参麦注射液对心肌缺血再灌注损伤大鼠钙调神经磷酸酶活性的影响

目的探讨参麦注射液(SMI)对大鼠心肌缺血再灌注损伤(MIRI)中钙调神经磷酸酶(CaN)活性变化的影响。方法 30只大鼠随机分为假手术组、模型组和SMI组各10只,检测各组心肌CaN变化,并测定其心肌组织超氧化物歧化酶(SOD)、丙二醛(MDA)、腺苷三磷酸(ATP)、CaN活性。结果与假手术组比较,模型组CaN活性、心肌细胞凋亡率、MDA含量明显升高(P<0.01),SOD含量、Na+-K+-ATP酶、Ca2+-Mg2+-ATP酶活性明显下降(P<0.01);与模型组比较,SMI组CaN活性、心肌细胞凋亡率、MDA含量明显下降(P<0.05),SOD含量、Na+-K+-ATP酶、Ca2+-Mg2+-ATP酶活性明显升高(P<0.05)。结论 SMI能够抑制大鼠心肌细胞CaN活性,对缺血再灌注心肌有一定保护作用。     

辛伐他汀联合杞菊地黄丸对糖尿病大鼠心脏的保护作用

目的 研究辛伐他汀和杞菊地黄丸对糖尿病大鼠心脏的保护作用.方法 将SD大鼠随机分为正常组、模型组、辛伐他汀组、杞菊地黄丸组、辛伐他汀与杞菊地黄丸联合治疗组.大鼠腹腔注射链脲佐菌素(STZ)诱导糖尿病模型.给药2 w后检测血糖、LDH、CK、Na+-K+-ATP酶、Ca2+-Mg2+-ATP酶、羰基、MDA、SOD、GSH-Px.结果 与模型组相比,联合治疗组大鼠血糖、LDH、CK水平明显降低,Na+-K+-ATP酶、Ca2+-Mg2+-ATP酶活性明显提高,羰基、MDA含量显著减少,SOD、GSH-Px活性显著上调,且效果明显优于单一用药组.结论 辛伐他汀联合杞菊地黄丸可减轻糖尿病大鼠心脏损伤,可能与其缓解氧化应激有关.     

大鼠心肌缺血再灌注损伤对心肌细胞膜Na~+-K~+-ATP酶亚基基因表达的影响与意义

目的 观察心肌缺血再灌注损伤大鼠心肌组织内洋地黄素水平、ATP酶活性、线粒体Ca2 浓度以及Na -K -ATP酶各亚基基因表达的改变,探讨内洋地黄素在心肌缺血再灌注损伤细胞内钙超载中的可能作用及其机制.方法 32只雄性SD大鼠随机分成假手术组,心肌缺血再灌注组,生理盐水组,维拉帕米组4组,每组8只.取缺血区左心室心肌检测心肌匀浆内洋地黄素水平、心肌细胞膜Na -K -ATP酶和Ca2 -Mg2 -ATP酶活性、线粒体Ca2 浓度;分别采用RT-PCR及Western bloting方法检测心肌Na -K -ATP酶α1、α2、α3和β1亚基mRNA及蛋白水平基因表达的改变.结果 心肌缺血再灌注时,心肌组织内洋地黄素水平明显升高,心肌细胞膜Na -K -ATP酶和Ca2 -Mg2 -ATP酶活性显著下降,线粒体Ca2 浓度升高,Na -K -ATP酶α1、α2、α3和β1亚基mRNA及蛋白水平基因表达均明显下降;维拉帕米预处理除显示降低线粒体Ca2 浓度外,对其它各项指标无明显影响.结论 心肌缺血再灌注能促进心肌内洋地黄素分泌增加,后者可能通过影响心肌细胞膜上的Na -K -ATP酶α1、α2、α3和β1亚基基因表达,抑制Na -K -ATP酶活性,导致线粒体内Ca2 超载,从而介导心肌缺血再灌注损伤.确切的作用机制有待于更深入研究.     

