清热解毒中药干预大鼠急性心肌缺血损伤的实验研究

目的：研究清热解毒中药干预大鼠急性心肌缺血损伤的药效学,探讨其治疗冠心痛心肌缺血的作用机制。方法：复制大鼠急性心肌缺血模型,以肌酸激酶（CK）、乳酸盐脱氢酶（LDH）、肿瘤坏死因子-α（TNF-α）、白介素-6（IL-6）、一氧化氮（NO）、一氧化氮合成酶（NOS）、超氧化物歧化酶（SOD）、丙二醛（MDA）为观测指标,以地尔硫卓为平行对照,观察清热解毒中药干预冠心病心肌缺血的作用机制。结果：清热解毒中药能显著降低模型大鼠血清中CK、LDH活性、MDA含量、TNF-α与IL-6水平及显著升高模型大鼠血清中SOD活力、NO与NOS水平（P〈0．05,P〈0．01）。结论：清热解毒中药能够保护缺血心肌。     

硫化氢对急性心肌缺血大鼠心肌线粒体损伤的影响

目的：探讨硫化氢（H2S）对急性心肌缺血大鼠线粒体功能的影响,并探讨其改善急性心肌缺血损伤的作用机制。方法：通过结扎大鼠左冠状动脉前降支建立急性心肌缺血模型。雄性SD大鼠48只随机分为6组（n=8）：假手术组,缺血组,缺血＋硫氢化钠（NaHS）低、中、高剂量组和缺血＋炔丙基甘氨酸（PPG）组。透射电镜观察心肌组织线粒体超微结构;检测血浆中H2S含量、心肌组织CSE活性;测定心肌线粒体活力、膜肿胀度及线粒体总ATP酶、谷胱甘肽过氧化物酶（GSH-PX）、超氧化物歧化酶（SOD）的活性和丙二醛（MDA）含量。结果：与假手术组比较,缺血组大鼠血浆H2S含量和心肌组织中CSE活性降低;心肌线粒体膜肿胀,线粒体活力下降;线粒体中MDA含量明显升高,ATP酶、SOD、GSH-Px活性明显降低（P〈0.01）。与缺血组比较,缺血＋NaHS低、中、高剂量组大鼠血浆H2S含量和心组织中CSE活性均升高;缺血＋NaHS中、高剂量组大鼠心肌线粒体MDA含量明显减少,膜肿胀度减轻;缺血＋NaHS低、中、高剂量组线粒体活力有所恢复,ATP酶、SOD、GSH-Px的活性明显升高（P〈0.05或P〈0.01）。PPG可部分减弱H2S的心肌保护作用（P〈0.05或P〈0.01）。结论：H2S可增强线粒体ATP酶、SOD、GSH-Px的活性,降低线粒体脂质过氧化水平,从而起到对大鼠急性心肌缺血的保护作用。     

内皮素-1 mRNA反义寡核苷酸预防大鼠急性缺血性心律失常

本实验夹闭雄性ＳＤ大鼠冠状动脉左前降支（ＬＡＤ）造成急性心肌缺血,观察ＬＡＤ闭塞后１ｈ内缺血性心律失常的发生。在ＬＡＤ夹闭前２ｈ,静脉注射本室设计的人内皮素－１ｍＲＮＡ反义寡核苷酸（ＡＳ－ＯＤＮ）以阻断ＥＴ－１ｍＲＮＡ表达,观察ＡＳ－ＯＤＮ对血浆ＥＴ－１浓度和急性缺血性心律失常的影响。     

Protective roles of cornuside in acute myocardial ischemia and reperfusion injury in rats

Cornuside is a secoiridoid glucoside isolated from the fruit of Cornus officinalis SIEB. et ZUCC. In this study, we investigated the anti-myocardial ischemia and reperfusion (I/R) injury effects of cornuside in vivo and elucidated the potential mechanism. Rat models of myocardial I/R were induced by coronary occlusion followed by reperfusion or by Isoproterenol (ISO), treatment of rats with cornuside (20 and 40 mg/kg, i.v.) protected the animals from myocardial I/R injury as indicated by a decrease in infarct volume, improvement in hemodynamics and reduction of myocardial damage severity. Treatment with cornuside also attenuated polymorphonuclear leukocytes (PMNs) infiltration, decreased myeloperoxidase (MPO) activity in the heart, lowered serum levels of pro-inflammatory factors and reduced phosphorylated IκB-α and nuclear factor kappa B (NF-κB) levels in the heart. Additionally, cornuside was shown to have remarkable antioxidant activity and inhibited ISO-induced myocardial cell necrosis. Thus, cornuside appeared to protect the rat from myocardial I/R injury by acting as an anti-inflammatory agent. These findings suggested that cornuside may be used therapeutically in the setting of myocardial I/R where inflammation and oxidant injury are prominent.     

