活血通脉灵对实验性心肌缺血大鼠心肌损伤的抗炎保护作用

目的:探讨以浊毒理论为指导的活血通脉灵对实验性心肌缺血大鼠心肌损伤的抗炎保护作用机制。方法:将肢体Ⅱ导联心电图正常的50只Wistar雄性大鼠随机分为5组,每组10只(空白组、模型组、消心痛组及活血通脉灵高、低剂量治疗组)。空白组以普通饲料喂养;其余各组以高脂饲料喂养,形成高脂血症模型,在此基础上,皮下注射异丙肾上腺素,形成心肌缺血的复合模型。空白组和模型组分别灌等体积的生理盐水,其余各组分别灌消心痛、活血通脉灵高、低剂量进行治疗。采用血清学方法、放射免疫法等研究方法来观察各组心肌酶、炎症因子的变化,比较各组的差别。结果:活血通脉灵高、低剂量均能显著降低血清中心肌酶的含量(P<0.01),且能降低血清中肿瘤坏死因子和白介素-6的水平(P<0.01)。结论:活血通脉灵对大鼠心肌缺血而引起的心肌损伤具有保护作用,可改善心肌供血,有一定抗炎作用。     

Heterogeneity in epithelium-dependent responses

The airway epithelium exerts a profound influence on the responsiveness of bronchial smooth muscle to both contracting and relaxing agents. This may be due to the release of an epithelium-derived factor or factors. There is a considerable heterogeneity in the effects of the epithelium between orders of bronchi, between species, and between pharmacologic agents. Such heterogeneity may reflect variations in the release and/or effect of the epithelium-derived relaxing factor(s). This report demonstrates that: (1) there is a basal and a stimulated release of the factor, (2) the prominence of different types of release varies between species, (3) the effect of the epithelium on relaxation of bronchial smooth muscle is greatest in the presence of high degrees of cholinergic tone, (4) the effects of the epithelium are not mediated via cyclic GMP, and (5) the epithelium-derived relaxing factor is not nitric oxide.     

心肌内向整流钾通道激动剂抑制异丙肾上腺素所致大鼠心室重构

目的:观察和探讨内向整流钾通道(Ⅰ_(K1))激动剂盐酸扎考必利(zacopride,Zac)对异丙肾上腺素(isoproterenol,Iso)所致心室重构的影响及作用机制。方法:SD大鼠随机分为正常对照组、Iso模型组、Zac干预组、Zac+氯喹干预组和卡托普利阳性对照组。腹腔注射异丙肾上腺素3 mg/kg,每天1次,连续给药10 d,观测各组全心质量/体质量比和左心室质量/体质量比。用全细胞膜片钳技术检测大鼠心室肌细胞电压门控钙电流(Ⅰ_(Ca-L))、静息膜电位(RMP)及动作电位时程(APD)的变化。选用新生1~3 d的SD乳鼠,用0.08%胰蛋白酶和0.04%Ⅱ型胶原酶消化心脏组织,经差速贴壁法和5-溴脱氧尿嘧啶核苷纯化心肌细胞后随机分成正常对照组、Iso模型组、Zac干预组、Zac+BaCl_2干预组和Zac+氯喹干预组,培养24 h后用激光共聚焦显微镜检测心肌细胞内游离钙离子浓度。结果:Iso模型组与正常对照组比较,全心肥厚指数、左心室肥厚指数明显增加,膜片钳结果提示RMP减小APD明显延长;Zac干预组明显抑制心肌肥大,并增大RMP,缩短APD。同时应用低剂量Ⅰ_(K1)抑制剂氯喹可明显抑制Zac的抗心室重构作用,并逆转Zac对RMP和APD影响。在乳鼠心肌细胞,Iso可使细胞表面积增大,细胞内[Ca~(2+)]_i增高;Zac干预后细胞形态恢复至正常或接近正常水平,并显著减轻钙超载。Ⅰ_(K1)阻断剂BaCl_2和氯喹可阻断Zac的效应。结论:Ⅰ_(K1)选择性激动剂Zac明显抑制异丙肾上腺素所致的心室重构,其机制可能为增强Ⅰ_(K1),进而增大RMP,缩短APD,从而阻断心肌细胞内钙超载依赖的信号通路。     