地精子皂甙抗缺血再灌性心律失常的作用机制研究

目的研究地精子皂甙对心律失常的作用机制.方法借助缺血-再灌注诱发心律失常大鼠模型,观察地精子皂甙对心律失常大鼠心肌组织乳酸代谢、Ca2 浓度、脂质过氧化损伤及心肌细胞膜Na -K -ATPase和Ca2 -Mg2 -ATPase活性的影响.结果心律失常大鼠心肌组织乳酸大量堆积,脂质过氧化增强,Ca2 含量增高,而心肌细胞膜Na -K -ATPase、Ca2 -Mg2 -ATPase活性明显降低;与模型组比较,地精子皂甙大、中剂量治疗组心肌组织乳酸含量明显降低,心肌组织丙二醛(MDA)含量也明显较低,而超氧歧化酶(SOD)活性升高(P＜0.05),其中地精子皂甙大、中剂量和维拉帕米皆可明显提高心肌细胞膜Na -K -ATPase、Ca2 -Mg2 -ATPase活性,并能明显降低心肌组织Ca2 含量(P＜0.05).结论地精子皂甙具有明显抗心律失常的作用,其作用机制是通过改善缺血再灌注心肌乳酸代谢,对抗脂质过氧化损伤,提高缺血心肌细胞ATP含量,提高心肌细胞膜Na -K -ATPase、Ca2 -Mg2 -ATPase活性,抑制了Ca2 超负荷,从而发挥其抗心律失常的作用.     

二氮嗪对大鼠缺血再灌注损伤脑组织线粒体ATP酶活性的影响

目的 探讨线粒体ATP敏感性钾通道开放剂二氮嗪对大鼠局灶性脑缺血再灌注损伤脑组织线粒体ATP酶活性的影响.方法 采用改良线栓法建立大鼠局灶性大脑中动脉缺血再灌注损伤模型.将21只Wistar雄性大鼠随机分为假手术组(N组)、缺血再灌注组(IR组)、二氮嗪干预组(DZ组).缺血1 h再灌注24 h后留取标本,测定脑组织线粒体Na+-K+-ATP酶、Ca2+-Mg2+-ATP酶活性的变化.结果 与假手术组比较,缺血再灌注组Na+-K+-ATPase、Ca2+-Mg2+-ATP酶活性明显降低(P<0.05);二氮嗪干预组Na+-K+-ATP酶、Ca2+-Mg2+-ATP酶活性均较缺血再灌注组有不同程度的提高(P<0.05).结论 二氮嗪预处理能通过提高脑组织线粒体Na+-K+-ATP酶、Ca2+-Mg2+-ATP酶活性,减轻脑缺血再灌注损伤,保护神经元线粒体的功能,有效维持大脑能量代谢,发挥脑保护作用.     

竹节参总皂苷对大鼠心肌缺血/再灌注损伤的保护作用

目的探讨竹节参总皂苷(t PJS)对大鼠心肌缺血再灌注损伤(MIRI)的保护作用及其机制。方法 SD大鼠40只,随机分为4组(n=10):对照组、MIRI组及t PJS低、高剂量组,采用结扎大鼠左冠状动脉前降支建立急性MIRI模型,观察急性MIRI状态下血流动力学的变化;测定心肌组织中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)和细胞能源Na+,K+-ATP及Ca2+-ATP酶活性,乳酸脱氢酶(LDH)、肌酸激酶(CK)及丙二醛(MDA)的含量的变化。结果与对照组比较,MIRI组心脏舒缩功能减退,SOD、CAT、GSH-Px、Na+,K+-ATP及Ca2+-ATP酶活性明显降低,乳酸脱氢酶(LDH)、肌酸激酶(CK)大量释放,MDA含量增高(P<0.01)。与MIRI组比较,t PJS低、高剂量组能不同程度的恢复左心室收缩压(LVSP)、心室内压最大变化速率(±dp/dtmax),降低左室舒张末期压(LVEDP),增强SOD、CAT、GSH-Px、Na+,K+-ATP及Ca2+-ATP酶活性,抑制MDA、LDH、CK升高(P<0.01,P<0.05)。结论 t PJS对MIRI具有明显的保护作用。     

