叉头状转录因子O1对游离脂肪酸诱导的人肝癌细胞株HepG-2胰岛素抵抗和脂质堆积作用的研究

目的研究叉头状转录因子O1（FoxO1）对游离脂肪酸介导的人肝癌细胞株（HepG-2）胰岛素抵抗和脂质堆积的作用以及对固醇调节元件结合蛋白-1c（SREBP-1c）mRNA和蛋白表达的影响。方法将HepG-2细胞培养后用普通培养基培养为对照组,用含5．0×10μmol／L软脂酸的培养基诱导为软脂酸组,诱导后转染空白质粒为空白质粒组,诱导后转染FoxO1siRNA质粒载体为FoxO1siRNA载体组。运用实时定量聚合酶链反应（RT—PCR）方法检测FoxO1mRNA表达,噻唑蓝（M33＂）比色法检测细胞增殖,葡萄糖氧化酶法检测培养基中葡萄糖消耗量,油红O染色观察细胞脂质堆积;RT—PCR和Westernblot技术分别检测SREBP-1c mRNA表达量以及蛋白的表达量。各组间均值比较采用单因素方差分析,样本间比较采用t检验。结果软脂酸组较对照组细胞葡萄糖消耗量减少（1．174-0．56vsVS4．31±0．21,t=10．587,P〈0．01）、细胞中的脂质堆积增多、FoxO1mRNA升高（0．784-0．10vs0．51±0．12,t=3．629,P〈0．05）、SREBP-1cmRNA升高（0．71±0．17vs0．25±0．08,t=6．290,P〈0．05）、SREBP-1c蛋白升高（0．694-0．10vs0．41±0．07,t=4．797,P〈0．01）。转染FoxO1siRNA质粒载体后葡萄糖消耗量较软脂酸组增加（2．26±0．41vs1．17±0．56,t=3．144,P〈0．05）,FoxO1mRNA、SREBP-1cmRNA、SREBP-1c蛋白的表达较软脂酸组均减少且接近于对照组（分别为0．38±0．06vs0．784-0．10,t=7．164,P〈0．01;0．45±0．13vs0．71±0．17,t=2．479,P〈0．05;0．41±0．06vs0．694-0．10,t=4．797,P〈0．01）,细胞中的脂质堆积也较软脂酸组减少。结论抑制FoxO1的表达,可改善游离脂肪酸诱导的细胞胰岛素抵抗、减少肝脏细胞内脂肪变性,其机制可能是通过下调SREBP-1c的表达。     

沉默调节蛋白1抗胰岛INS-1细胞凋亡作用的研究

目的通过观察游离脂肪酸（FFA）对INS-1细胞沉默调节蛋白1（SIRT1）、活性氧（ROS）水平和凋亡的影响,探讨FFA损害胰岛B细胞功能及SIRT1保护细胞的机制。方法将INS-1细胞分为牛血清白蛋白（BSA）对照组和FFA组,作用36h后分别检测SIRT1mRNA水平、ROS水平和凋亡变化。构建SIRT1过表达质粒,转染INS-1细胞,再在上述两组条件下作用36h后分别检测ROS水平和凋亡变化。结果与BSA组比较,FFA组SIRT1mRNA相对表达量下降（0．50±0．127251．02±0．08,P〈0．01）、ROS水平明显增加（458．15±134．94725132．86士51．80,P〈0．01）、凋亡增加（36．55±8．16vs5．85±1．65,P〈0．01）。在FFA作用下,SIRTl过表达质粒转染INS-1细胞后较转染前ROS水平下降（284．80±87．97vs458．15±134．94,P〈0．01）,凋亡减少（18．72±7．13vs36．55±8．16,P〈0．01）。结论FFA对INS-1细胞功能的损害与氧化应激有关,而SIRT1过表达可减少ROS产生,减少凋亡,从而保护INS-1细胞功能。     