腺苷A1受体与к阿片肽受体激活对异丙肾上腺素诱导的心肌细胞肥大的交互作用

目的观察腺苷A1受体与κ阿片肽受体(κ-OR)激活对异丙肾上腺素(Iso)诱导的心肌细胞肥大的交互作用及机制。方法体外培养大鼠乳鼠心肌细胞,以Iso 10μmol/L诱导心肌细胞肥大,观察腺苷A1受体激动剂R(-)-N6-(2-phenylIsopropyl)adenosine(R-PIA)1μmol/L和κ-OR激动剂U50,488H1μmol/L对其作用,进一步探讨腺苷A1受体拮抗剂8-cyclopentyl-1,3-dipropylxanthine(CPDPX)0.1μmol/L存在时κ-OR的激活对细胞肥大的影响和κ-OR拮抗剂nor-binaltorphimine(NOR-BNI)1μmol/L存在时腺苷A1受体的激活对心肌细胞肥大的影响。通过Lowry法测心肌细胞蛋白含量;消化分离法及计算机图像分析系统测细胞体积;以Fluo-3/AM为荧光探针,共聚焦显微镜下测量心肌细胞内[Ca2+]i变化;RT-PCR法检测心肌细胞心房钠尿肽(ANP)的mRNA表达。结果 10μmol/LIso可以诱导心肌细胞肥大,1μmol/L的R-PIA(腺苷A1受体激动剂)可以明显抑制Iso诱导的心肌细胞蛋白合成增加、体积增大、ANPmRNA表达增加、心肌细胞内[Ca2+]i荧光强度增大,该抑制作用可以被1μmol/Lκ-OR拮抗剂NOR-BNI部分阻断;κ-OR激动剂U50,488H1μmol/L可以明显抑制Iso诱导的心肌细胞蛋白合成增加、体积增大、ANPmRNA表达增加、心肌细胞内[Ca2+]i荧光强度增大,该抑制作用可以被腺苷A1受体拮抗剂CPDPX部分阻断。结论腺苷可通过激动A1受体、阿片肽可通过激动κ受体抑制Iso诱导的心肌肥大,二者可以通过影响心肌细胞内[Ca2+]i浓度的增大而交互抑制Iso诱导的心肌肥大。     

Effect of isoproterenol and taurine on heart calcium in normal and cardiomyopathic hamsters

Calcium accumulation has been implicated in the cardiac necrosis induced by isoproterenol and in the development of the cardiomyopathy in the BIO 14.6 hamster. Taurine, a natural constituent of the heart, has been shown to exert a modulating effect on calcium levels in the heart. Heart calcium and taurine levels were determined in BIO 14.6 and random bred (F₁B) hamsters treated with isoproterenol (80 mg/kg) following a 60 day drinking regimen of either taurine (100 mmol/l) or guanidinoethyl sulfonate (1%). Taurine supplementation provided some protection for the random bred hamster heart against isoproterenol induced calcium accumulation, but that protection was not demonstrable in the BIO 14.6 strain despite an elevated heart taurine content. The feeding of guanidinoethyl sulfonate decreased the taurine content of the heart in both strains, but guanidinoethyl sulfonate was unable to block taurine elevation following isoproterenol treatment in either strain. Since taurine feeding retards the usual calcium accumulation in the BIO 14.6, but is without statistically significant effect on the additional calcium accumulation induced by isoproterenol, the protecitive action of taurine seems insufficient to counteract the combined effect of isoproterenol and the myopathic process.     

Increased cardiac myosin ATPase activity as a biochemical adaptation to running training: enhanced response to catecholamines and a role for myosin phosphorylation

The effects were studied of prior running training on protein phosphorylation and adenosine triphosphatase (ATPase) activities of natural actomyosin isolated from perfused rat hearts. Myosin Ca²⁺-ATPase activities were significantly higher in running-trained hearts than in controls, whereas the Ca²⁺-stimulated, Mg²⁺-dependent ATPase activities of natural actomyosin were not changed. After treatment of isolated perfused hearts with the β-agonist isoproterenol, both troponin-I and myosin P light chains became phosphorylated. Troponin-I phosphorylation (1 mol/mol) was the same in both sets of hearts and was accompanied by similar changes in cardiac cyclic AMP contents. The V_max values for myosin Ca²⁺-ATPase activity were increased after isoproterenol treatment in all the perfused hearts, but to a significantly greater extent in the hearts of running trained animals; this was correlated with enhancement of both the rate and extent of myosin P light chain phosphorylation. Enhanced Ca²⁺-dependent myosin P light chain phosphorylation, further enhanced by β-adrenergic stimulation, represents, at the molecular level, a biochemical response to running training.     

