细胞凋亡与肺缺血再灌注损伤的关系及川芎嗪的影响

目的:探讨兔肺组织细胞凋亡和肺缺血再灌注损伤的关系及川芎嗪的影响。方法:制备兔在体原位肺缺血再灌注损伤模型(PIRI),应用末端脱氧核苷酸转移酶(TdT)介导的dUTP缺口末端标记技术(TUNEL)检测缺血再灌注损伤所引起的肺细胞凋亡的变化;采用Murata法进行肺组织损伤定量(IQA)检测,进行细胞凋亡与IQA的相关性分析。结果:肺缺血再灌注后,缺血再灌注组(IR组)1、3和5 h发生明显的肺细胞凋亡,凋亡细胞数峰值位于再灌注3 h(P<0.01),而川芎嗪干预细胞凋亡指数与同一时相缺血再灌注组比较显著降低(P<0.05,P<0.01);IR组肺组织IQA值高于TMP组(P<0.01);细胞凋亡指数与肺组织损伤定量指标呈正相关(r=0.718,P<0.01)。结论:细胞凋亡在肺缺血再灌注损伤机制中可能发挥着重要作用,川芎嗪可减轻肺缺血再灌注导致的细胞凋亡。     

联合应用化疗药物对三氧化二砷耐药白血病细胞的毒性实验研究

目的:探讨化疗药物联合应用对三氧化二砷(As2O3)耐药白血病细胞(K562/AS2)的毒性作用。方法:细胞毒实验采用MTT法,二药合用时细胞毒性作用采用ChouTalalay联合指数法分析,细胞表面P糖蛋白(Pgp)和细胞内柔红霉素(DNR)浓度测定采用流式细胞术测定。结果:K562/AS2细胞对三氧化二砷、柔红霉素、鬼臼乙叉苷(VP16)、三尖杉酯碱(H)、米托蒽醌(NVT)和阿糖胞苷(AraC)的耐药倍数分别为7.4、2.9、3.8、3.6、2.8和1.1。K562细胞和K562/AS2细胞的细胞表面Pgp或细胞内任意荧光强度无显著的统计学意义(P>0.05)。As2O3与DNR、VP16、H或NVT联合应用时,对K562、K562/AS2和Pgp表达的白血病细胞(K562/A02)细胞的联合指数均大于1。异搏定与DNR联合应用时,对K562和K562/AS2细胞的联合指数均大于1,但是对K562/A02细胞的联合指数均小于1。结论:K562/AS2细胞对As2O3、DNR、VP16和NVT耐药,其机制与Pgp表达无关。异搏定联合应用DNR可以逆转K562/A02对DNR的耐药性,不能逆转DNR对As2O3耐药细胞的耐药性。As2O3与DN、VP16、H和NVT联合应用时,对K562、K562/AS2和K562/A02细胞的毒性均为拮抗作用。     

血清抵抗素与2型糖尿病胰岛素抵抗关系的研究

目的探讨抵抗素在2型糖尿病胰岛素抵抗发生中的作用。方法测量42例2型糖尿病患者及40例健康对照者的身高、体重、腰围,计算体重指数,酶联免疫吸附法测空腹血清抵抗素浓度。同时测定空腹胰岛素、空腹血糖、血脂的水平,根据Homa模型提出的公式,计算出胰岛素抵抗指数并分析各指标间的关系。结果2型糖尿病组抵抗素的水平显著高于对照组(P<0.01);血清抵抗素水平与胰岛素抵抗指数(IR)、空腹血糖、腰围呈显著正相关。结论抵抗素参与了胰岛素抵抗的发生,与糖尿病的发生、发展密切相关,可作为评价胰岛素抵抗程度的一项指标。     