黄龙通络胶囊对大鼠心肌缺血再灌注心律失常的影响

目的探索黄龙通络胶囊对心肌缺血再灌注所致大鼠心律失常模型的保护作用。方法采用结扎大鼠冠状动脉前降支,引起心肌缺血再灌注所致心律失常模型,记录各组大鼠Ⅱ导联心电图,并测定心肌组织中Na+-K+-ATPase、Ca2+-Mg2+-ATPase的活性。结果黄龙通络胶囊有稳定QRS间期、PR间期的作用,能降低抬高的ST段;能显著提高线粒体膜Na+-K+-ATPase、Ca2+-Mg2+-ATPase活性。结论黄龙通络胶囊可能是通过保持缺血-再灌注心肌细胞膜的稳定性,改善缺血心肌能量代谢障碍,而发挥其抗心律失常的作用。     

17-甲氧基-7-羟基-苯并呋喃查尔酮对大鼠心肌缺血再灌注损伤的保护作用

目的观察17-甲氧基-7-羟基-苯并呋喃查尔酮(YLSC)对心肌缺血再灌注(I/R)大鼠的影响。方法 SD大鼠60只随机分为6组,每组10只:假手术组,模型组,溶媒组,阳性药地尔硫卓组,YLSC低剂量组(2.50 mg/kg)、YLSC高剂量组(5.00 mg/kg)。缺血30 min再灌注60 min复制大鼠I/R模型。观察大鼠血流动力学指标HR,MAP,LVEDP和±dp/dtmax的变化,测定心肌组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、Na+-K+-ATP酶(Na+-K+-ATPase)、Ca2+-ATP酶(Ca2+-ATPase)的含量。结果与模型组比较,YLSC能剂量依赖性地降低HR、MAP和±dp/dtmax,升高LVEDP(P<0.05或P<0.01);YLSC还能剂量依赖性地减少MDA的释放,增加SOD、Na+-K+-ATPase和Ca2+-ATPase的活性(P<0.05或P<0.01)。结论 YLSC能改善I/R大鼠的心功能,机制可能与抗氧化、保护Na+-K+-ATPase和Ca2+-ATPase活性有关。     

茶皂苷减轻心肌缺血再灌注损伤的实验研究

目的观察茶皂苷对心肌缺血再灌注(MIR)损伤的保护作用并探讨其机制,为茶皂苷防治心肌缺血再灌注损伤提供科学的依据。方法采用左冠状动脉前降支结扎30min,复灌45min建立在体大鼠MIR模型。SD大鼠随机分成6组:假手术组,模型组,生理盐水组,维拉帕米组,小剂量、大剂量茶皂苷组。连续纪录Ⅱ导联心电图,于再灌注后取心尖部缺血区心肌,检测心肌细胞膜Na -K -ATP酶、Ca2 -ATP酶活性和线粒体内Ca2 含量。结果MIR损伤时,心肌细胞膜Na -K -ATP酶、Ca2 -ATP酶活性显著下降,线粒体内Ca2 含量升高;心电图ST段显著抬高,并发生明显的室性心律失常。茶皂苷可明显对抗上述变化。结论茶皂苷可通过减轻细胞内钙超载对MIR损伤起保护作用。     