姜黄素抑制棕榈酸诱导的巨噬细胞炎症反应的机制研究

目的探讨姜黄素抑制棕榈酸诱导的巨噬细胞炎症反应的作用机制。方法以0、250、500μmol／L棕榈酸干预小鼠巨噬细胞RAW264．724h,观察细胞形态,逆转录一聚合酶链反应（RT-PCR）检测细胞中受体相互作用蛋白140（RIPl40）、肿瘤坏死因子a（TNF-a）、白细胞介素-6（IL-6）mRNA水平,酶联免疫吸附实验（ELISA）检测上清中TNF-a、IL-6水平;噻唑蓝法（MTr）确定姜黄素作用RAW264．7细胞的最佳时间和浓度;细胞分为姜黄素组和对照组,分别给予20μmol／L姜黄素和二甲基亚砜（DMSO）预处理1h后,均给予500μmol／L棕榈酸作用24h,观察细胞形态并检测细胞中RIPl40、TNF-a、IL-6mRNA水平和上清中TNF-a、IL-6浓度。采用单因素方差分析和t检验对研究数据进行统计检验。结果500μmol／L棕榈酸组RIPl40mRNA表达较0μmol／L组显著升高（3．40±0．51比1．01±0．21,t=7．436,P〈0．01）;0、250、500μmol／L棕榈酸组TNF-amRNA（1．00±0．03、1．79±0．12、2．16±0．13）和蛋白[（197±25）、（371±10）、（485±17）ng／L]、IL-6mRNA（1．00±0．51、2．55±0．15、2．59±0．17）和蛋白[（953±66）、（1081±36）、（1182±18）ng／L]与棕榈酸剂量明显相关（F=99．308、187．049、152．958、26．594,均P〈0．01）;棕榈酸处理后,细胞变圆、皱缩甚至崩解;姜黄素作用RAW264．7细胞的最佳时间为1h,最佳浓度为20ixmol／L;姜黄素组与对照组相比,RIPl40mRNA（1．00±0．05比0．63±0．01,t=一13．79,P〈0．01）、TNF-amRNA（0．64±0．11比1．00±0．07,t=一4．532,P〈0．05）和蛋白[（322±12）比（485±17）ng／L,t=一13．577,P〈0．01]、IL-6mRNA（0．57±0．05比1．00±0．02,t=一14．167,P〈0．01）和蛋白[（241±47）比（1182±18）ng／L,t=一44．810,P〈0．01]均显著降低,而细胞形态正常,细胞问仍有连接融合。结论RIPl40可能参与姜黄素抑制棕榈酸诱导的炎症反应过程。     

氧化低密度脂蛋白、荷叶生物碱对THP-1巨噬细胞源性泡沫细胞ABCA1表达的影响

目的：了解不同浓度氧化低密度脂蛋白（ox-LDL）及荷叶生物碱对THP-1巨噬细胞源性泡沫细胞三磷酸腺苷结合盒转运蛋白A1（ABCA1）表达的影响。方法：用佛波酯（PMA）诱导THP-1源性单核细胞分化为巨噬细胞：以不同浓度的ox-LDL孵育其24h;50mg/L的ox-LDL孵育使该细胞成为泡沫细胞,再以不同浓度荷叶生物碱对其进行干预24h。以PCR和蛋白质免疫印迹法（Western blot）分别检测不同浓度ox-LDL及荷叶生物碱干预下各组细胞ABCA1的表达。以油红O染色观察各组细胞。结果：镜下：ox-LDL处理组细胞内脂滴的大小与多少随着ox-LDL的浓度的增加而增加;随荷叶生物碱浓度的升高而减少。ABCA1mRNA表达量：ox-LDL各组的表达量均较空白对照组明显升高[25mg/L组：（1.4677±0.0907）,50mg/L组：（2.0510±0.1065）,100 mg/L组：（1.5356±0.0903）比0mg/L组：（1.00）,P均〈0.05],荷叶生物碱各组细胞的表达量[荷叶生物碱25mg/L：（1.0460±0.0580）,50mg/L：（0.8391±0.0661）,100mg/L：（1.1003±0.0752）]表达量均较单纯50mg/L ox-LDL干预组（0.5136±0.0632）明显升高（P均〈0.05）。ABCA1蛋白的表达与ABCA1mRNA表达水平改变相一致。结论：ox-LDL可上调PMA诱导的THP-1单核细胞源性巨噬细胞内ABCA1的表达,使其细胞内脂质蓄积。荷叶生物碱既使上述细胞内ABCA1表达上调,又使其细胞内脂质蓄积减少。     