罗格列酮联合胰岛素治疗2型糖尿病的临床疗效观察

目的观察罗格列酮应用于单用胰岛素治疗血糖控制欠佳的2型糖尿病患者的疗效及安全性。方法102例2型糖尿病患者,随机分成两组:单用胰岛素治疗组(DM+INS组)50例,联合治疗组(DM+INS+RSG组)治疗组52例,在继续应用胰岛素治疗的基础上加服罗格列酮(Rosiglitazone,RSG)4mg/d,共三个月。观测两组治疗前后空腹血糖(FPG)及餐后血糖(PPG)、糖化血红蛋白(HgA1C)、甘油三酯(TG)、胆固醇(TC)、高密度脂蛋白(HDLC)、低密度脂蛋白(LDLC)和体重指数(BMI)的改变。结果DM+INS+RSG组与DM+INS组治疗前FPG、PPG、HbA1C、TC、TG、HDLC、LDLC和胰岛素用量无明显统计学差异(P>0.05)。DM+INS+RSG组治疗后1个月和3个月FPG、PPG、HbA1C均有明显的下降(P<0.05,P<0.01)。结论对单用胰岛素治疗血糖控制欠佳的2型糖尿病患者可加用胰岛素增敏剂罗格列酮治疗,可使血糖和糖化血红蛋白得以良好的控制。     

炎症因子与胰岛素抵抗和2型糖尿病大血管病变的相关性研究

目的探讨炎症因子C-反应蛋白（CRP）与胰岛素抵抗（IR）和2型糖尿病（T2DM）大血管病变的关系。方法用颗粒增强免疫沉淀法测定T2DM合并大血管病变（70例）、T2DM无大血管病变（60例）及正常对照组（90名）的血清超敏CRP（usCRP）水平变化；用HOMA—IR模型作为估计IR的指标；将CRP与HOMA—IR、空腹胰岛素（FINS）、同型半胱氨酸（Hcy）、空腹血糖（FBG）、体重指数（BMI）、腰臀比（WHR）、甘油三酯（TG）等作相关分析。结果T2DM合并大血管病变组血清usCRP水平明显高于T2DM无大血管病变组及正常对照组（P〈0．01），T2DM无大血管病变组高于正常对照组（P〈0．01）。当调整SBP、FBG、TG、WHR等因素的影响后，协方差结果显示usCRP在T2DM合并大血管病变组仍高于T2DM无大血管病变组及正常对照组（P〈0．05），T2DM无大血管病变组高于正常对照组（P〈0．05）。在T2DM合并大血管病变组，Person相关分析显示，usCRP与FINS、HOMA-IR、TG呈正相关（P值分别〈0．05、〈0．01和〈0．05），与Hcy等无关。逐步线性回归结果显示，TG、HOMA—IR是影响CRP的主要因素。结论CRP可能是T2DM和T2DM大血管病变的危险因子，CRP可能通过胰岛素抵抗参与了T2DM大血管病变的发生和发展。     

Weight cycling did not increase tumor incidence in high fat–fed rats treated with a low-dose 7,12-dimethylbenzyl(1)anthracene

The present study tested the hypothesis that weight cycling (WC, repeated weight gain and loss) increases the tumorigenesis in rats exposed to carcinogen. Female Wistar rats consumed a high-fat diet (35% weight per weight) and were divided: (1) ad lib–fed rats that were treated with 7,12-dimethylbenzyl(1)anthracene (DMBA, 2 mg) at 55 days of age (AL-DMBA); (2) WC rats that were treated with DMBA (WC-DMBA); and (3) vehicle-treated WC rats (WC-VEH). In this study, WC did not alter blood parameter concentrations and did not influence insulin sensitivity. Mammary tissue F₂-isoprostane concentrations were lowest in WC-VEH and highest in AL-DMBA groups. Tumor incidence and burden were similar among all groups. The data obtained from this study do not support our hypothesis. This may be due to low dose of DMBA used, strain and age of the rats, number of WC cycles, and the amount of trans–fatty acids in the diets.     

红景天注射液对麻醉犬心脏血流动力学及心肌耗氧量的影响

目的:研究红景天注射液治疗冠心病的药理作用及作用机制。方法:将实验犬20只,随机分为空白对照组、阳性药对照组和红景天注射液小、大剂量组。经戊巴比妥钠30mg·kg^-1静脉麻醉后开胸,分别测定冠脉血流量、心输出量、左室内压、左室内压上升最大速率(dp/dt_max)、冠状静脉窦血氧含量、动脉血氧含量、心肌耗氧量、心搏出量、耗氧指数、心脏指数、冠脉阻力、总外周阻力及氧利用率等。结果:动物静脉注射红景天注射液后,冠脉阻力、动脉血压、总外周阻力、耗氧指数、心肌耗氧量、心率明显降低,心输出量、心搏出量及冠状静脉窦血氧含量明显上升,与药前及空白对照组比较均有显著性差异(P<0.05-0.01);左室内压和心肌收缩力则无明显改变。结论:结果表明,用红景天注射液可扩张冠脉血管、降低心脏后负荷,在不明显增加心肌收缩力和左心室压力的情况下,心输出量和每博出量明显增加,心脏有效作功得到加强;还能使冠状静脉窦血氧含量显著增加,心肌耗氧指数降低,心肌耗氧量下降,从而改善心肌的供血供氧,调整心脏血管的顺应性,对心血管系统起到调整和改善作用。这可能是红景天注射液治疗冠心病的药理机理。     

