Cardioprotective effects of sinomenine in myocardial ischemia/reperfusion injury in a rat model

BackgroundIschemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat.MethodsRat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed.ResultsPre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators.ConclusionOur result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction.     

The roles of prostaglandin E2 and D2 in lipopolysaccharide-mediated changes in sleep

When living organisms become sick as a result of a bacterial infection, a suite of brain-mediated responses occur, including fever, anorexia and sleepiness. Systemic administration of lipopolysaccharide (LPS), a common constituent of bacterial cell walls, increases body temperature and non-rapid eye movement (NREM) sleep in animals and induces the production of pro-inflammatory prostaglandins (PGs). PGE₂ is the principal mediator of fever, and both PGE₂ and PGD₂ regulate sleep–wake behavior. The extent to which PGE₂ and PGD₂ are involved in the effect of LPS on NREM sleep remains to be clarified. Therefore, we examined LPS-induced changes in body temperature and NREM sleep in mice with nervous system-specific knockouts (KO) for the PGE₂ receptors type EP₃ or EP₄, in mice with total body KO of microsomal PGE synthase-1 or the PGD₂ receptor type DP, and in mice treated with the cyclooxygenase (COX) inhibitor meloxicam. We observed that LPS-induced NREM sleep was slightly attenuated in mice lacking EP₄ receptors in the nervous system, but was not affected in any of the other KO mice or in mice pretreated with the COX inhibitor. These results suggest that the effect of LPS on NREM sleep is partially dependent on PGs and is likely mediated mainly by other pro-inflammatory substances. In addition, our data show that the main effect of LPS on body temperature is hypothermia in the absence of nervous system EP₃ receptors or in the presence of a COX inhibitor.     

高位硬膜外阻滞对猪急性心肌缺血/再灌注损伤时血浆TXB2和6-keto-PGF1α水平的影响

目的探讨0.5%布比卡因高位硬膜外阻滞对急性心肌缺血/再灌注损伤时血栓素B2(TXB2)和6-酮-前列腺素F1α(6-keto-PGF1α)的影响.方法健康雄性家猪20只,体重(23.0±2.5)kg,随机分为布比卡因组(Ⅰ组)、生理盐水组(Ⅱ组).静注10mg.kg-1硫喷妥钠后,气管插管,静点琥珀胆碱和芬太尼控制呼吸,维持麻醉.T3～4穿刺置入硬膜外导管,按分组分别硬膜外注射0.5%布比卡因和生理盐水各2ml,15min后结扎左冠脉前降支40min.分别在给药前和结扎40min时、开放后1h、3h、5h抽取右心房血,测定血浆TXB2、6-keto-PGF1α的浓度.给药前所测定的心率(HR)、平均动脉压(MAP)、中心静脉压(CVP)作为基础值.结果Ⅱ组各时点血液动力学无明显变化,Ⅰ组HR、MAP和CVP分别下降22%、25%和28%.两组再灌注后1h、3h及5h TXB2、TXB2/6-keto-PGF1α比值逐渐升高,且均显著高于给药前和结扎40min.Ⅰ组升高程度显著低于Ⅱ组(P＜0.05).而6-keto-PGF1α组内组间比较,变化趋势与TXB2恰相反.Ⅰ组有1只因室颤而死亡,Ⅱ组有4只(P＜0.05).结论心肌缺血/再灌注损伤与TXB2和6-keto-PGF1α有一定关系,高位硬膜外阻滞通过调节缺血/再灌注后血栓素A2和前列环素的平衡在一定程度上减轻了心肌缺血/再灌注损伤.     

流行性出血热若干体液因子和肾脏血液动力学的变化

对28例流行性出血热（EHF）患者作了体液因子和肾脏血液动力学的观察研究。发现患者从发热期至多尿初期血浆内皮素（ET）、血栓素B2（TXB2）、血管紧张素-Ⅱ（AT－Ⅱ）均高于正常，P物质（SP）则低于正常，6-酮前列腺素F1α（6-k-PGF1α）除极期外其它各期亦见减低，肾小球滤过率（GFR）与肾有效血浆流量（ERPF）从发热后期至多尿期均显著下降，至恢复初期多数重型患者仍未达到正常。上述结果提示体液因子的失衡是造成内脏缺血和急性肾衰的重要因素。     