诺迪康对急性心肌缺血和心衰大鼠血流动力学的影响

目的：研究诺迪康（rhodiola）对急性心肌缺血和心力衰竭大鼠血流动力学的影响,探讨该药的血流动力学作用机制。方法：采用垂体后叶素（Pit）诱发大鼠急性心肌缺血,20min后用戊巴比妥钠（PS）致急性心力衰竭,经Powerlab／4SP和BL-420E多道生物信号分析系统监测血流动力学。结果：①Rhodiola明显对抗Pit诱导的急性心肌缺血大鼠心电图ST段的偏移、HR的降低厦LVEDP的升高;＋dP／dtmax．dP／dtmax均高于NS组．该作用具有剂量依赖性。②和对照组相比,rhodiola能通过改善血流动力学对抗PS导致的急性心衰。结论：rhodiola能改善心肌缺血和心力衰竭大鼠的血流动力学。     

雌激素对去卵巢大鼠离体心脏缺血／再灌注损伤的保护作用

目的：探讨雌激素对去卵巢大鼠离体心脏缺血／再灌注损伤的保护作用。方法：成年SD雌鼠,随机分为假手术组（Sham）,双侧卵巢切除组（Ovx）和双侧卵巢切除后补充17β-雌二醇组（Ovx＋E2）。各组离体心脏再随机分为不同时间的缺血再灌注亚组。测量的指标包括冠脉流出液中LDH及CK含量、心室肌细胞存活率及产率、基础状态和异丙肾上腺素（ISO）刺激状态下收缩幅度。结果：30min缺血及其各复灌纽均显著增加冠脉流出液中LDH、CK的释放量。Ovx组LDH、CK漏出在30min缺血及再灌注条件下,显著高于正常灌注组,而Ovx＋E2组可减轻心肌损伤,减少LDH、CK的释放。10min和20min缺血对心肌细胞存活率、产率及冠脉流出液中LDH、CK含量影响均不明显。Sham、Ovx、Ovx＋E2各组心肌细胞基础收缩幅度在正常和10minⅠ＋30minR灌注条件下无显著差异。Ovx显著增加其他各组心肌细胞基础收缩和ISO刺激收缩幅度,Ovx＋E2可使其降至Sham水平。结论：雌激素对去卵巢大鼠心肌缺血／再灌注损伤具有保护作用。     

缺血后处理对缺血／再灌注大鼠心肌间质保护效应机制的探讨

目的：观察缺血后处理（IPIC）对缺血／再灌注（I／R）大鼠心肌基质金属蛋白酶-2（MMP-2）和基质金属蛋白酶抑制剂-2（TIMP-2）变化的影响,探讨IPTC保护I／R心脏间质的机制。方法：24只健康雄性SD大鼠随机分为3组（n：8）：假手术组（SC组）、I／R组和IPTC组。记录各组左室血流动力学变化,观察心肌胶原含量,测定血浆中肌酸激酶（CK）和乳酸脱氢酶（LDH）浓度。以Westernblot法测定心肌组织中MMP-2和TIMP-2蛋白表达水平,以实时定量PCR（RT-PCR）法检测MMP-2和TIMP-2的表达水平。结果：与sC组相比,I／R组心肌胶原含量和左室舒缩功能明显降低,血浆cK、LDH活力和心肌MMP-2蛋白表达及mRNA水平明显升高,TIMP-2蛋白及mRNA水平明显降低;而IPTC组,大鼠心肌胶原含量和左室舒缩功能明显升高,血浆cK、LDH活力和心肌MMP-2蛋白表达及mRNA水平降低,TIMP-2蛋白及mRNA水平升高。结论：IPTC对再灌注损伤心肌间质有保护作用,其机制可能与抑制心肌中MMP-2表达,促进TIMP-2表达有关。     

Protective effect of docosahexaenoic acid against brain injury in ischemic rats

Evidence suggests that inactivation of cell-damaging mechanisms and/or activation of cell-survival mechanisms may provide effective preventive or therapeutic interventions to reduce cerebral ischemia/reperfusion (I/R) injuries. Docosahexaenoic acid (DHA) is an essential polyunsaturated fatty acid in the central nervous system that has been shown to possess neuroprotective effects. We examined whether different preadministrative protocols of DHA have effects on brain injury after focal cerebral I/R and investigated the potential neuroactive mechanisms involved. Sprague–Dawley rats were intraperitoneally pretreated with DHA once 1 h or 3 days being subjected to focal cerebral I/R or daily for 6 weeks before being subjected to focal cerebral I/R. Reduction of brain infarction was found in all three DHA-pretreated groups. The beneficial effect of DHA on the treatment groups was accompanied by decreases in blood–brain barrier disruption, brain edema, malondialdehyde (MDA) production, inflammatory cell infiltration, interleukin-6 (IL-6) expression and caspase-3 activity. Elevation of antioxidative capacity, as evidenced by decreased MDA level and increased superoxide dismutase activity and glutathione level, was detected only in the chronic daily-administration group. The two single-administration groups showed increased phosphorylation of extracellular-signal-regulated kinase (ERK). Elevation of Bcl-2 expression was detected in the chronic daily-administration and 3-day-administration groups. In vitro study demonstrated that DHA attenuated IL-6 production from stimulated glial cells involving nuclear factor κB inactivation. Therefore, the data suggest that the neuroprotective mechanisms of DHA pretreatment are, in part, mediated by attenuating damaging mechanisms through reduction of cytotoxic factor production and by strengthening survival mechanisms through ERK-mediated and/or Bcl-2-mediated prosurvival cascade.     

缺血预处理对缺血/再灌注离体心脏的保护作用

目的：探讨连续多次短暂缺血预处理对缺血/再灌注损伤心肌的保护作用及机制。方法：采用大鼠离体心脏Lan-gendorff灌流模型,观察缺血预处理对心肌缺血/再灌注后不同时间点冠脉流出液中AST、CPK、UDH及冠脉流量,心肌组织中SOD、LPO以及再灌注性心律失常的影响。结果：缺血预处理可以减少缺血/再灌注损伤的心肌冠脉流出液中AST、CPK、LDH的含量,提高心肌SOD活性,降低LPO水平,并且抑制再灌注性心律失常的发生,提高再灌注期间的冠脉流量。结论：缺血预处理对心肌缺血/再灌注损伤具有一定保护作用。