支气管哮喘小鼠模型中维生素D相关分子的表达

目的探讨维生素D相关分子在支气管哮喘（简称哮喘）小鼠模型中的表达及地塞米松的干预效果。方法用卵白蛋白作为致敏原制备小鼠哮喘模型,随机分为两组（n=6）,分别为地塞米松处理组和生理盐水处理组（对照组）,收集各组小鼠的支气管肺泡灌洗液和支气管组织,计数总细胞数和白细胞分类数,采用real—time RT-PCR技术检测支气管组织中维生素D3上调蛋白1（VDUP1）、维生素D受体（VDR）和1口羟化酶CYP27B1的mRNA表达水平。结果哮喘组支气管组织中VDUP,mRNA、VDRmRNA和CYP27B1mRNA水平分别为（2．74±0．99）、（7．06±4．05）和（3．40±2．16）,明显高于对照组（分别为1．01±0．18、1．28±0．76、1．45±1．39,P〈0．05）和地塞米松治疗组（分别为0．94±0．34、0．76±0．18、0．27±0．17,P〈0．01）。结论维生素D相关分子可能参与了哮喘的发病过程。     

程序性细胞死亡因子4过表达对胃癌细胞BGC823凋亡及凋亡调控蛋白的影响

目的通过稳定转染程序性细胞死亡因子4（programmed cell death4,PDCIM）基因至胃癌细胞BGC823中,观察过表达PDCD4对BGC823凋亡的作用及对凋亡相关调控蛋白Akt／p-Akt、FLIP、caspase-8及cleaved-caspase-8的影响。方法构建针对人PDCD4的真核表达载体并转染至BGC823细胞,Annexin V—FITC／PI联合流式细胞仪检测细胞凋亡,Western Blot检测蛋白的表达。结果成功构建PDCD4真核表达载体并转染至BGC823中,获得稳定过表达PDCD4的细胞模型,过表达PDCD4的BGC823细胞凋亡率（10．82％±1．29％）较未转染组（5．06％±0．83％）明显升高（P〈0．05）。转染PDCD4后,Akt／p-Akt表达（0．25±0．04／0．06±0．01）较未转染组（0．65±0．09／0．18±0．02）明显降低（P〈0．01）,FLIP蛋白在转染组中的表达（0．12±0．01）较未转染组中的表达（0．48±0．06）明显降低（P〈0．01）,而转染组caspase-8（0．36±0．07）及cleaved—caspasc-8（0．24±0．05）较未转染组caspase-8（0．18±0．04）及cleaved-caspase-8（0．11±0．02）明显升高（P〈0．05）。结论PDCD4过表达可促进胃癌细胞BGC823的凋亡,并且抑制Akt和FLIP的表达,从而促进caspase-8的活性。     

IL-1β上调大鼠HSCs TIMP-1 mRNA表达与JNK和P38通路的关系

目的探讨IL-1β调控大鼠HSCsTIMP-1mRNA表达与JNK、p38 MAPK通路的关系。方法RT-PCR用于检测大鼠HSCs TIMP-1 mRNA表达；Western blot用于测定IL-1刺激HSCs后JNK、p38的活化程度。结果IL-1β（10ng／mL）作用培养的HSCs 24h后，TIMP-1 mRNA表达（1．191±0．079）明显高于对照组（0．545±0．091），有统计学意义（P〈0．01）；IL-1β以时间依赖方式激活JNK、p38通路。用不同浓度JNK阻断剂-SP600125预处理HSCs后，IL-1β上调HSCs TIMP-1 mRNA表达作用受到抑制，分别为10μmol／L，1．022±0．113;20μmol／L，0．8694±0．070；40μmol／L，0．666±0．123，与对照组相比（1．163±0．107），各浓度组均有显著性差异（P〈0．05，P〈0．01，P〈0．01）。用不同浓度p38阻断剂-SB203580预处理HSCs后，HSCs表达TIMP-1 mRNA逐渐增多，分别为10μmol／L，1．507±0．099；20μmol／L，1．698±0．107；40μmol／L，1．857±0．054。与对照组相比（1．027±0．061），各浓度组均有显著性差异（P均〈0．01）。结论IL-1β可通过上调HSCs TIMP-1 mRNA的表达来加速肝纤维化的发生发展，JNK和p38信号蛋白参与了此过程，HSCs中两条通路均可被IL-1激活，但所起作用完全不同，它们相互作用相互调节，共同调控TIMP-1 mRNA的表达。     