The effects of trimetoquinol on the intact rabbit heart and myocardial adenylate cyclase activity: evidence for spare myocardial beta receptors

We have compared and contrasted the actions of (-)isoproterenol and (+/-) trimetoquinol on rabbit heart preparations. In the presence of either GTP or Gpp[NH]p (guanosine-5'-(beta, gamma imino) triphosphate), trimetoquinol displayed partial agonist activity in stimulating adenylate cyclase activity in a particulate rabbit heart preparation. Trimetoquinol enhanced adenylate cyclase activity 20% or 65% of the maximum obtainable by isoproterenol in the presence of GTP or Gpp[NH]p respectively. In the presence of GTP, concentrations of catecholamines required to enhance cyclase activity 15% of the maximum obtainable with isoproterenol (EC15) were 2.0 X 10(-7) M and 5.5 X 10(-8) M for trimetoquinol and isoproterenol, respectively. In the presence of Gpp[NH]p EC30 values were 2.0 X 10(-7) and 3.5 X 10(-8) M for trimetoquinol and isoproterenol respectively. Trimetoquinol also displayed partial agonist activity for the ability to increase cAMP levels in the isolated perfused rabbit heart. By contrast trimetoquinol was equieffective to isoproterenol at increasing tension development and rate of contraction of the isolated perfused heart. Concentrations of catecholamines required to increase tension and rate of contraction 50% of the maximum obtainable with isoproterenol were 1.5 X 10(-7) M and 1.7 X 10(-8) M for trimetoquinol and isoproterenol, respectively. These data show that only a partial stimulation of adenylate cyclase activity and cAMP levels by trimetoquinol is sufficient to produce maximal changes in mechanical activity of the heart.(ABSTRACT TRUNCATED AT 250 WORDS)     

大鼠急性心肌损伤E选择素和细胞因子的变化

目的观察异丙肾上腺素导致大鼠急性心肌损伤早期E选择素和细胞因子TNF-α、IL-1βmRNA的变化,进一步探讨E选择素和细胞因子TNF-α、IL-1β在异丙肾上腺素导致大鼠急性心肌损伤发生发展中的作用。方法将大鼠随机分为对照组(35只)和实验组(35只),实验组给予异丙肾上腺素(isoproterenol,Iso),对照组给予生理盐水,分别在给药后4、8、16、24、48h各取7只大鼠心脏,光镜下观察心肌形态结构病理改变,应用逆转录-聚合酶链反应(RT-PCR)检测心肌组织E选择素、TNF-α和IL-1βmRNA的表达。结果实验组4hE选择素mRNA表达与对照组比较差异无统计学意义(P>0.05),实验组E选择素mRNA表达8h开始升高,24h达高峰,48h恢复正常;实验组TNF-αmRNA表达4h已经升高,16h达高峰,24h到48h逐渐下降;实验组IL-1βmRNA表达4h已经升高,8h达高峰,16h到48h逐渐下降。结论E选择素和细胞因子TNF-α、IL-1β在大鼠急性心肌损伤的发生中具有重要意义。     

The Effect of Hypertension,Sodium, and Race on Isoproterenol Sensitivity

ABSTRACT

The heart rate response to isoproterenol is felt to be an index of beta receptor sensitivity. We studied this response in 55 normotensive and mildly hypertensive men on two dietary salt intakes (10 meq sodium per day, and 200 meq sodium per day). There was no relationship between receptor functioning and diagnosis of hypertension. Similarly, age, relative body weight, and resting plasma catecholamines were unrelated to the heart rate response to isoproterenol.

There was however, a significant three-way interaction between race, diagnosis, and dietary salt. Black hypertensives fail to down regulate their beta receptors' response to isoproterenol in the face of a high salt challenge (p<.006).     

2-[对-(二甲氨基)苯乙烯]氯化甲基吡啶对大鼠心电图、豚鼠左心房收缩及乳头肌动作电位的影响

2-[对-(二甲氨基)苯乙烯]氯化甲基吡啶(DSPM-Cl),是由氯取代2-[对-(二甲氨基)苯乙烯]碘化甲基吡啶(DSPM)上的碘而得。本文应用心电图、机械收缩描记方法及细胞内标准微电极技术,研究DSPM-Cl对大鼠心电图(ECG)、豚鼠心房肌量效曲线及对豚鼠乳头肌快反应动作电位(AP)、高钾除极慢反应动作电位(SAP)的影响。结果显示,DSPM-Cl(2mg·kg^-1)对大鼠有明显的负性频率、负性传导作用,分别使PP间期、PR间期延长达66.2%(P<0.01),17.0%(P<0.01),50μmol·L^-1能明显抑制左心房收缩力,非竟争性拮抗Iso及CaCl₂对豚鼠左心房的正性肌力作用,PD^2'分别为4.6,4.34,100μmol·L^-1DSPM-Cl延长动作电位时程APD₉₀,有效不应期(ERP),降低高钾除极豚鼠乳头肌0期最大上升速率Vmax,其作用与Ver相似,提示DSPM-Cl可能为钙拮抗剂。