肾性高血压大鼠心肌Na+-K+-ATP酶和钙调神经磷酸酶mRNA表达及厄贝沙坦的干预作用

目的观察肾性高血压大鼠(RHR)左心室肌组织Na+-K+-ATP和钙调神经磷酸酶(CaN)mRNA的表达及其活性以及厄贝沙坦干预。方法采用两肾一夹制造肾性高血压模型,造模成功大鼠随机分为模型组和厄贝沙坦组(50 mg.kg-1.d-1),每组7只;另设假手术组大鼠7只;测量各组大鼠术前、术后血压,用药8 w后,测量大鼠左心室质量指数(LVM I),采用实时荧光定量PCR技术检测左心室肌组织(LV)Na+-K+-ATP酶α1亚单位mRNA、CaN mRNA及心钠素(ANP)mRNA表达,生化酶学方法检测心肌Na+-K+-ATP酶、CaN活性。结果与假手术组比较,RHR血压、LVM I及心肌ANP mRNA表达明显增加,心肌Na+-K+-ATP酶α1亚单位mRNA表达及其活性明显降低,CaN mRNA表达及其活性升高;与RHR模型组比较,厄贝沙坦能降低RHR血压、LVM I及心肌ANP mRNA表达,上调Na+-K+-ATP酶α1亚单位mRNA表达(P<0.05)并增加其活性,降低CaN mRNA表达(P<0.05)及CaN活性。结论 RHR左心室肥厚发生及逆转与心肌Na+-K+-ATP酶α1亚单位mRNA、Ca...     

肝硬化大鼠膈肌功能改变的实验研究

目的研究肝硬化大鼠膈肌损伤的作用机制。方法SD大鼠16只被随机分成对照组(n=8)和实验组(n=8)。实验组大鼠皮下注射40?l4制备肝硬化动物模型,共成模8只。应用体外灌流大鼠膈肌条的方法,分别测量其单收缩力(Pt),最大强直张力(Po),峰值收缩时间(CT),半舒张时间(1/2RT),张力最大上升速率( dT/dtmax),张力最大下降速率(-dT/dtmax),并测量在10、20、40、60、100Hz的张力,绘制力—频率曲线,同时测定膈肌组织中SOD、SDH、NOS、Na -K -ATPase、Ca2 -Mg2 ATPase的活性及MDA含量,并观察膈肌的形态学变化。结果肝硬化大鼠膈肌Pt,Po, dT/dtmax,-dT/dtmax均低于对照组(P<0.01);CT,1/2RT高于对照组(P<0.05);给予10、20、40、60、100Hz的电压刺激膈肌时,肝硬化大鼠膈肌张力明显低于对照组(P<0.05);肝硬化大鼠膈肌组织SOD、SDH、Na -K -ATPase,Ca2 -Mg2 ATPase活性明显低于对照组(P<0.05),而MDA含量和NOS活性显著高于对照组(P<0.05);肝硬化大鼠膈肌肌纤维断裂,溶解。结论肝硬化大鼠膈肌肌纤维结构受到破坏,收缩功能下降,可能与SOD,SDH,Na -K -ATPase,Ca2 -Mg2 ATPase活性降低,NOS活性和MDA含量增高有关。     

Effect of peroxisome proliferator-activated receptor gamma agonist on heart of rabbits with acute myocardial ischemia/reperfusion injury

Objective:To explore protective effect of rosiglitazone on myocardial ischemia reperfusion injury.Methods:A total of 48 male SD rats were randomly divided into control group(A),I/R group(B),high dose of rosiglitazone(C),low dose of rosiglitazone(D).Plasm concentration of creatine kinase(CK),CK-MB,hsCRP,Superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-Px),nitric oxide(NO)and endothelin(ET)were measured 1 h later after I/R.24 h after I/R hearts were harvested to observe pathological and ultrastructural changes.Immunohistochemistry and western blotting was used to test CD40 expression in myocardial tissue.Area of myocardial infarction were tested,arrhythmia rate during I/R was recorded.Results:Plasm concentration of creatine kinase(CK),CK-MB,hsCRP,NO,MDA and ET were decreased in group C,D compared with group B.Plasm concentration of T-SOD and GSHPx was increased significantly in group C,D compared with group B.Compared with group B,pathological and ultrastructural changes in group C,D were slightly.Myocardial infarction area and arrhythmia rate were lower in group C,D compare with group B.Conclusions:Rosiglitazone can protect myocardium from I/R injury by enhancing T-SOD and GSH-Px concentration,inhibit inflammatory reaction,improve endothelial function,reduce oxidative stress and calcium overload.     

