缝隙连接阻滞剂heptanol对缺血所致室性心律失常的影响

目的 观察缝隙连接阻滞剂heptanol对局部心肌缺血性室性心律失常发生率的影响,并探索可能的作用机制.方法 结扎离体SD大鼠冠状动脉前降支,造成左心室前壁局部缺血.观察不同浓度heptanol对缺血所致室性心律失常发生率的影响.记录在0、缺血10、20及30 min各时间点动作电位复极90%时限(MAPD90)、心率、PR间期以及QT间期的变化.结果 heptanol可以明显降低由于缺血引起的室性心动过速(室速)和心室颤动(室颤,缺血组45%;0.1 mmol组10%;0.3 mmol组0;0.5 mmol组0;P＜0.05).heptanol可以降低心率,延长PR间期、QT间期和MAPD90.结论 heptanol可以减少由于局部缺血引起的室速和室颤发生率,这种作用可能与其降低心肌电传导有关.     

缬沙坦对自发高血压大鼠左室心肌心室有效不应期和心室颤动阈值的影响

目的探讨缬沙坦对自发高血压大鼠左室心肌有效不应期和心室颤动(简称室颤)阈值的影响。方法16只10周龄雄性自发高血压大鼠随机分成缬沙坦组和非缬沙坦组,每组8只;8只10周龄Wistar大鼠做为对照组。喂药8周后分别测定各组大鼠动脉收缩压、左室质量指数、心室有效不应期和室颤阈值。结果①非缬沙坦组和缬沙坦组左室质量指数明显大于对照组(3.7±0.02 mg/g,3.2±0.03 mg/g vs 2.5±0.03 mg/g,P<0.001);非缬沙坦组左室质量指数明显大于缬沙坦组(P<0.001);②非缬沙坦组和缬沙坦组室颤阈值明显低于对照组(15.4±0.4 mA,18.6±0.5 mA vs 26.3±0.5 mA,P<0.001);缬沙坦组室颤阈值明显大于非缬沙坦组(P<0.001)。结论缬沙坦通过逆转自发高血压大鼠左室心肌肥厚提高左室心肌室颤阈值。     

柯萨奇B病毒性心肌炎小鼠急性期心肌组织微小RNA1初始体和连接蛋白43的表达

目的观察柯萨奇B病毒性心肌炎小鼠急性期心肌组织微小RNA1初始体(pri-miRNA-1)和连接蛋白43(Cx43)表达变化,探讨病毒性心肌炎(VMC)室性心律失常发生机制。方法40只4周龄雄性Balb/c小鼠随机分为VMC组(n=20)和对照组(n=20)。VMC组小鼠腹腔注射柯萨奇病毒B3(CVB3)Nancy株悬液0.1ml,对照组小鼠腹腔注射不含病毒的RPMI1640培养基0.1ml,分别于接种病毒后第14天无痛苦处死全部小鼠并留取心脏。逆转录-聚合酶链反应(RT-PCR)检测心室肌组织pri-miRNA-1的表达,免疫组织化学法检测Cx43蛋白水平表达,并进行半定量分析。结果①VMC组小鼠心室肌组织pri-miRNA-1表达量明显高于对照组(0.82±0.04vs0.63±0.07,P(0.01);②VMC组小鼠心室肌组织炎症病灶中变性、坏死周围心肌细胞Cx43表达明显减弱,甚至阴性,分布不规则,Cx43蛋白表达明显低于对照组(0.27±0.01vs0.42±0.02,P(0.01);③VMC组小鼠心室肌组织的pri-miRNA-1表达量与Cx43蛋白水平呈显著负相关(r=-0.868,P(0.01)。结论CVB心肌炎小鼠急性期心肌组织pri-miRNA-1表达上调,Cx43蛋白表达下降,miRNA-1可能通过抑制Cx43表达促进室性心律失常的发生。     