非酒精性脂肪性肝炎大鼠肝组织Bcl-2和Bax的表达及其意义

目的探讨凋亡调控蛋白Bel-2和Bax表达在大鼠非酒精性脂肪性肝炎发病中的作用。方法将20只Wistar大鼠随机分为普通饲料喂养组（正常组）和高脂饲料喂养组（模型组）,连续喂养12周后,测定血清甘油三酯（TG）、总胆固醇（TC）、丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）,观察肝组织病理学变化和炎症活动度计分,采用westem blot法检测肝组织Bcl-2和Bax的表达。结果模型组大鼠肝小叶内肝细胞呈弥漫性脂肪变,伴大量炎性细胞浸润及散在性点状坏死;模型组动物肝组织Bax蛋白表达较正常组显著性升高（1．02±0．33对0．51±0．03,P〈0．01）,而Bel-2蛋白较正常组则明显下降（0．15±0．31对0．52±0．01,P〈0．01）,Bel-2／Bax比值降低（0．14±0．01对1．03±0．06,P〈0．01）。结论凋亡调控蛋白Bel-2和Bax的表达变化可能参与了NASH的发生和发展过程。     

整合酶相互作用分子1基因对糖尿病下肢缺血性疾病的影响

目的检测整合酶相互作用分子1（INII）基因在糖尿病大鼠下肢缺血性疾病血管中的表达,探讨其对血管内皮细胞影响的分子机制。方法以8周龄的雄性SD大鼠为研究对象,通过尾静脉注射链脲佐菌素（STZ）的方法获得16只糖尿病大鼠模型,以完全随机分组方法将大鼠分为2组（每组8只）：实验组部分结扎双侧股外动脉制作下肢缺血模型,对照组仅进行糖尿病造模,不作其他处理。以实时荧光定量逆转录聚合酶链反应（RT-PCR）和Western blotting技术检测2组下肢动脉壁INII的mRNA和蛋白表达情况。合成针对删门的小干扰RNA（siRNA．INll）,并转染入人脐静脉血管内皮细胞株HUVEC-12,对照组分别为无关序列转染及脂质体对照;应用噻唑蓝（MTT）比色法、Transwell侵袭小室实验、RT—PCR、Western blotting等技术检测转染INII—siRNA前后HUVEC．12细胞迁移及血管生成能力的变化,进一步检测迁移相关基因细胞间黏附分子1（ICAM-1）、基质金属蛋白酶2（MMP-2）、基质金属蛋白酶抑制物1（TIMP-1）和血管生成相关基因血管内皮生长因子（VEGF）、碱性成纤维细胞生长因子（bFGF）、血管紧张素2（Ang-2）的变化情况。以t检验与方差分析做组问数据对比。结果糖尿病下肢缺血大鼠的动脉壁内删7mRNA和蛋白表达均较对照组明显增加（分别为0．83±0．07、0．21±0．03和0．92±0．08、0．31±0．03,t=23．03、20．19,均P〈0．01）;转染后与脂质体及无关序列对照组相比,INII-siRNA组HUVEC-12细胞INII mRNA及蛋白表达均显著降低（INII mRNA分别为0．26±0．01、0．75±0．08、0．80±0．07,INII 蛋白分别为0．11±0．02、0．79±0．12、0．82±0．14,F=36．49、24．17,均P〈0．01）;INII-siRNA组迁移能力明显增强（分别为66±5、35±3、37±5,F=19．39,P〈0．01）。与两对照组相比,MJ-siRNA组HUVEC-12中ICAM-1、MMP-2、VEGF、bFGF和Ang-2的mRNA和蛋白表达明显增强（均P〈0．05）,TIMP-1的mRNA和蛋白表达显著降低（F：36．48、237．91,P〈0．05）。结论 INII 可抑制血管内皮细胞的迁移和血管生成能力,该效应可能是通过调控细胞中ICAM-1、MMP-2、TIMP-1、VEGF、bFGF和Ang-2的表达实现的。     

2型糖尿病患者单核巨噬细胞PPARγ的mRNA表达及人参皂苷对其表达的影响

将研究人群分为对照组、T2DM组,年龄、性别、BMI等基本相配,T2DM组随机分为：DM1组;DM2组。分离人外周血单核巨噬细胞,采用逆转录PCR技术扩增PPARγ基因片段,检测其表达水平,及血清葡萄糖（BG）、甘油三脂（TG）、胆固醇（TC）水平。结果：T2DM患者外周血单核巨噬细胞PPARγ,mRNA表达比对照组明显减少（P〈0．01）,1．41g／d人参皂苷X14d使PPARγ mRNA表达显著增加（P〈0．05）,并能降低血TG及TC（P〈0．05,P〈0．05）水平。结论：T2DM患者单核巨噬细胞PPARγ mRNA表达减少,而人参皂苷能有效提高PPARγ mRNA的表达,同时降低血清TG、TC含量。     

