-converting enzyme (ACE I/D), angiotensinogen (AGT M235T) and angiotensin II type 1 receptor (ATR1 A1166C) by PCR, sixty-four RTRs recruited to four groups randomly: first (13 patients) and second (20 patients) groups were treated with enalapril (E(+): 10 mg/day) and losartan (L(+): 50 mg/day) alone for 2 months, respectively. After 2 weeks as washout period, E group changed to L and vice versa as a cross-over design and they were treated for another 2 months. The third group (13 patients) as positive control received enalapril+losartan (E(+)L(+): 10 mg/day+50 mg/day) for 16 weeks, and the forth group (18 patients) as negative control received no medication (E(-)L(-)). Malondialdehyde (MDA) as LPO marker was measured before and after treatment. In this study, P<0.05 was considered significant. RESULTS: After 2 months of treatment, MDA level significantly decreased in all of the groups except the E(-)L(-). MDA level in pre- vs. post-intervention for the E(+)L(+), E(+), L(+) and E(-)L(-) groups were as follows: 5.81+/-2.13 nmol/mL vs. 1.61+/-0.80 nmol/mL (P=0.001), 5.10+/-2.05 nmol/mL vs. 1.68+/-1.01 nmol/mL (P=0.003), 5.20+/-1.61 nmol/mL vs. 1.22+/-0.27 nmol/mL (P=0.000) and 5.27+/-2.12 nmol/mL vs. 5.07+/-2.03 nmol/mL (P=0.52), respectively. Also, the same results were found in the end of 16th week. Although patients with DD genotype of ACE had higher MDA (P=0.01) levels, RAS polymorphisms could not predict the antioxidative response rate to the drugs (P>0.05). CONCLUSIONS: E and/or L reduce MDA regardless of the RAS genotypes.     

常规剂量三氧化二砷对心脏功能影响的临床和实验研究

目的　研究常规剂量的三氧化二砷 (As2 O3)对急性早幼粒细胞白血病 (APL)患者心脏功能的影响。方法　通过对患者基础心率和心电图的动态观察 ,膜片钳技术对豚鼠心肌细胞用药前后动作电位和电流的监测 ,激光共聚焦技术对用药前后豚鼠心肌细胞内钙的测定 ,分析As2 O3对APL患者心脏功能影响的可能机制。结果　常规剂量的As2 O3静脉给药第 1～ 2周 ,5 2 .5 %～ 35 .0 %的APL患者产生不同程度的心脏不良反应 ,心电图上QT间期延长等。膜片钳监测显示 1,2 ,5 μmol LAs2 O3使豚鼠心肌细胞动作电位时程从 (5 6 3.0± 5 5 .8)ms分别延长到 (737.7± 131.7)ms、(84 2 .4± 115 .6 )ms和 (110 3.2± 96 .3)ms (P值分别 <0 .0 5 ,0 .0 1,0 .0 1) ,使L 型钙电流增加。激光共聚焦检测结果显示 ,1,2 ,5 μmol LAs2 O3使心肌细胞内钙增加 ,并可以被钙通道阻滞剂阻断。结论　常规剂量的As2 O3可使部分APL患者出现一过性心动过速、QT间期延长等不良反应。As2 O3对心脏功能的影响可能是通过影响心肌离子通道和细胞内钙来实现的。     

A cross-sectional study of basal platelet intracellular free calcium concentration in normotensive and hypertensive primigravid pregnancies

1. The intracellular free calcium concentration ([Ca2+]i) in washed human platelets was measured using the fluorescent indicator, fura-2, in a cross-sectional study of 36 normotensive, primigravid volunteers, 12 in each trimester of pregnancy and a further 12 at 6 weeks post partum. The results were compared with those obtained from 30 normal female volunteers not using oral contraception. 2. The mean basal [Ca2+]i in the platelets of the pregnant women in the first two trimesters (115.6 +/- 6.7 and 120.1 +/- 5.7 nmol/l, respectively) was not shown to differ significantly from that of normal non-pregnant volunteers (112.3 +/- 2.9 nmol/l). However, during the third trimester a significant increase in [Ca2+]i was noted (134.0 +/- 4.9 nmol/l; P less than 0.05), with a return to normal values in the post-partum period (108.2 +/- 6.1 nmol/l). 3. [Ca2+]i was also measured in the platelets of a group of 12 primigravid pregnant women in the third trimester whose pregnancies were complicated by gestational hypertension (pregnancy-induced hypertension and pre-eclampsia). A significant rise in basal [Ca2+]i was noted in the platelets of primigravidae whose pregnancies were complicated by pre-eclampsia (163.6 +/- 8.8 nmol/l) as compared with normotensive, third-trimester primigravidae (P less than 0.02). However, no correlation could be demonstrated between [Ca2+]i and systemic blood pressure.     

粉防己碱对脂多糖致大鼠胰腺腺泡细胞损伤的保护作用及其机制研究

目的探讨粉防己碱（Tet）对脂多糖（LPS）诱发大鼠胰腺腺泡细胞损伤的保护作用及其机制。方法胶原酶法分离雄性SD大鼠胰腺腺泡细胞，预先经Tet（50μmol／L、100μmol／L）处理15min后，再经LPS（10mg／L）或正常培养液处理，在0、1、4和10h采集上清液，检测其中丙二醛（MDA）古量及超氧化物歧化酶（SOD）、磷脂酶A2（PLA2）活性；采用四甲基偶氮唑蓝比色法（MTT）检测胰腺腺泡细胞存活情况；部分胰腺腺泡细胞经Fluo-3／AM荧光探针负载后，于相应时间点采用灌流方式给予Tet或LPS，激光共聚焦显微镜观察单个胰腺腺泡细胞内钙离子浓度（[Ca^2＋]i）。结果Tet可减轻LPS所致的细胞损伤（P均〈0.05），抑制LPS诱发的胰腺腺泡细胞[Ca^2＋]i升高（P均〈0．05），降低细胞培养上清液中MDA含量和PLA2活性、增加SOD活性。结论Tet可能通过抑制钙超载、增强抗氧化能力以及减少胰酶活化，减少LPS所致胰腺腺泡细胞损伤，从而发挥对胰腺腺泡细胞的保护作用。