交感神经刺激对大鼠缺血性室性心律失常的影响及其机制的探讨

目的 探讨大鼠急性心肌缺血时交感神经刺激对室性心律失常的影响及其潜在的机制.方法 结扎大鼠冠状动脉前降支制备急性心肌缺血模型后随机分组作为心肌缺血组(MI组,n=25)、缺血+交感神经刺激组(MI-SS组,n=25)、交感神经刺激+酚妥拉明+缺血组(MI-SS-Phen组,n=15)、交感神经刺激+普萘洛尔+缺血组(MI-SS-Prop组,n=15)和假手术组(SO组,n=20).心电图监测室性心律失常的发生.蛋白免疫印记法(Western blot)检测缝隙连接蛋白43(Cx43)的磷酸化蛋白及总量表达变化.逆转录聚合酶链反应(PCR)分析Cx43 mRNA的表达变化.免疫荧光观察Cx43表达分布情况.结果 结扎冠状动脉30 min内MI、MI-SS和MI-SS-Phen组分别有1、3和2只大鼠死于心室颤动(室颤);MI-SS组室性心动过速(室速)/室颤发生率(80.0%,20/25)较MI组(52.0%,13/25)明显增加(P＜0.05);与MI-SS组相比,普萘洛尔明显阻断了交感神经刺激促室速/室颤发生的作用(13.3%,2/15,P＜0.05).冠状动脉结扎30 min后,MI组磷酸化Cx43的比例较SO组显著降低(P＜0.05),但其总量并未减少(P＞0.05).与MI组相比,MI-SS组磷酸化Cx43的比例明显增加(P＜0.05),同时其蛋白总量的表达显著降低(P＜0.05);普萘洛尔显著抑制了交感神经刺激导致的Cx43蛋白降解的作用,同时抑制了缺血引起的Cx43脱磷酸化(P＜0.05).MI和MI-SS组Cx43mRNA表达均较SO组显著减少(P＜0.05).免疫荧光结果 显示,与SO组相比,MI组Cx43由端-端连接转化为侧-侧连接,而MI-SS组Cx43分布明显紊乱,不能分辨出Cx43的分布模式.结论 交感神经刺激能够促进室性心律失常的发生,可能主要与β肾上腺素受体的激活从而促进了Cx43的降解有关.     

缝隙连接失耦联剂Heptanol对缺血心肌的影响

研究缝隙连接失耦联剂Heptanol对缺血心肌是否具有类似缺血预处理 (IP)的心肌保护作用 ,进一步探讨IP的心肌保护作用机制。在离体心脏水平 ,观察IP和Heptanol对缺血心肌的影响 ,观测指标 :心率、冠状动脉血流量(简称冠脉流量 )、心律失常情况及心肌梗死范围。结果 :①IP使缺血心肌的心律失常评分下降 ,心肌梗死范围缩小(P <0 .0 1) ,但对冠脉流量和心率没有明显影响 ;②Heptanol使缺血心肌的心律失常评分和心率下降 ,并缩小心肌梗死范围 (P <0 .0 1) ,呈剂量依从性 ,对冠脉流量无明显影响。结论 :①Heptanol可模拟IP的心肌保护作用 ,呈剂量依从性关系 ,但有一定的浓度范围限制 ;②IP的心肌保护作用可能与预处理后细胞间电耦联和代谢耦联下降有关     

缝隙连接阻滞剂Heptanol对缺血介导的室性心律失常的影响

目的研究缝隙连接阻断剂Heptanol对离体大鼠心脏在血流动力学及电生理学方面的作用,及在心肌局部缺血状态下,对于室性心律失常发生率的影响,以进一步探讨缝隙连接在室性心律失常方面的作用机制.方法(1)在离体心脏水平观察不同浓度Heptanol的作用.观测指标Lvsp(左室峰压),Lvdp(左室舒张末压),dp/dtmax(左室压力最大上升速率),MAPD90(动作电位时程),HR(心率),PR间期,QT间期.(2)结扎左冠状动脉前降支,造成再灌注室性心律失常模型,进行心律失常评分.观察Heptanol对于该评分的影响.结果(1)Heptanol可以使心肌的Lvsp,dp/dtmax下降,Lvdp上升,PR间期延长(P＜0.05),并呈剂量依从性.有使MAPD90增加,QT间期延长及心率下降的趋势,但P＞0.05.(2)可使心律失常评分下降(P＜0.01).结论Heptanol可以使正常心肌的收缩功能和顺应性下降,房室传导时间延长.并有使动作电位时程延长,复极时间延长的趋势.Heptanol可以预防缺血心肌的室性心律失常;提示其作用机制可能与它对缝隙连接的阻断有关.     

