沙库巴曲缬沙坦治疗慢性心衰对患者心肾功能指标的影响

目的：观察沙库巴曲缬沙坦治疗慢性心力衰竭的临床疗效及对患者肾功能、心功能及血清指标的影响。方法：选取2018年1月~2019年1月收治的102例慢性心力衰竭患者,随机分为培哚普利组和诺欣妥组,各51例。两组均给予基础治疗,在此基础上培哚普利组给予培哚普利治疗,诺欣妥组给予沙库巴曲缬沙坦治疗。评估两组临床疗效,心功能、肾功能、血清标志物水平的变化情况,统计两组不良反应发生情况、心血管不良事件发生情况。结果：诺欣妥组总有效率优于培哚普利组（P＜0.05）;诺欣妥组心功能标志物水平低于培哚普利组,左室射血分数高于培哚普利组,肾功能指标优于培哚普利组（P＜0.05）;诺欣妥组不良反应、心血管不良事件发生率低于培哚普利组（P＜0.05）。结论：沙库巴曲缬沙坦联合基础治疗对慢性心衰疗效理想,能够改善患者肾功能,用药安全性高。     

培哚普利联合厄贝沙坦对扩张型心肌病大鼠心功能及心肌NF-kB活性的影响

[目的]观察培哚普利联合厄贝沙坦对扩张型心肌病(DCM)大鼠的心功能及心肌核因子-kB(NF-κB)活性的影响.[方法]通过腹腔注射阿霉素建立大鼠DCM模型.13周后,大鼠分为4组:A组为正常大鼠;B、C、D组均为DCM大鼠.A、B组不予药物干预,C组予以培哚普利,D组予以培哚普利联合厄贝沙坦.超声心动图测定左室射血分数(LVEF),ELISA方法检测血浆脑利钠肽(BNP)水平,免疫组化方法检测心肌NF-κB的活化.[结果]药物治疗3周后,与C组比较:①D组LVEF更明显升高(P＜0.01);②D组BNP水平更明显下降(P＜0.01);③D组NF-κB活性更明显减弱(P＜0.01);④BNP水平、NF-κB活性均与LVEF呈负相关(r=-0.85,P＜0.01;r=-0.80,P＜0.01),NF-κB活性与BNP水平呈正相关(r=0.90,P＜0.01).[结论]心肌NF-κB的过度活化,损害了心功能.培哚普利联合厄贝沙坦治疗DCM大鼠,较单用培哚普利更明显改善心功能,机制可能为更明显降低心肌NF-κB活性.     

培哚普利对慢性心力衰竭患者血清纤维化指标的影响

目的　探讨培哚普利对不同程度心力衰竭患者 (CHF)血清中心肌纤维化指标透明质酸酶(HA)、Ⅲ型前胶原氨基端肽 (PⅢP)、层粘连蛋白 (LN)变化的影响。方法　采用放射免疫法检测 5 0例CHF患者给予培哚普利治疗前后血清HA、PⅢP、LN水平的变化及其差异。结果　心功能Ⅲ、Ⅳ级患者血清HA、LN、PⅢP水平显著高于心功能Ⅱ级的患者 (P <0 .0 5 ) ,经培哚普利治疗后 ,血清HA、LN、PⅢP水平显著下降 (P <0 .0 5 ) ,心功能明显改善。结论　血清HA、LN、PⅢP参与了CHF的心肌纤维化 ,且心肌纤维化随CHF的严重程度而加重 ,培哚普利可减缓心肌纤维化的进程 ,并且保护和改善CHF患者的心功能。     

培哚普利对原发性高血压患者血清肿瘤坏死因子-α和白细胞介素-6水平的影响

目的:观察培哚普利对原发性高血压患者血清肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)水平的影响.方法:80例原发性高血压患者随机分为对照组和治疗组,每组40例,对照组服用尼群地平片,治疗组服用培哚普利,治疗8周,分别于治疗前后检测患者血清中细胞因子TNF-α和IL-6水平.结果:治疗组和对照组在治疗前比较,血清TNF-α、IL-6 水平之间比较差异无统计学意义(P ＞ 0.05).治疗后,治疗组TNF-α和IL-6水平均下降(均P ＜ 0.01),而对照组下降不明显,治疗组与对照组比较TNF-α和IL-6 水平差异有统计学意义(P ＜ 0.05).结论:培哚普利能降低原发性高血压患者的血压,同时培哚普利能通过调节炎性细胞因子的产生,抑制炎症反应,从而有益于血压的控制.     