Elevated blood pressure and risk of end-stage renal disease in subjects without baseline kidney disease

BACKGROUND: Many cases of end-stage renal disease (ESRD) are ascribed to hypertension. However, because renal disease itself can raise blood pressure, some investigators argue that ESRD seen in patients with hypertension is due to underlying primary renal disease. Previous cohort studies of the relationship between blood pressure and ESRD did not uniformly screen out baseline kidney disease. METHODS: We conducted a historical cohort study among members of Kaiser Permanente of Northern California, a large integrated health care delivery system. The ESRD cases were ascertained by matching with the US Renal Data System registry. RESULTS: A total of 316 675 adult Kaiser members participated in the Multiphasic Health Checkups from 1964 to 1985. All subjects had estimated glomerular filtration rates of 60 mL /min per 1.73 m(2) or higher and negative dipstick urinalysis results for proteinuria or hematuria. During 8 210 431 person-years of follow-up, 1149 cases of ESRD occurred. Compared with subjects with a blood pressure less than 120/80 mm Hg, the adjusted relative risks for developing ESRD were 1.62 (95% confidence interval [CI], 1.27-2.07) for blood pressures of 120 to 129/80 to 84 mm Hg, 1.98 (95% CI, 1.55-2.52) for blood pressures of 130 to 139/85 to 89 mm Hg, 2.59 (95% CI, 2.07-3.25) for blood pressures of 140 to 159/90 to 99 mm Hg, 3.86 (95% CI, 3.00-4.96) for blood pressures of 160 to 179/100 to 109 mm Hg, 3.88 (95% CI, 2.82-5.34) for blood pressures of 180 to 209/110 to 119 mm Hg, and 4.25 (95% CI, 2.63-6.86) for blood pressures of 210/120 mm Hg or higher. Similar associations between blood pressure level and ESRD risk were seen in all subgroup analyses. CONCLUSIONS: Even relatively modest elevation in blood pressure is an independent risk factor for ESRD. The observed relationship does not appear to be due to confounding by clinically evident baseline kidney disease.     

血压不同控制水平对老年男性高血压患者心血管事件的影响

目的了解老年男性高血压降压过程中有无"J"型曲线现象,探讨老年高血压降压的合适范围。方法选择老年男性高血压患者846例,根据收缩压和舒张压水平分别分为:≤120 mm Hg(1mm Hg=0.133 kPa(S1组)213例,1 21～130 mm Hg(S2组)21 5例,131～140 mm Hg(S3组)219例,1 41～150 mm Hg(S4组)121例,>1 50mm Hg(S5组)78例;≤60 mm Hg(D1组)107例,61～70 mm Hg(D2组)258例,71～80 mm Hg(D3组)339例,81～90 mm Hg(D4组)125例,>90 mm Hg(D5组)17例。分析不同血压水平与心血管事件的关系。结果 S5组心血管死亡、致死脑卒中、非致死心肌梗死(MI)和脑卒中发生率最高,S4组心血管死亡、冠心病死亡、致死脑卒中和非致死MI发生率最低,组间比较差异显著(P<0.05,P<0.01)。D5组全因死亡、心血管死亡、冠心病死亡、致死脑梗死、非致死MI和脑卒中发生率最高,D4组全因死亡、心血管死亡、冠心病死亡发生率最低,组间比较差异显著(P<0.05)。结论老年男性高血压降压过程中可见"J"型曲线,降压合适范围为140～150/80～90 mm Hg。     

Are aneroid sphygmomanometers accurate in hospital and clinic settings?

BACKGROUND: The aneroid sphygmomanometer is commonly used for the indirect measurement of blood pressure despite significant concerns about its accuracy. Although the mercury sphygmomanometer is highly accurate, there are concerns about the environmental toxicity of mercury. In response to various external pressures to become essentially mercury free, the Mayo Clinic, Rochester, Minn, has replaced many mercury sphygmomanometers with aneroid devices. Since 1993, a maintenance protocol has been in place to ensure proper function and accuracy of these devices. METHODS: We assessed the accuracy of 283 aneroid devices using as the reference standard a digital pressure and vacuum meter that was calibrated using a mercury sphygmomanometer. RESULTS: The mean +/- SD values from the aneroid device in millimeters of mercury at each reference point (at 20-mm Hg intervals from 60 to 240 mm Hg defined by the reference device) were 59.9 +/- 1.9 at 60; 79.9 +/- 1.9 at 80; 100.0 +/- 1.8 at 100; 120.3 +/- 1.8 at 120; 140.7 +/- 1.4 at 140; 160.7 +/- 1.7 at 160; 180.9 +/- 1.3 at 180; 200.7 +/- 5.0 at 200; 221.0 +/- 1.3 at 220; and 240.8 +/- 1.6 at 240 (r = 0.99; P<.001). The values from the aneroid device underestimated those of the reference device by a mean of 0.5 mm Hg (95% confidence interval, 0.3-0.7). Virtually 100% of the values from the aneroid device were within the 4-mm Hg range recommended by the Association for the Advancement of Medical Instrumentation. CONCLUSION: Aneroid sphygmomanometers provide accurate pressure measurements when a proper maintenance protocol is followed.     

