不同剂量卡维地洛干预对心肌梗死后心力衰竭大鼠心肌细胞凋亡和凋亡相关基因表达的影响

目的 :探讨不同剂量卡维地洛 (CAR)对心肌梗死 (MI)后大鼠心肌细胞凋亡的影响及CAR治疗充血性心力衰竭 (CHF)的作用机制。方法 :将雄性Waistar大鼠前降支结扎 ,于术后 1周开始分别予大剂量CAR[HCAR组 ,6 0mg/ (kg·d) ]和小剂量CAR[LCAR组 ,6mg/ (kg·d) ]干预 7周 ,观察不同剂量CAR对大鼠血流动力学参数、心肌细胞凋亡、Fas、Fas配体 (FasL)和Bcl 2mRNA表达的影响。结果 :CAR可改善心功能指标 ,降低心肌细胞凋亡指数、Fas及FasL的mRNA水平 ,上调Bcl 2表达 ,其中对心肌细胞凋亡指数、Fas及Bcl 2mRNA表达的影响以HCAR组明显。结论 :CAR可有效地减少MI后心肌细胞凋亡 ,防治CHF ,效果以大剂量明显 ,这可能与其对凋亡相关基因表达影响的差异有关     

通心络对家兔动脉粥样硬化合并急性心肌梗死的保护作用及其机制

目的研究通心络对家兔实验性动脉粥样硬化合并急性心肌梗死的保护作用,探讨其可能的作用机制。方法采用高脂饮食建立家兔动脉粥样硬化模型。27只造模成功的家兔随机分成3组,每组9只,分别为安慰剂组（A组）、通心络组（B组）和阳性对照组（c组）。A组予以安慰剂,B组予以通心络0．5g-kg-1d。＋阿司匹林10mg·kg-1·d-1＋阿托伐他汀5mg·kg＋d-1;c组予以阿司匹林10mg·kg-1·d-1＋给药期间普通饮食。各组在常规剂量药物干预1周后以3倍常规剂量的负荷剂量药物干预3h,建立急性心肌梗死模型。急性心肌梗死模型造模成功4h后处死家兔,取心脏标本制作病理切片,观察病理形态学改变。应用免疫组化方法检测缺血心肌组织细胞凋亡相关蛋白Bcl一2、Bax的表达水平;应用TUNEL技术检测心肌细胞凋亡指数。结果与A组比较,B组和c组Bax蛋白的表达水平均显著降低（RO．05）,B组Bax蛋白的表达水平最低,Bcl-2蛋白的表达则反之,B组和c组Bcl-2蛋白的表达水平均显著升高（P〈0．05）,B组Bcl-2蛋白的表达水平最高;与A组比较,B组和c组心肌细胞凋亡指数下降,但B组心肌细胞凋亡水平明显减轻（P〈0．05）。结论通心络可以通过调节凋亡相关蛋白Bax及Bcl-2的表达,减少缺血心肌组织心肌细胞凋亡,对心肌梗死有保护作用。     