灯盏细辛对大鼠心肌缺血再灌注心律失常和细胞凋亡的影响

目的观察灯盏细辛(breviscapine)对大鼠缺血/再灌注(I/R)时室性心律失常和心肌细胞凋亡的影响,并与缬沙坦(val-sartan)比较其作用效果。方法40只大鼠随机分为假手术组(Sham组)、I/R组、灯盏细辛组(Bre组)和缬沙坦组(Val组),以穿线结扎左冠状动脉前降支制备大鼠心肌I/R模型,观察各组室性心动过速(VT)、血清肌酸激酶同工酶(CK-MB)、心肌组织总超氧化物歧化酶(TSOD)及丙二醛(MDA)变化。流式细胞凋亡法检测心肌凋亡细胞(AI)及免疫组化法检测心肌P53和细胞色素C(Cyt-C)蛋白表达。结果I/R组VT和CK-MB、MDA均高于Sham组,而TSOD低于Sham组;与I/R组比较,Bre组、Val组VT和、CK-MB、MDA均有降低,而TSOD活性增加。Bre组和Val组AI和P53、Cyt-C蛋白表达水平显著低于I/R组(P<0.01)。结论灯盏细辛可降低VT,下调P53、Cyt-C蛋白表达,抑制细胞凋亡,与缬沙坦有相近的保护效果。     

L-精氨酸对糖尿病大鼠肝损伤的保护作用

目的探讨L-精氨酸(L-Arg)对糖尿病大鼠肝脏损伤的保护作用。方法给大鼠腹腔注射四氧嘧啶制备糖尿病模型,随机分为糖尿病组、L-Arg治疗组及正常对照组;用药4周末处死大鼠,检测肝细胞线粒体超氧化物歧化酶(Mn-SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性及丙二醛(MDA)含量,肝组织细胞一氧化氮合酶(NOS)、Na -K -ATPase、Ca2 -ATPase活性以及NO含量。结果与正常组比较,糖尿病组大鼠肝细胞线粒体Mn-SOD、GSH-Px活性明显降低,MDA含量显著升高,肝组织细胞内NOS、Na -K -ATPase、Ca2 -ATPase活性明显降低;与糖尿病组比较,L-Arg治疗组大鼠肝细胞线粒体Mn-SOD、GSH-Px活性明显升高,且肝组织细胞内NOS、Na -K -ATPase、Ca2 -ATPase活性及NO含量显著升高。结论L-Arg对糖尿病大鼠肝脏损伤具有一定的保护作用。     

步长稳心颗粒对大鼠心肌缺血再灌注心律失常的影响

目的:探索步长稳心颗粒对心肌缺血再灌注所致大鼠心律失常模型的作用。方法:结扎大鼠冠状动脉前降支得到心肌缺血再灌注心律失常模型,记录各组大鼠Ⅱ导联心电图,并测定心肌组织中Na -K -AT-Pase、Ca2 -Mg2 -ATPase的活性。结果:步长稳心颗粒对QRS时限、PR间期有稳定的作用,对抬高的ST段有降低的作用;能显著提高线粒体膜Na -K -ATPase、Ca2 -Mg2 -ATPase活性。结论:步长稳心颗粒可能是通过保持缺血-再灌注心肌细胞膜稳定性、改善缺血心肌能量代谢障碍以发挥其抗心律失常作用。     

Mibefradil, a T-Type Ca2+ Channel Blocker, Protects Against Mesenteric Ischemia-Reperfusion-Induced Oxidative Injury and Histologic Alterations in Intestinal Mucosa in Rats

The purpose of the present study was to investigate whether mibefradil can reduce oxidative stress and histologic damage in the rat small bowel subjected to mesenteric ischemia and reperfusion injury. Thirty Sprague-Dawley rats weighing between 210 and 220 g were divided into three groups, each containing 10 rats: group 1, sham operation; group 2, untreated ischemia-reperfusion; and group 3, ischemia-reperfusion plus mibefradil treatment group. Intestinal ischemia for 45 min and reperfusion for 60 min were applied. Ileal specimens were obtained to determine the tissue levels of MDA, CAT, SOD, and GSH-Px and histologic changes. In group 2, MDA values were significantly increased compared to those in groups 1 and 3. In addition, SOD, CAT, and GSH-Px values decreased significantly in group 2 compared to groups 1 and 3. The intestinal injury score increased significantly in group 2 and 3 rats compared to group 1 rats. However, this increase was reduced in group 3 rats compared to group 2. Histopathologically, the rats in group 1 had essentially normal testicular architecture. In group 2 rats, the lesions varied between grade 3 and grade 5. In contrast, most of the specimens in the mibefradil-treated group 3 showed grade 1 injury. Mibefradil plays a role in attenuating reperfusion injury of the small intestine by depressing free radical production and mucosal injury score and regulating postischemic intestinal perfusion while restoring intestinal microcirculatory blood flow and encountered histologic injury.     