大鼠心肌缺血预处理及缺血/再灌注损伤模型的改进

目的改进和完善大鼠心肌缺血/再灌注损伤(I/R)模型的制备,简化多次缺血预处理(IP)操作,提高制模成功率。方法成年SD大鼠80只,随机分成四组:改进的缺血/再灌注组及预处理组(PIR,PIP);以往的缺血/再灌注组及预处理组(TIR,TIP)。改进组心电图记录,左颈动脉插管压力测定、TTC染色心肌梗死面积评估。结果①造模成功率:PIR组与TIR组分别为95%和55%(P<0.05);PIP组及TIP组分别为95%和10%(P<0.01)。②PIP组发生心律失常起始时间比PIR组延迟27.1(%P<0.05);室速、室颤持续时间比PIR组分别短77.5(%P<0.01)和68.9(%P<0.05);室速、室颤的发生率分别是PIR组的45(%P<0.05)和30.3(%P<0.05);心律失常得分仅为PIR组的70(%P<0.01)。③颈动脉压力波形的改变。④PIR组及PIP组心肌梗死面积分别为59.4±13.6%和26.8±11.7(%P<0.01)。结论改进的方法能够提高成功率,准确性地复制心肌I/R的实验模型,简化实验操作。     

肾去交感神经对心肌梗死后室性心律失常的影响

目的: 探讨肾去交感神经（RDN）对成年犬心肌梗死后室性心律失常的作用。方法: 8只成年健康比格犬随机分为2组：肾去交感神经组（RDN组，n=4）结扎冠脉前降支构建心肌梗死模型，心肌梗死后1小时给予外科+化学肾去交感神经治疗； 假手术组（Sham组，n=4）结扎冠状动脉，仅开腹分离肾动脉不行肾去交感神经。对比两组犬的室性心律失常发生率（VA）、心室有效不应期（ERP）、测定心室肌交感神经的蛋白表达。结果：心肌梗死 4周，RDN 组的室性早搏数目也较 Sham 组少 [ (350.5±66.92个/24 h 比 525.8±265.96个/24 h，P < 0.05) ]；两组间室速的数目也存在显著差别[ (12.00±6.56个/24 h比30.75±19.52个/24 h，P < 0.05) ]。心肌梗死 4周，RDN组心外膜的有效不应期（ERP）较Sham组延长[ (175±3.5ms 比 143±6.22ms；P < 0.05) ]。与Sham 组比较dERP具有统计学差异( P < 0.05 )，RDN组室颤阈值明显增高[ (5.5 ± 0.65V 比 9.25 ± 1.31V；P < 0.05) ]。RDN组心肌梗死交界区的TH及GAP-43的蛋白表达均显著低于Sham组（P < 0.05）。结论：肾去交感神经可以抑制心肌梗死后室性心律失常的发生，延长心室ERP 和降低dERP，逆转心脏交感神经重构。从而改善心肌梗死交界区电生理特性，RDN预防心肌梗死后室性心律失常的发生，降低心源性猝死的发生。     