普罗布考对心肌梗死大鼠心肌组织Bcl-2和Bax表达及氧化应激的影响

背景 心肌梗死后心肌细胞凋亡与氧化应激有关,普罗布考为脂溶性强抗氧化剂,实验证明具有保护心肌细胞的作用,该药保护心肌细胞的作用是否通过调控细胞凋亡相关基因Bcl-2和Bax目前尚不清楚.目的 研究普罗布考对心肌梗死大鼠心肌组织Bcl-2和Bax表达及氧化应激的影响.方法 将心肌梗死后24 h存活大鼠41只随机分为2组:盐水组(5 mL/d,n=20),普罗布考组[60 mg/(kg·d),n=21],灌胃给药;另设假手术组(n=12)作对照.分别于心肌梗死后6周:导管法测定左室有创血流动力学指标,TUNEL法检测非梗死区心肌细胞凋亡;RT-PCR的方法观察心肌组织Bcl-2及Bax mRNA表达的变化;Western blot检测心肌Bcl-2及Bax蛋白表达;比色法测定心肌组织氧化代谢指标.结果 (1)与假手术组相比,所有心肌梗死大鼠均出现显著的Bcl-2 mRNA及蛋白表达降低,Pax mRNA及蛋白表达与心肌细胞凋亡指数显著升高(P均＜0.01).与盐水组相比,普罗布考组心肌组织Bcl-2 mRNA及蛋白表达显著升高,Bax mRNA及蛋白表达及心肌细胞凋亡指数显著降低(P均＜0.01);(2)与假手术组相比,所有心肌梗死大鼠心肌组织均出现显著的MDA升高,SOD、TAOC含量及SOD/MDA比值降低(P均＜0.01);与盐水组相比,普罗布考组MDA显著下降,SOD、TAOC含量及SOD/MDA均升高(P均＜0.01);心肌细胞凋亡指数与TAOC、SOD/MDA比值呈负相关(P均＜0.01).结论 心肌梗死后心肌细胞凋亡增加,普罗布考治疗可以抑制心肌细胞凋亡,降低心肌梗死后心肌组织的氧化应激.     

卡维地洛对心衰大鼠心肌细胞凋亡及NF-κB活性的影响

目的：探讨核因子-κB（NF-κB）活化与充血性心力衰竭大鼠心肌细胞凋亡的关系及卡维地洛（CAR）的作用机制。方法：观察雄性Waistar大鼠心肌梗死（MI）8周后的心肌细胞凋亡指数、心肌总抗氧化能力、丙二醛的浓度、Fas和FasL的mRNA水平、KB抑制蛋白-α（I-κB-α）表达及NF-κB的核结合活性的改变，并于MI后1周对大鼠进行7周的CAR和美托洛尔（MET）干预，观察CAR和MET对上述指标的影响。结果：MI后心肌细胞凋亡指数、丙二醛水平、Fas和FasL的mRNA水平、NF-κB活性增高，I-κB-α表达下调、总抗氧化能力下降（P〈0．05）。CAR和MET可不同程度地改善心功能指标（P〈0．05），CAR降低心肌细胞凋亡指数、丙二醛浓度、Fas和FasL表达及升高总抗氧化能力的效果优于MET，并上调I-κB-α表达、显著降低NF-κB活性（P〈0．05）。结论：氧化应激可激活NF-κB，启动Fas和FasL转录，介导心肌细胞凋亡，促进MI后充血性心力衰竭的发生、发展。CAR具有抗氧化作用，可通过抑制I-κB-α降解、降低心肌NF-κB活性，减少心肌细胞凋亡。     

心肌细胞凋亡和NF-κB在卡维地洛改善大鼠心梗后心功能不全中的作用

目的观察卡维地洛对大鼠心肌梗死后心功能不全的作用,并探讨其对心肌细胞凋亡和NF-κB激活的影响,进一步阐明卡维地洛的作用机制。方法雄性SD大鼠左冠前降支永久结扎建立心肌梗死后心功能不全模型。24h后存活的大鼠随机分为心肌梗死组和卡维地洛治疗组（10mg.kg-1.d-1灌胃）,并以假手术组为对照。8w后以血流动力学测定判断心功能情况,TUNEL染色法检测心肌细胞凋亡和免疫组化法测定心肌细胞核阳染率以反映心肌细胞NF-κB的激活情况。结果心肌梗死组平均动脉压（MBP）,＋dp/dt均显著低于假手术组,左室舒张末期压力（LVEDP）值较假手术组明显增高,提示形成了心功能不全。卡维地洛治疗组的左室/体重较心肌梗死组明显降低;卡维地洛治疗组的胶原含量CVF（%）较心肌梗死组明显降低。卡维地洛治疗后显著减少了心肌肥厚、心肌纤维化程度和改善了心功能。卡维地洛显著减少了心肌细胞凋亡,增加了NF-κB的激活。结论心肌细胞凋亡和NF-κB的激活参与了大鼠心肌梗死后心室重塑和心功能不全的发生。卡维地洛改善心室重塑和心功能的作用与减少心肌细胞凋亡和增加心肌细胞NF-κB的激活有关。     