慢性充血性心力衰竭患者血清TNF-α和IL-6的变化及芪苈强心胶囊对其水平的影响

[目的]探讨充血性心力衰竭(CHF)患者血清肿瘤坏死因子-α(TNF-α)和白介素-6(IL-6)的变化及芪苈强心胶囊对其水平的影响.[方法]采用放射免疫分析法,测定50例CHF患者和30例健康对照者血清TNF-α和IL-6水平;将CHF患者随机分为芪苈强心胶囊组和常规治疗组,治疗4周,重复上述检测.[结果]CHF组患者血清TNF-α和IL-6水平明显高于对照组(P＜0.01),且与心功能损害程度密切相关;经4周治疗后芪苈强心胶囊组与常规治疗组比较血清TNF-α和IL-6水平明显降低(P＜0.01),而LVEF则升高更明显(P＜0.05).[结论]CHF患者血清TNF-α和IL-6水平明显增高且与心功能状态密切相关;芪苈强心胶囊具有改善CHF患者心功能和降低血清TNF-α和IL-6水平的作用.     

咪达普利与培哚普利降压疗效和不良反应的对照研究

目的：比较咪达普利与培哚普利对原发性高血压患者的的降压效果和不良反应。方法：将入选的60例1～2级高血压病患者,随机分为2组,咪达普利组,每日晨起口服咪达普利（5～10mg,1次/d）,培哚普利组,每日晨起口服培哚普利（4～8mg,1次/d）。治疗4周,观察2组治疗前、后的血压,记录不良反应。结果：经治疗后咪达普利与培哚普利组血压均明显下降（P〈0.05）,组间差异无统计学意义（P〉0.05）;总不良反应发生率咪达普利组16.8%,培哚普利组20%,而咪达普利组的咳嗽发生率为6.8%,培哚普利组为16.8%。结论：咪达普利和培哚普利均能有效降压,二者降压效果相似,但咪达普利的咳嗽发生率较低。     

洛沙坦和培哚普利对急性心肌梗死后左心室重塑的疗效比较

目的：观察洛沙坦和培哚普利对急性心肌梗死（AMI）患者，左心室重塑（LVRM）的治疗效应并进行比较。方法：AMI患者65例，随机分为3组。洛沙坦组22例，培哚普利组22例，对照组21例。对照组仅给予硝酸酯类、肠溶阿司匹林、肝素等常规治疗；洛沙坦组在常规治疗基础上加用洛沙坦25mg口服，每日1次；培哚普利组在常规治疗基础上加用培哚普利4mg口服，每日1次。分别在入院后第1天、14天、6个月时采用超声心动图，测定左心室舒张末期内径（LVDd）、左心室收缩末期内径（LVDs）、左心室射血分数（LVEF）并进行比较。结果：对照组14天及6个月时LVDd、LVDs较基础值增加，有显著性差异（P＜0．05）；洛沙坦组与培哚普利组14天及6个月时LVDd、LVDs与基础值比较轻度增加，与对照组比较明显缩小，有显著性差异（P＜0．05）；洛沙坦组与培哚普利组LVDd、LVDs变化无显著性差异（P＞0．05）。培哚普利组咳嗽发生率18％，洛沙坦组无1例发生副反应。结论：洛沙坦与培哚普利具有相似的抗左心室重塑的治疗效应，洛沙坦耐受性更好。     

培哚普利与卡托普利治疗充血性心衰的疗效观察

目的:观察比较培哚普利与卡托普利治疗治疗充血性心衰的疗效。方法:78例充血性心衰病人随机分为两组:培哚普利组40例,男22例,女18例;年龄(63土4)岁。卡托普利组38例,男21例,女17例;年龄(62土6)岁。在常规抗心衰治疗的基础上,培哚普利组用培哚普利2mgqd渐增至4mgqd,卡托普利组用卡托普利6.25mgTid渐增至25mgTid治疗观察3个月。结果:培哚普利组心功能改善情况明显优于卡托普利组(P<0.01)。结论:培哚普利治疗充血性心衰的疗效和耐受性优于卡托普利。     