Assessment on antihypertensive effect and safety of nifedipine controlled-release tablet administered at 80 mg/day in practical clinic

In this study, the effect of nifedipine controlled-release tablets at a dose of 80 mg/day (NCR80) on blood pressure (BP) and safety was investigated. In essential hypertension (n = 50, >140/90 mm Hg) despite a combined therapy with antihypertensive agents, NCR80 was administered instead of the previous antihypertensive agents and changes in BP and pulse rate (PR), side effects, and changes in laboratory test values were examined for 24 months. Thirty-three patients switched to NCR80 as the initial dose from the previous antihypertensive agents (Initial), while 17 patients started treatment at NCR40 and increased to NCR80 after 1-3 months (Up-titration). In the Initial group, BP decreased significantly and this significant reduction continued for 24 months, but not in the case of PR. In the Up-titration group, BP decreased significantly during the treatment with NCR40, and further reduced in 1-2 month(s) after NCR80. This significant reduction continued for 12 months, but not in the case of PR. The mean change in BP after increasing NCR40 to NCR80 was -16/-6 mm Hg at 6 months. When patients who received NCR80 were stratified into three grades according to the baseline systolic blood pressure level (SBP) (≥180, 160-179, and 140-159 mm Hg), the mean change in BP at 1 month was -55, -27, and -16 mm Hg, respectively. None of the 50 patients treated with NCR80 experienced any side effects and no abnormal change was observed in their laboratory test values. These findings suggested that NCR80 demonstrated the ability to control BP appropriately depending on the severity with favorable safety.     

Effects of blood pressure level on progression of diabetic nephropathy: results from the RENAAL study

BACKGROUND: Clinical trials of nephropathy in people with type 2 diabetes mellitus have not examined the effects of systolic blood pressure (SBP) or pulse pressure (PP) on the time to end-stage renal disease (ESRD) or death. OBJECTIVES: To evaluate the impact of baseline and treated SBP, diastolic blood pressure (DBP), and PP on composite and individual outcomes including doubling of serum creatinine, ESRD, or death in participants of the Reduction of Endpoints in NIDDM (non-insulin-dependent diabetes mellitus) With the Angiotensin II Antagonist Losartan (RENAAL) Study; to assess the specific effect of the angiotensin receptor blocker losartan potassium on composite and renal outcomes; and to explore the implications of dihydropyridine calcium channel blockers as concurrent therapy on composite and renal outcomes. DESIGN: A Cox proportional hazards regression model was used to assess the hazard risk profile of baseline SBP (categories: <130, 130-139, 140-159, 160-179, and > or =180 mm Hg), DBP (categories: <70, 70-79, 80-89, 90-99, and > or =100 mm Hg), and PP (categories: <60, 60-69, 70-79, 80-89, and > or =90 mm Hg) on renal outcomes. PARTICIPANTS: The study comprised 1513 participants with established nephropathy and hypertension associated with type 2 diabetes. INTERVENTIONS: The RENAAL study was a randomized, placebo-controlled study of losartan vs placebo, with other agents added to achieve the goal of a trough BP (ie, BP immediately prior to the next dosing) below 140/90 mm Hg, and had a mean follow-up of 3.4 years. MAIN OUTCOME MEASURES: The primary analysis was time to composite end point of doubling of serum creatinine, ESRD, or death. RESULTS: A baseline SBP range of 140 to 159 mm Hg increased risk for ESRD or death by 38% (P =.05) compared with those below 130 mm Hg. In a multivariate model, every 10-mm Hg rise in baseline SBP increased the risk for ESRD or death by 6.7% (P =.007); the same rise in DBP decreased the risk by 10.9% (P =.01) when adjusting for urinary albumin-creatinine ratio, serum creatinine, serum albumin, hemoglobin, and hemoglobin A1c. Those randomized to the losartan group with a baseline PP above 90 mm Hg had a 53.5% risk reduction for ESRD alone (P =.003) and a 35.5% risk reduction for ESRD or death (P =.02) compared with the placebo group. CONCLUSIONS: Baseline SBP is a stronger predictor than DBP of renal outcomes in those with nephropathy resulting from type 2 diabetes. Those with the highest baseline PP have the highest risk for nephropathy progression but also garner the greatest risk reduction with SBP lowered to less than 140 mm Hg.     