Barrier function of porcine choroid plexus epithelial cells is modulated by cAMP-dependent pathways in vitro

In the present paper, we demonstrate that the barrier properties of primary cultured epithelial cells isolated from porcine choroid plexus are regulated by cAMP-dependent signal transduction pathways in vitro. Triggering cAMP-connected cascades in cell layers grown on permeable filters with cAMP-analogues or forskolin led to a significant increase of transepithelial electrical resistances and a pronounced reduction in the permeation rate of a 4 kDa-dextran probe. In dose-response experiments using the cAMP-analogue 8-(4-chlorophenylthio)-cAMP transepithelial electrical resistances were observed to increase above a threshold concentration ranging between 10(-5.5) and 10(-5) M. Additional impedance studies performed with confluent cell layers grown on gold-film electrodes revealed that the observed changes in transepithelial resistances and presumably also in macromolecular permeation rates were not entirely caused by a reinforcement of intercellular junctions but also contained contributions from changes in the cell-substrate adhesion pattern. These inherent contributions to the electrical resistance and macromolecular permeability are caused by a restricted diffusion pathway between basal plasma membrane and culture substrate that have to be considered in data analysis, especially when leaky cell layers on filter substrates with low pore densities are used.     

Low plasma epinephrine in elderly female subjects of dementia of Alzheimer type

One of the robust features of brain pathologies of dementia of Alzheimer type (DAT) is the impairment of the hippocampus, especially the cholinergic system. Several animal studies have suggested that the cholinergic system in the hippocampus is involved in the control of the plasma level of catecholamines and glucose. The stimulation of the hippocampal cholinergic system has resulted in the elevation of plasma catecholamines and glucose in rats. In the present study, we measured the plasma level of epinephrine, norepinephrine, dopamine, glucose, and insulin during a fasting state in the morning in hospitalized DAT (n=66), vascular dementia (VD) (n=28), or non-demented (ND) (n=21) females (mean age DAT=82. 49+/-4.98, VD=82.86+/-5.86, ND=82.95+/-7.77, respectively). Statistical analysis showed that the plasma level of epinephrine during a fasting state in DAT subjects was significantly lower than that of ND subjects; however, in VD subjects the level of epinephrine was not different from that of ND subjects. Other values did not differ significantly among the groups.     

Nitric oxide does not play a major role in the regulation of systemic hemodynamic responses to acute normovolemic hemodilution

Background: The mechanisms of cardiovascular changes following acute normovolemic hemodilution (ANH) have not been fully elucidated. We tested the hypothesis that inhibition of nitric oxide synthesis attenuates ANH-induced cardiovascular responses.
Methods: We observed the effects of N^ω-nitro-L-arginine methyl ester (L-NAME) pretreatment on ANH-induced cardiovascular responses and compared these effects with those elicited by phenylephrine (PHE). Twenty dogs anesthetized with isoflurane were divided into two groups: one group was pretreated with L-NAME and the other with PHE. Both groups were normovolemically hemodiluted using 6% hydroxyethyl starch to reduce the hemoglobin concentration to approximately 50% of the pretreatment value.
Results: Pretreatment with either L-NAME or PHE caused a significant increase in mean aortic blood pressure (MAP) and systemic vascular resistance (SVR) with a significant decrease in cardiac output (CO) and stroke volume (SV). However, no remarkable differences in these variables were seen between groups. In both groups ANH produced increases in heart rate, CO, SV, and maximal left ventricular dP/dt with a significant decrease in SVR. No significant differences in these variables were apparent after ANH except that MAP was decreased in the PHE group but not in the L-NAME group.
Conclusion: Our results suggest that nitric oxide does not play a major role in mediation or modulation of the systemic vascular responses to ANH.