高压氧对不同体积脑梗死患者血清可溶性细胞间黏附分子-1含量的影响

目的:探讨高压氧(HBO)治疗对不同体积脑梗死患者血清可溶性细胞间黏附分子-1(sICAM-1)含量的影响及临床疗效观察.方法:采用酶联免疫吸附法对20例健康人(对照组)、50例HBO加常规治疗组(HB0组)和50例常规治疗组(常规组)的急性脑梗死患者在入院1、7、14d进行血清sICAM-1含量的动态监测,按病灶大小分大、中、小不同体积梗死组,并进行组间比较;于入院1、14 d对神经功能缺失进行评分,评价患病两组疗效差异.结果:入院1 d时大体积组脑梗死患者血清sICAM.1含量高于中、小体积组,中体积组高于小体积组(P＜0.01).各体积组血清sICAM-1含量均高于对照组(P＜0.01).入院7、14 d,HBO组与常规组各梗死体积组内患者血清sICAM-1含量逐渐降低,2个时间点相比差异有显著性(P＜0.01).入院1 d HBO各体积组与常规组对应体积组比较,血清sICAM-1含量差异无显著性,而7、14 d,该指标均低于对应体积和时间点的常规组(P＜0.01),除了7d时HBO大体积组sICAM-1含量较常规组的太体积组无明显差异.入院14 d HBO组神经功能缺失评分明显低于常规组,两组总有效率差异有显著性(P＜0.05).结论:脑梗死患者血清sICAM-1含量与梗死体积密切相关.HBO治疗能降低不同体积脑梗死患者血清sICAM-1的含量,减轻炎症损伤.提高临床疗效.     

贝前列素钠对早期糖尿病肾病患者血清可溶性细胞间黏附分子1、C反应蛋白及尿微量白蛋白排泄率影响的临床观察

目的 观察贝前列素钠对早期糖尿病肾病(DN)患者的临床疗效.方法 测定27例糖尿病无肾病患者(糖尿病无肾病组)、48例早期DN(DN组)患者血清可溶性细胞间黏附分子1(sICAM-1)浓度,并将48例早期DN患者随机分为两组,常规治疗组和贝前列素钠治疗组,各24例,测定两组治疗前后sICAM-1、C反应蛋白(CRP)及尿微量白蛋白排泄率(UAER)的变化.结果 早期DN患者血清sICAM-1浓度[(1385±171) g/L与(943±167) g/L;t=1.034,P=0.002]明显高于糖尿病无肾病组.贝前列素钠治疗组与常规治疗组治疗前血浆sICAM-1、CRP及UAER浓度比较差异均无统计学意义(P均＞0.05),治疗后均较治疗前改善,差异均有统计学意义(P＜0.05或P＜0.01),且贝前列素钠治疗组较常规治疗组改善明显,差异均有统计学意义(P＜0.05或P＜0.01).结论 早期DN患者即存在血清sICAM-1浓度升高,贝前列素钠治疗显著降低早期DN患者血清sICAM-1、CRP及UAER浓度,对早期DN有保护作用.     

Genetic polymorphism of cytochrome P450 1A1 (Cyp1A1) and glutathione transferases (M1, T1 and P1) among Africans.

The co-ordinate expression and regulation of the drug metabolising enzymes, cytochrome P4501A1 (CYPlAl) and glutathione transferases (GSTM1, GSTT1 and GSTP1), and their metabolic balance in the cells of target organs may determine whether exposure to carcinogens results in cancer. Besides showing variability in activity due to induction and inhibition, these enzymes also exhibit genetic polymorphism that alter enzyme levels and activity. We determined frequencies of common allelic variants of CYP1A1 and glutathione (M1, T1 and P1) among Tanzanians, South African Venda and Zimbabweans using PCR/restriction fragment length polymorphism techniques. The CYP1A1 Val462 mutant variant was found at a frequency of 1.3% among 114 subjects. The GSTM1*0 genotype was found at a frequency of 29% and 33% among Tanzanian psychiatric patients and healthy volunteers, respectively. Similarly, the GSTT1*0 polymorphism was present with a frequency of 25% in both the psychiatric patients and healthy controls. The frequency of GSTP1 Val105 variant was 16%, 12% and 21% among Tanzanians, South African Venda and Zimbabweans, respectively. We conclude here that CYP1A1 Val462 polymorphism is very rare among Africans. This is the first report of the GSTP1 Val105 variant frequency in African populations. We show here that there are no differences in frequencies of the variant alleles for CYP1A1, GSTM1, GSTT1 and GSTP1 in the three African populations.     