Modulation of liver oxidant-antioxidant system by ischemic preconditioning during ischemia／reperfusion injury in rats

AIM: To investigate effects of ischemic pre-conditioning on the liver endogenous oxidant-antioxidant system during ischemia/reperfusion injury. METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into sham-operated (Sham), ischemia/ reperfusion (I/R), ischemic pre-conditioning plus ischemia/ reperfusion (IPC) groups. Serum ALT, AST and hyaluronic acid levels were assayed and pathologic alterations observed. Liver malondialdehyde (MDA) contents, endogenous antioxidant enzymes, superoxidase dismutase (SOD), catalase (CAT), gultathionine peroxidase (GSH-Px) activities, neutrophils accumulation marker, myeloperoxidase (MPO) activities were measured respectively. RESULTS: Compared with I/R group, sinusoidal endothelial cells as well as hepatocytes damages, as assessed biochemically and histochemically, were improved significantly in IPC group; neutrophils infiltration was also markedly reduced. In IPC group, liver peroxidation, as measured by MDA contents, was significantly decreased when compared with I/R group; endogenous antioxidant enzymes, SOD, CAT and GSH-Px activities were markedly higher than that in I/R group. CONCLUSION: Ischemic pre-conditioning exerts protective effects on both hepatic sinusoidal endothelial cells and hepatocytes during liver I/R injury. Its mechanisms may involve dimunition of neutrophils infiltration and modulation of the imbalance of endogenous oxidant-antioxidant system in the organism.     

Endoxin Antagonist Lessens Myocardial Ischemia Reperfusion Injury

OBJECTIVE: To elucidate whether endoxin is one of important factors involved in myocardial ischemia reperfusion (MIR) injury, the change of myocardial endoxin level was determined in rats with MIR injury model and the effects of anti-digoxin antiserum (ADA), an endoxin specific antagonist, on MIR injury were studied. METHODS: MIR injury model was obtained by ligating left anterior descending coronary artery 30 min followed by 45 min reperfusion. Sprague-Dawley rats were randomly divided into six groups of 10 rats, each. Sham group, MIR group, normal saline group, ADA 9, 18 and 36 mg.kg(-1). ECG was continuously recorded. After reperfusion left ventricular myocardium samples of ischemic area were processed immediately. Myocardial endoxin level, Na(+)-K(+)-ATPase, Ca(2+)-ATPase, Mg(2+)-ATPase activities, and intramitochondrial Ca(2+) content were measured. RESULTS: Myocardial endoxin level was significantly increased; Na(+)-K(+)-ATPase, Ca(2+)-ATPase, and Mg(2+)-ATPase activities were remarkably decreased; intramitochondrial Ca(2+) content was remarkably raised; ST segments of ECG were significantly elevated and occurrence and scores of ventricular arrhythmias were significantly increased in early stage of reperfusion in rats with MIR. In all groups with ADA, myocardial endoxin level was remarkably decreased; Na(+)-K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase activities were drastically increased; intramitochondrial Ca(2+) content was declined; ST segments and ventricular arrhythmias were improved. CONCLUSION: Myocardial endoxin level was increased in MIR, which implies that the elevated endoxin may be one of major factors inducing MIR injury. This postulate is supported by the observation that ADA has protective and therapeutic effects against MIR injury probably by antagonizing the action of endoxin. The underlying mechanism may be ascribed to restoration of energy metabolism, and attenuation of intracellular Ca(2+) overload.