银丹心脑通软胶囊对大鼠急性心肌梗死后Bcl-2、Bax水平的影响

目的探讨银丹心脑通软胶囊对急性心肌梗死(AMI)大鼠Bcl-2、Bax水平的影响。方法结扎冠脉前降支建立AMI模型,将造模成功大鼠随机分为模型组、银丹心脑通大剂量组(1.6 g·kg-1·d-1)、银丹心脑通小剂量组(0.8 g·kg-1·d-1)、阳性药对照卡托普利组(5 mg·kg-1·d-1)各12只,假手术组10只。术后第2天开始灌胃给药,模型组与假手术组给予同等剂量生理盐水,连续4 w。RT-PCR检测非梗死区心肌Bcl-2、Bax mRNA的表达,TUNEL法计算心肌细胞凋亡指数。结果与模型组比较,各给药组的凋亡指数及左室梗死范围明显降低(P<0.05),左心室非梗死区Bax mRNA的表达明显减少(P<0.05),Bcl-2 mRNA的表达明显增加(P<0.05)。结论银丹心脑通软胶囊能够降低AMI后心肌细胞凋亡指数,减少梗死面积,减少左心室非梗死区Bax mRNA的表达,上调Bcl-2 mRNA的表达,提示银丹心脑通软胶囊可通过抑制凋亡通路Bax/Bcl-2改善梗死后心肌细胞凋亡。     

阿托伐他汀早期干预对急性心肌梗死心肌细胞凋亡的影响

目的探讨不同剂量阿托伐他汀提早干预治疗,对兔急性心肌梗死(AMI)细胞凋亡的影响。方法24只新西兰兔随机分为3组:①对照组:不予药物干预;②低剂量组:0.5mg·kg-1·d-1阿托伐他汀;③高剂量组:5mg·kg-1·d-1阿托伐他汀。在药物干预3d后制作AMI模型,检测心肌梗死及其边缘区细胞凋亡率并观察心肌Bax和Bcl-2表达。结果①高剂量组心肌细胞凋亡率明显低于对照组和低剂量组(P<0.05,P<0.01)。②高剂量组Bcl-2表达高于对照组及低剂量组(P<0.01,P<0.05),对照组与低剂量组差异无统计学意义;三组Bax表达均较高,但组间比较,差异无统计学意义。③Pearson线性相关分析显示梗死及其边缘区心肌细胞凋亡率与相应区域Bcl-2表达呈负相关,与心肌组织Bax表达无明显相关关系。结论高剂量阿托伐他汀降低梗死区及其边缘区心肌细胞凋亡率,与低剂量相比显示出更好保护作用。     

番茄红素对高脂血症大鼠主动脉的保护作用

目的研究番茄红素对高脂血症大鼠主动脉的保护作用。方法 64只SD成年雄性大鼠按体重和总胆固醇(TC)水平随机分为对照组、模型组、氟伐他汀钠10 mg·kg-1·d-1、番茄红素4.4、11、22、44、110 mg·kg-1·d-1共8个剂量组;对照组喂基础饲料,其余饲高脂饲料;第2、3周,对照组和模型组行1%羧甲基纤维素钠(CMC-Na)灌胃,其余以1%CMC-Na为溶剂按确定剂量灌胃。实验期间,采尾血检测TC、甘油三酯(TG)、高密度脂蛋白-胆固醇(HDL-C)、低密度脂蛋白-胆固醇(LDL-C)、超氧化物歧化酶(SOD)、丙二醛(MDA),并计算动脉硬化指数(AI)及血浆致动脉硬化指数(AIP)。光镜下观察主动脉弓病理变化,并以番茄红素各剂量组血液各项指标与模型组差值的绝对数进行曲线拟合分析。结果与模型组相比,各干预组血清TC、TG、LDL-C、MDA、AI、AIP降低,SOD活性增强;主动脉弓管壁泡沫细胞堆积减轻;番茄红素44 mg·kg-1·d-1组大鼠血清LDL-C、MDA分别为(0.73±0.04)mmol/L、(3.14±0.06)nmol/ml,改善程度强于氟伐他汀钠组。经曲线拟合得到5个曲线方程。结论番茄红素可降低高脂血症大鼠血脂,提高机体抗氧化能力,减轻主动脉病变,剂量为44 mg·kg-1·d-1时其作用强于氟伐他汀钠;采用拟合曲线方程可初步了解在4.4~110 mg·kg-1·d-1剂量范围的番茄红素对高脂血症大鼠血液各指标改变均有影响。     