缝隙连接蛋白43在老年大鼠缺血性室性心律失常中的作用

目的 探讨缝隙连接蛋白43(Cx43)在老年大鼠心室肌中的表达及急性心肌缺血时迷走神经刺激对老年大鼠缺血性室性心律失常的影响.方法 结扎大鼠冠状动脉前降支制备急性心肌缺血模型,随机分为(1)成年组:假手术组(SO,n=10)、心肌缺血组(MI,n=15)、心肌缺血+迷走神经刺激组(MI-VNS,n=15)、心肌缺血+迷走神经刺激+阿托品(0.5 mg/kg)组(MI-VNS-Atr,n=13)和心肌缺血+迷走神经刺激+生胃酮(10 mg/kg)组(MI-VNS-CBX,n=11).(2)老年组:假手术组(SO,n=10)、心肌缺血组(MI,n=15)、心肌缺血+迷走神经刺激组(MI-VNS,n=15)、心肌缺血+迷走神经刺激+阿托品(0.5 mg/kg)组(M1-VNS-Atr,n=13)和心肌缺血+迷走神经刺激+生胃酮(10 mg/kg)组(MI-VNS-CBX,n=11).心电图监测室性心律失常的发生.Western blot分析Cx43蛋白表达变化.结果 结扎冠状动脉30 min内,老年MI组室性心动过速(室速)和心室颤动(室颤)发生率较成年MI组显著增加(P＜0.05);老年MI-VS组室速和室颤发生率与老年MI组相比差异无统计学意义(P＞0.05),但老年MI-VS组不可逆性室颤发生率较老年MI组明显减少(P＜0.05).冠状动脉结扎30 min后,缺血没有引起成年组和老年组的总Cx43含量改变(P＜0.05);但缺血引起成年组和老年组的非磷酸化Cx43含量明显增加,迷走神经刺激能够明显抑制成年组和老年组中缺血引起的Cx43脱磷酸化(P＜0.05);而阿托品和生胃酮明显阻断了迷走神经刺激抑制缺血引起的Cx43脱磷酸化的作用(P＜0.05).但实验发现老年SO组Cx43表达较成年SO组明显减少(P＜0.05).结论 老年大鼠缺血性室性心律失常发生率明显增加,而迷走神经刺激的抗缺血性室性心律失常的效应明显减弱,其机制可能与老年大鼠心室肌Cx43表达较成年大鼠明显减少有关.     

抑制NADPH氧化酶拮抗兔心力衰竭后室性心律失常

目的 探讨抑制还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶对心力衰竭后室性心律失常的影响及其机制.方法 家兔随机分为假手术安慰剂组、假手术NADPH氧化酶抑制剂(apocynin)组、心力衰竭安慰剂组、心力衰竭apocynin组.通过容量超负荷联合压力超负荷建立家兔心力衰竭模型.apocynin和安慰剂以15 mg/d口服.8周后,行超声心动图检查观察动物心脏结构和功能的变化.通过在体电生理研究分析兔左心室3层心肌单相动作电位复极90％的时限(MAPD90),观察室性心律失常诱发情况,检测心室颤动(室颤)阈值.运用比色法检测心肌超氧化物歧化酶(SOD)和丙二醛(MDA)水平.利用Western blot法检测心肌缝隙连接蛋白43(Cx43)的蛋白表达.结果 心力衰竭兔出现明显心脏扩大和心功能异常,3层心肌MAPD90延长[内层(179.8±5.8)ms对(137.0±4.5) ms;中层(180.6±8.6)ms对(137.3±4.8) ms;外层(175.0±11.3)ms对(136.3±3.9)ms;P＜0.05],室性心律失常诱发增多,室颤阈值显著降低(10.8±2.4)V对(21.0±2.8)V(P＜ 0.05),心肌SOD活力降低(91.0±10.1)U/mg protein对(160.3±14.2)U/mg protein(P＜0.05),MDA水平升高(3.0±0.3)nmol/mg protein 对(1.2±0.1)nmol/mg protein(P＜0.05),Cx43蛋白表达显著降低(0.5对0.9,P＜0.05),且以磷酸化Cx43降低为主(P＜0.05).apocynin干预可显著改善心力衰竭兔心脏功能,降低氧化应激水平[SOD(132.7±8.8)U/mg protein对(91.0±10.1)U/mg protein;MDA(1.9±0.2) nmol/mg protein对(3.0±0.3)nmol/mg protein(P＜0.05)],减少室性心律失常诱发,提高室颤阈值(17.4±1.6)V对(10.8±2.4)V(P＜0.05),增加Cx43蛋白表达(P＜0.05).结论 心力衰竭后氧化应激水平升高导致Cx43蛋白降低,是心力衰竭后室性心律失常发生的病理生理机制之一,抑制NADPH氧化酶可能是治疗心力衰竭后室性心律失常的方向之一.     