子宫内膜癌中CYP1A1，CYP1B1及COMT mRNA的表达及临床意义

[目的]探讨细胞色素P450酶（CYP）1A1, 1B1和儿茶酚-O-甲基转移酶（COMT） mRNA的表达与子宫内膜癌发生发展的关系.[方法]采用RT-PCR方法检测48例子宫内膜癌患者和53例健康对照个体的外周血淋巴细胞中CYP1A1,CYP1B1和COMT mRNA的表达.[结果]子宫内膜癌患者外周血淋巴细胞中CYP1A1,CYP1B1 mRNA的表达明显增高,经Logistic回归分析后, CYP1B1 mRNA的高表达能增加子宫内膜癌的发病风险,进一步分析显示Ⅱ期子宫内膜癌CYP1B1 mRNA的表达高于Ⅰ期患者,差异具有显著性意义.[结论]外周血淋巴细胞中CYP1B1 mRNA的高表达与子宫内膜癌的发生发展密切相关.     

周期蛋白D_1,B_1在子宫颈癌中的表达及其与临床病理间的关系

目的探讨CyclinD1,CyclinB1在子宫颈癌中的表达及其与临床病理间的关系。方法收集哈尔滨医科大学附属四院收治的38例子宫颈癌组织。采用S-P免疫组织化学法,选用CyclinD1,CyclinB1多克隆抗体,分别检测其在38例子宫颈癌中的表达率。结果 CyclinD1在38例子宫颈癌中的阳性表达率为76.32%,CyclinB1的阳性表达率为52.63%,CyclinD1的表达率高于CyclinB1,并且其表达差异有统计学意义(经Fisher确切概率法,P<0.05)。CyclinD1,CyclinB1两者的阳性表达率与淋巴结有无转移之间的关系:Cy-clinD1高于CyclinB1,但差异无统计学意义(经Fisher确切概率法,P>0.05)。结论 CyclinD1驱动细胞由G1期进入S期,促进细胞增殖,决定细胞周期进程的速度和方向,在子宫颈癌的发展过程中起着主要的作用。CyclinB1是在有丝分裂过程中起调控作用的周期蛋白,受着cyclinD1作用的影响。     

骨髓增生异常综合征患者GSTT1、GSTM1基因分布频率和NQO1基因多态性分析

目的探讨谷胱甘肽S转移酶（GST）基因T1、M1（GSTY1、GSTM1）和苯醌氧化还原酶基因（NQO1C609T）多态性与骨髓增生异常综合征（MDS）易感性及MDS染色体核型异常的关系。方法用多重PCR方法检测52例MDS患者和241名与患者无血缘关系的正常人GSTF1和GSTM1基因型，用PCR-限制性片段长度多态性（RFLP）方法分析NQO1C609T基因型。结果与正常人对照组相比，MDS患者GSTT1和GSTM1无效型（nu11）比例明显增高（P值均〈0．01），其比值比（OR）分别为2．873（95％可信区间：1．491～5．537）和3．591（95％可信区间：1．717～7．508）。染色体核型正常的MDS患者GSTT1无效型比例较正常人对照组显著增高（OR=5．336，P〈0．01），而GSTM1无效型比例与正常人对照组比较差异无统计学意义染色体核型异常的MDS患者GSTM1无效型比例较正常人对照组显著增高（OR=3．740，P〈0．01），而GSTT1无效型比例与正常人对照组比较差异无统计学意义MDS患者的NQI1C609T各基因型与正常人对照组差异无统计学意义。结论GSTT1和GSTM1基因无效型可能与MDS发生相关，对判断MDS患者是否出现染色体核型异常有一定意义。     