四逆汤与福辛普利预处理对急性心肌梗死大鼠氧化应激的影响

目的探讨四逆汤与福辛普利预处理及其二者联合用药预处理对大鼠急性心肌梗死(AMI)氧化应激的影响。方法四逆汤(5 ml·kg-1·d-1)和福辛普利(20 mg·kg-1·d-1)分别全剂量灌胃以及两药半剂量联合(四逆汤2.5 ml·kg-1·d-1+福辛普利10mg·kg-1·d-1)灌胃,连续3 d后结扎冠状动脉前降支复制AMI大鼠模型。同时设立假手术组和模型组。观察在AMI后血清超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性及丙二醛(MDA)含量的变化以及血清和心肌组织血管紧张素(Ang)Ⅱ的变化。结果单独应用全剂量的四逆汤或福辛普利与四逆汤和福辛普利减半剂量联合预处理用药均可明显降低AMI大鼠血清MDA含量,增强SOD及GSH-Px活性,而两药联合应用时,其抗氧化的作用明显强于单药(P<0.05);福辛普利可明显降低血清及心肌组织AngⅡ含量,而四逆汤降低AngⅡ的作用弱于福辛普利(P<0.05),联合用药组介于二者之间。结论四逆汤与福辛普利均能增强机体抗氧化作用,抑制脂质过氧化反应,两药联合应用时效果优于单药;福辛普利的抗氧化活性主要与抑制肾素-血管紧张素系统(RAS)有关,四逆汤可能另有他因。     

三七总皂苷与卡维地洛改善心肌梗死后大鼠心功能的作用

目的用不同浓度三七总皂苷（panaxnotoginsengsaponin,PNS）和卡维地洛干预急性心肌梗死（acutemyocardialinfarction,AMI）大鼠,评价其改善心功能作用的疗效。方法建立大鼠AMI模型84只,随机分为心肌梗死对照组（AMI组）,PNS治疗低（PNS．L,20mg·kg-1·d-1）、中（PNS．M,40mg·kg-1·d-1）、高（PNS—H,80mg·kg-1·d-1）3组,卡维地洛治疗低（CARV．L,2．5mg·kg-1·d-1）、中（CARV—M,5mg·kg-1·d-1）、高（CARV—H,10mg·kg-1·d-1）3组,另设假结扎组（sham组）,每组12只。灌胃给药4周后,用小动物超声心动图仪检测心功能,检测血浆心力衰竭标志物N-末端脑钠肽前体（N—terminalpro—brainnatriureticpeptide,NT—pro．BNP）浓度,并行心肌组织的苏木素-伊红染色分析。结果同sham组比较,AMI组左心室射血分数和左心室收缩百分率、左心室前壁舒张期厚度、左心室前壁收缩期厚度均明显降低,差异有统计学意义（P〈0．01）;左心室舒张末期内径、左心室收缩末期内径及血浆NT—pro—BNP浓度显著增高,差异有统计学意义（P〈0．01）。同AMI组比较,PNS和卡维地洛治疗的中、高剂量组左心室射血分数、左心室收缩百分率、左心室前壁舒张期厚度、左心室前壁收缩期厚度均明显增加,而左心室舒张末期内径和左心室收缩末期内径及血浆NT—pro．BNP浓度明显降低,差异有统计学意义（P〈0．01）。而且,各治疗组的心肌组织细胞均得到较好的保护。结论用PNS和卡维地洛治疗AMI大鼠4周均能有效保护心肌组织和改善心功能,减缓心力衰竭的发生、发展,且PNS效果略优。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.