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.     

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.     

N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis： Randomized,placebo-controlled pilot study

AIM： To evaluate the effectiveness and safety of oral N-acetyl-L-cysteine （NAC） co-administration with mesalamine in ulcerative colitis （UC） patients.
METHODS： Thirty seven patients with mild to moderate UC were randomized to receive a four-wk course of oral mesalamine （2.4 g/d） plus N-acetyl-L-cysteine （0.8 g/d） （group A） or mesalamine plus placebo （group B）. Patients were monitored using the Modified Truelove-Witts Severity Index （MTWSI）. The primary endpoint was clinical remission （MTWSI ≤ 2） at 4 wk. Secondary endpoints were clinical response （defined as a reduction from baseline in the MTWSI of ≥ 2 points） and drug safety. The serum TNF-α, interleukin-6, interleukin-8 and MCP-1 were evaluated at baseline and at 4 wk of treatment. RESULTS： Analysis per-protocol criteria showed clinical remission rates of 63% and 50% after 4 wk treatment with mesalamine plus N-acetyl-L-cysteine （group A） and mesalamine plus placebo （group B） respectively （OR = 1.71; 95% CI： 0.46 to 6.36; P = 0.19; NNT = 7.7）. Analysis of variance （ANOVA） of data indicated a significant reduction of MTWSI in group A （P = 0.046） with respect to basal condition without significant changes in the group B （P = 0.735） during treatment. Clinical responses were 66% （group A） vs 44% （group B） after 4 wk of treatment （OR = 2.5; 95% CI： 0.64 to 9.65; P = 0.11; NNT = 4.5）. Clinical improvement in group A correlated with a decrease of IL-8 and MCP-1. Rates of adverse events did not differ significantly between both groups.
CONCLUSION： In group A （oral NAC combined with mesalamine） contrarily to group B （mesalamine alone）, the clinical improvement correlates with a decrease of chemokines such as MCP-1 and IL-8. NAC addition not produced any side effects.     

Delorme's transrectal excision for internal rectal prolapse

Surgical therapy of functional outlet obstruction in patients with internal rectal intussusception may include abdominal, perineal, or transrectal procedures. Because abdominal procedures often result in significant physiologic impact but unrelieved constipation, the authors have elected Delorme's transrectal excision for management of these patients. Since a short-term placebo effect attends many therapies, this report describes results of transrectal excision only after a threeyear postoperative period. Delorme's transrectal excision of internal intussusception accomplished sustained symptomatic relief in over 70 percent of otherwise refractory constipated patients. The association of internal intussusception with other abnormalities underscores the importance of defining both anatomic and functional components when selecting patients whose constipation may require surgical therapy. Critical technical elements, surgical pitfalls, and potential complications of the procedure are discussed.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Toronto, Canada, June 11 to 16, 1989.     

The oral glucose tolerance test: A comparison of the time points on the basis of limit values,normal dispersion,and reproducibility

Summary Time points in the glucose tolerance test (GTT) are compared on the basis of limit values, dispersion within a reference population, and reproducibility. We suggest using the distance between a limit value and the median reference value as a measure of the magnitude of abnormality. The distance between 140 mg/100 ml and the median fasting plasma glucose value is chosen as a standard distance and limits for other points in the GTT are calculated to equal this standard distance of abnormality. We suggest that the probability of correctly interpreting an inividual result is directly related to the reproducibility of the test and inversely related to the percentage of the total range of values which is dispersed among the normal population. The ratio of reproducibility to percentage normal dispersion is proposed as an index of the probability of correctly interpreting an individual result. According to this index, the probability of correct interpretation varies in order: fasting plasma glucose concentration>3-h>2-h>0.5-h>1-h plasma glucose concentration.