短暂性脑缺血发作患者血浆中TXB2和PGF1α含量检测

本文用放射免疫法测定47例短暂性脑缺血发作(TIA)患者血浆中血栓素B_2(TXB_2)和6酮-前列腺F_(1α)(PGF_(1α))的含量。结果发现TIA患者血浆中TXB_2含量增高,PGF_(1α)降低;头颅CT或MRI示有小灶性梗塞者及TIA发作持续时间长于30min者TXB_2升高和PGF_(1α)降低更显著。治疗3个月后,血浆PGF_(1α)显著增高。TXB_2和PGF_(1α)在体内的失平衡是急性脑血管疾病发病的重要机理之一。     

川芎嗪对脑外伤患者血栓素、前列腺环素及颅内压的影响

28例重度脑外伤患者分为川药嗪治疗组和一般治疗对照组,两组病人均于用药前和用药后3小时测定血浆和脑室内脑脊液(VCSF)中血栓素代谢产物(TXB_2)前列腺环素代谢产物6—酮—PGF_(la)(6KP)和颅内压。结果表明:两组治疗前血浆、VCSF中TXB_2及T/K均明显高于正常献血员对照组,川芎嗪能降低脑外伤患者血浆、VCSF中TXB_2及T/K值,对颅内压则无明显影响。提示川芎嗪能抑制脑外伤对血小板的激活、纠正循环血中TXA_2—PGI_2平衡失调,从而改善脑微循环。     

肠溶阿斯匹林剂量和血阿斯匹林及水杨酸盐浓度与药效关系探讨

本文探讨了ＡＳＡ剂量与药效的关系及血ＡＳＡ、ＳＡ药物浓度监测的临床意义，结果表明：（１）ＡＳＡ剂量与６－ｋｅｔｏ－ＰＧＦ_（１α）抑制率呈正相关（Ｐ＜０．０１），而与ＴＸＢ_２及ＰＡｇＲ抑制率无相关性（Ｐ＞０．１）；（２）本文采用ＨＰＬＣ内标法同时测定血ＡＳＡ和ＳＡ浓度，结果准确，方法简便；（３）当口服小剂量ＡＳＡ防治ＣＩ时，监测血ＡＳＡ和ＳＡ以调整ＡＳＡ用药剂量的临床价值并非十分重要。     

失血性休克状态下肢体缺血再灌注影响休克发展的研究

目的：研究失血性休克状态下骨骼肌缺血再灌注对休克发展的影响。方法：雌性家兔１２只，随机等分为休克对照组（Ⅰ组）和休克伴双后肢缺血再灌注组（Ⅱ组）。戊巴比妥钠麻醉，气管切开，自主呼吸，并全身肝素化。经左颈外静脉，按１ｍｌ·ｋｇ－１·ｍｉｎ－１的速度放血５分钟，停５分钟，以左颈总动脉ＭＡＰ达４．０±０．２ｋＰａ为休克开始，此时Ⅱ组阻断腹主动脉末端，９０分钟后松开。结果：休克后１２０分钟，血中ＴＸＢ２、ＴＸＢ２／６－ｋｅｔｏ－ＰＧＦ１α、乳酸、酸性磷酸酶及Ｍｇ２＋，Ⅱ组均显著高于Ⅰ组，而休克９０分钟时，各值两组间无显著性差异。结论：失血性休克状态下肢体骨骼肌缺血再灌注可能对休克的发展产生不利影响。     

糖尿病中促动脉粥样硬化因素的探讨

我们对64例糖尿病患者和20名正常人的糖代谢、脂代谢、血小板和血管内皮细胞前列腺素代谢的水平进行了临床观察。发现糖尿病患者载脂蛋白B、低密度脂蛋白胆固醇、总脂固醇、甘油三酯和血栓素B_2的浓度均有不同程度的升高,而载脂蛋白A_1、高密度脂蛋白胆固醇和6-酮前列腺素F_(1α)的浓度则下降。同时糖代谢异常与脂代谢紊乱、糖代谢异常与前列腺素代谢物水平、以及脂代谢紊乱与前列腺素代谢物水平之间均无明显关系。推想糖尿病中促动脉粥样硬化的各种高危因素可能从不同的角度作用于血管壁,促进动脉粥样硬化的发生和发展。