吸烟和CYP1A1、GSTM1基因多态对肺癌易感性影响

目的:探讨细胞色素P4501A1(cytochrome P-450 1A1,CYP1A1)与谷胱甘肤硫转移酶M1(glutathione S-transferase M1,GSTM1)基因多态与支气管肺癌的关系.方法:采用PCR限制性片段多态检测法,检测肺癌组103例和正常对照组138例患者的CYP1A1与GSTM1基因多态,以非条件性Logistic回归模型分别对年龄、性别进行校正后计算优势比及95%CI.结果:CYP1A1 ml突变型等位基因频率在对照组和肺癌组分别为27.6%和42.7%;GSTM1的缺陷型基因(D)频率在对照组、肺癌组分别为44.2%和61.2%.Logistic回归分析表明,CYP1A1(w1/m1)杂合型(B型)患肺癌的升高3.19倍,纯合突变型(C型)基因患肺癌的升高2.61倍,GSTM1缺陷型(D)患肺癌危险度升高2.09倍,差异均有统计学意义(P<0.05).GSTMl(D)/CYP1A1(B或C)基因型的个体患肺癌危险度为5.72倍.GSTMI(D)和CYP1A1 ml突变型等位基因均可明显增加鳞癌和小细胞癌的患病危险度.结论:CYP1A ml突变型等位基因和GSTM1(D)均是患肺癌的危险因素.CYP1A m1突变型等位基因和GSTM1(D)存在明显的交互作用,二者与吸烟有协同作用.     

Vectorial transport of enalapril by Oatp1a1/Mrp2 and OATP1B1 and OATP1B3/MRP2 in rat and human livers

Although Oatp1a1 (rat organic anion-transporting polypeptide 1a1) was the transporter found responsible for the hepatocellular entry of enalapril (EN) into the rat liver, the canalicular transporter involved for excretion of EN and the metabolite, enalaprilat (ENA), was unknown. The Eisai hyperbilirubinemic rat (EHBR) that lacks Mrp2 (multidrug resistance-associated protein 2) was used to appraise the role of Mrp2 in the excretion of [3H]EN and its metabolite [3H]ENA in single-pass rat liver preparations. Although the total and metabolic clearances and hepatic extraction ratios at steady-state were virtually unaltered for EN in EHBR compared with published values of Sprague-Dawley rats, the biliary clearances of EN and ENA were significantly reduced almost to zero (P<0.05). Involvement of human OATP1B1, OATP1B3, and MRP2 in EN transport was further assessed in single- or double-transfected mammalian cells. Human embryonic kidney 293 cells that expressed OATP1B1 or OATP1B3 showed that OATP1B3 transport of EN (20-500 microM) was of low affinity, whereas transport of EN by OATP1B1 was associated with the Km of 262+/-35 microM, a value similar to that for Oatp1a1 (214 microM). The transcellular transport of EN via human OATP1B1 and MRP2, investigated with the double-transfected Madin-Darby canine kidney (MDCK) II cells in the Transwell system, showed that the sinusoidal to canalicular flux of EN in the OATP1B1/MRP2/MDCK cells was significantly higher (P<0.05) than that of mock/MDCK and OATP1B1/MDCK cells. EN was transported by Oatp1a1 and Mrp2 in rats and OATP1B1/OATP1B3 and MRP2 in humans.     

Sequences of the NPS-1 and TLE-1 beta-lactamase genes

The NPS-1 and TLE-1 beta-lactamase genes were cloned and sequenced. NPS-1 differed from LCR-1 beta-lactamase in 8 of 260 amino acids. TLE-1 differed from TEM-1 by a single Asp(115)-->Gly substitution and has been renamed TEM-90.     

ABCA1, ABCG1, and SR-BI: Transit of HDL-associated sphingosine-1-phosphate

Sphingosine-1-phosphate (S1P) is a zwitterionic lysophospholipid generated by the sphingosine kinase-catalyzed phosphorylation of sphingosine. A number of the biological effects of S1P are mediated by its binding to five specific G protein-coupled receptors located on the cell surface or intracellular targets. However, the synthesis and secretion of S1P require release out of cells for binding with receptors by certain transporters and carriers. High-density lipoprotein (HDL) is an important carrier of S1P in the blood, but the mechanism by which it does so is unclear. This review discusses the mechanism how S1P is transported, and focuses particularly on how the formation of HDL-associated S1P (HDL-S1P) is mediated by certain transporters and carriers. A hypothesis that the ATP-binding cassette transporter A1 (ABCA1), ABCG1, and scavenger receptor class B memberI (SR-BI) play pivotal roles in HDL-S1P formation is also described.