Efficacy and Safety of Irbesartan/HCTZ in Severe Hypertension According to Cardiometabolic Factors

J Clin Hypertens (Greenwich).2010;12:487–494. © 2010 Wiley Periodicals, Inc. This post hoc analysis of a 7-week, randomized, double-blind trial evaluated the efficacy and safety of initial irbesartan/hydrochlorothiazide treatment in 468 patients with severe, uncontrolled, hypertension (diastolic blood pressure [DBP] ≥100 mm Hg) at high cardiovascular risk. Systolic blood pressure (SBP)/DBP reductions ranged from 28.0 to 42.9/22.9 to 27.2 mm Hg in patients with obesity, diabetes, baseline SBP ≥180 mm Hg, and in the elderly. Blood pressure control to <140/90 mm Hg in the age and obesity subgroups ranged from 32.1% to 39.2% while control to <130/80 mm Hg in patients with diabetes was 11.5%. After 1 week of therapy, 72.5% of patients no longer had SBP ≥180 mm Hg; by 7 weeks, 51.3% had SBP 140 to 159 mm Hg and 26.5% had SBP <140 mm Hg. Treatment was well tolerated regardless of the subgroup. No excess of prespecified events was noted. Thus, initial treatment with irbesartan/hydrochlorothiazide was rapidly effective in high-risk, difficult-to-treat, severely hypertensive patients.     

Pressure-dependent contraction of rat juxtamedullary afferent arterioles

Pressure-diameter relations were studied in rat afferent arterioles using an isolated, juxtamedullary nephron preparation perfused with a saline solution containing 5% albumin. Angiotensin I (10 microM), angiotensin II (0.1 microM), and norepinephrine (10 microM) increased perfusion pressure, and norepinephrine, but not angiotensin I or II, contracted afferent arterioles, indicating that the vessels are reactive. The control diameter of the afferent arterioles that exhibited pressure-dependent contraction (n = 58) averaged 30.8 +/- 1.1 micron at perfusion pressure of 80 mm Hg. When pressure was increased from 80 to 120 and then to 180 mm Hg, the diameter of these arterioles decreased by 16.4 +/- 2.1%. Glomerular capillary pressure was well autoregulated and averaged 45.2 +/- 2.2, 50.2 +/- 2.4, and 53.0 +/- 3.0 mm Hg, respectively, at perfusion pressures of 80, 120, and 180 mm Hg. Administration of vasodilators or a Ca2+-free solution eliminated the contractile response to pressure elevations; rather, the diameter of these vessels increased significantly by 17.5 +/- 5.1% and 32.0 +/- 9.4%, respectively, when pressure was increased from 80 to 180 mm Hg. Blocking tubuloglomerular feedback mechanism, with furosemide or by removal of the renal papilla (which interrupts the delivery of fluid to the macula densa), eliminated the pressure-dependent contraction of the afferent arterioles. Instead the diameter of these vessels increased by 27.0 +/- 7.8% and 36.0 +/- 5.6%, respectively, when the pressure was increased from 80 to 120 and then to 180 mm Hg. These results demonstrate that juxtamedullary nephrons perfused in vitro autoregulate glomerular capillary pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Predictors of uncontrolled hypertension in ambulatory patients

Hypertension remains poorly controlled in the United States. Improvement of its management will require an understanding of the patient characteristics and treatment factors associated with uncontrolled hypertension. We studied antihypertensive medication use, comorbidity, and blood pressure measurements for 525 hypertensive patients in 3 different healthcare systems over a 1-year period. We concomitantly conducted comprehensive patient interviews covering demographic factors, knowledge of hypertension and its treatment, and medication side effects. Ordinal logistic regression was used to identify factors associated with poor blood pressure control. Mean age of the patients was 65+/-11 years. Mean systolic blood pressure (SBP) was 143+/-15 mm Hg; and mean diastolic blood pressure (DBP), 80+/-9 mm Hg. Only 39% (203/525) of patients had mean blood pressure <140/90 mm Hg during the study period; about half (257/525) had stage 1 hypertension (mean SBP 140 to 159 mm Hg and/or mean DBP 90 to 99 mm Hg), and 12% (65/525) had stage 2 or greater hypertension (SBP >160 mm Hgand/or DBP >100 mm Hg). Multivariate analysis revealed several independent predictors of poor control: older age, multi-drug regimens, lack of knowledge by the patient of their target SBP, and a report of antihypertensive drug side effects. Patients with angina had a higher likelihood of adequate blood pressure control. Fewer than 40% of the treated patients studied had a mean blood pressure 相似文献   

罗格列酮在老年2型糖尿病患者中的降压与内皮保护作用

目的 观察胰岛素增敏剂罗格列酮对老年2型糖尿病患者的降压作用及其对血管内皮的保护作用.方法 将104例无高血压史(未服用降压相关药物)的老年2型糖尿病患者按初诊收缩压(SBP)分为3组,理想血压组(SBP≤120 mm Hg,1 mm Hg=0.133 kPa)42例,例,前期高血压组(140mm Hg≥SBP>120 mm Hg)33例,轻度高血压组(160 mm Hg≥SBP>140 mm Hg)29例.维持原治疗不变,应用岁格列酮4 mg/d,治疗12周.测定治疗前、后SBP、舒张压(DBP)、空腹血糖(FBG)、糖化血红蛋白(Hb)Alc、稳态模型评估一胰岛素抵抗指数(HOMA-IR)、总胆固醇(TC)、低密度脂蛋白(LDL)、vWF、白细胞(WBC)计数、C反应蛋白(CRP)、非对称性二甲基精氨酸(ADMA)水平.结果 用药12周后,轻度高血压组治疗后SBP及DBP均较治疗前有所下降,差异有统计学意义(P<0.05).前期高血压组治疗后SBP 下降,有统计学意义(P<0.05),而DBP虽下降,但无统计学意义.3组FBG、HbAlC、HOMA-IR、TC、LDL较治疗前下降,差异有统计学意义(P<0.05).另外,治疗后vWF、WBC及CRP也较治疗前下降,筹异有统计学意义(P<0.05).结论 罗格列酮可以降低老年2型糖尿病患者的SBP及DBP,对于基础血压高者降压效果更为显著,同时还可改善内皮细胞功能,发挥保护内皮的作用.     

老年卒中患者急性期血压变化及其与短期预后的关系

目的 探讨老年卒中患者急性期血压变化特征及其与30 d预后的关系.方法 采用前瞻性队列研究方法,连续登记2008年1月-2010年6月入院的老年卒中患者275例,其中脑梗死202例,脑出血73例.连续记录入院后7d的血压,在发病30d时评价预后.按照急性期7d内平均收缩压（120～139、140～159、160～179、180～199、＞200 mm Hg）和舒张压（＜69、70～79、80～89、90～99、＞100 mm Hg）水平分别分为5个亚组,比较入院时和30 d时的改良Rankin量表评分（mRS）、美国国立卫生研究院卒中量表评分（NIHSS）.结果 ①275例患者中,有66例预后差,其中脑出血组22例,脑梗死组44例,两组比较差异无统计学意义（P=0.200）.两组急性期7d内不同平均收缩压的30d预后差者的5个亚组预后比较,筹异有统计学意义（P＜0.05）.而急性期7 d内,不同平均舒张压水平的30 d预后差者,5个亚组比较,除70～79 mm Hg与80～89 mm Hg两组间差异无统计学意义外（P＞0.05）,其余各亚组之间预后比较差异有统计学意义（P＜0.05）.②平均收缩血压在160～179mmHg者,mRS（中位数2）和NIHSS（中位数7）评分较低,相应30d改善显著（mRS中位数差值为2,NIHSS中位数差值为4）;平均舒张压＞100 mm Hg,提示预后差,mRS和NIHSS评分30d改善的比较,不同舒张压亚组两两比较,差异有统计学意义（P＜0.05）.脑出血组平均舒张压在70～90mmHg范围内,往往预后较好;腩梗死组在70mm Hg以下者,预后最好.结论 老年卒中患者急性期7 d内平均收缩压在160～179mm Hg之间,30 d的预后较好;急性期平均舒张血压不能预测病情的严重程度,但可反映30 d预后转归的倾向.