心肌肽素对异丙肾上腺素致损伤大鼠心肌的保护作用

目的：观察心肌肽素对异丙肾上腺素致损伤大鼠心肌的保护作用。方法：在大剂 量异丙肾上腺素致大鼠心肌损伤模型上,观察心肌肽素对驻肌形态及脂质过氧化的影响。结果：心肌肽素可明显减轻受损心肌的变性坏死反应和减少炎性细胞浸润,非常显著地降低心肌丙二醛含量、提高心肌超氧化物歧化酶活性。结论：心肌肽素对异丙肾上腺素损伤大鼠心肌有保护作用,这可能与其抗脂质过氧化作用有关。     

牛磺酸对大鼠异丙肾上腺素心肌损伤的保护作用

大鼠皮下注射异丙肾上腺素(40mg/kg/日)造成心肌损伤模型,发现心肌组织钙含量和心肌AGTⅡ水平显著增加,并伴有严重的心肌损伤。若同时注射牛磺酸(200mg/kg/日)或疏甲丙辅酸(1mg/kg/日)均可拮抗异丙肾上腺素引起的心肌钙增加及AGTⅡ水平升高,并可缓解心肌组织病理损伤。结果提示牛磺酸抑制心肌AGTⅡ可能是其拮抗异丙肾上腺素心肌损伤的重要机制之一。     

阿司匹林,卡托普利及二者合用对豚鼠心肌活性氧损伤的保护作用

用黄嘌呤黄嘌呤氧化酶系统产生活性氧，诱发豚鼠右室前乳头肌氧化损伤，通过动物实验观察了阿司匹林，卡托普利及Ａｓｐ＋Ｃａｐ对心肌活性氧损伤的保护作用。发现Ａｓｐ对Ｘ／ＸＯ诱导的心乳头肌收缩性，不应期，兴奋性和自律性的变化，以及心肌ＳＯＤ活性降低，ＭＤＡ含量升高，无显著抑制作用；     

肾交感神经去除术对心肌肥厚和心肌纤维化的影响

目的:观察肾交感神经去除术（renalsympatheticdenervation,RDN）对心肌肥厚和心肌纤维化的影响,并探讨其可能机制。方法:选用12周龄的健康SD雄性大鼠60只,随机分为假手术组、假手术+RDN组、主动脉缩窄组、主动脉缩窄+RDN组,8周后用介入生理记录仪检测血流动力学和心功能指标,HE染色、苦味酸-天狼星红染色分别观察心肌肥厚和心肌纤维化情况,放射免疫分析法测量血浆肾上腺素浓度、肾素活性、血管紧张素II浓度及心脏血管紧张素II含量。结果:与主动脉缩窄组相比,RDN可显著改善主动脉缩窄大鼠心脏舒张功能［左室舒张末期压力（LVEDP）：(8.03±1.66)mmHgvs(15.77±2.14)mmHg;等容舒张期左室压力下降最大速率（-dp/dt）：(7793±587)mmHg/svs(6353±475)mmHg/s;P＜0.01］、防止其心肌肥厚和纤维化［左心室重量指数：3.340±0.121vs4.244±0.102;心肌细胞面积：(332.9±28.9)μm2vs(401.6±33.2)μm2;胶原容积分数：7.76%±0.85%vs12.48%±1.82%;P＜0.01］。然而,RDN不能降低主动脉缩窄大鼠的血压（P＞0.05）。RDN导致主动脉缩窄大鼠的血浆肾上腺素浓度、肾素活性、血管紧张素II浓度及心脏血管紧张素II含量均明显减少（P＜0.01）。结论:RDN可以通过降低交感和肾素-血管紧张素系统活性直接抑制心肌肥厚和心肌纤维化,从而改善心脏功能。     

IGF-1对窒息新生儿心肌损伤的保护作用

目的探讨胰岛素样生长因子-1(IGF-1)对窒息后心肌损伤的保护作用.方法选择18例窒息后伴心肌损伤的新生儿,其中轻度窒息11例,重度窒息7例,均为足月适于胎龄儿,分别在急性期和恢复期取外周静脉血,用于IGF-1和CK-MB测定.12例正常足月儿作为对照.IGF-1用ELISA法测定,CK-MB用电-化学发光法测定.结果窒息患儿急性期CK-MB显著高于对照组及恢复期,IGF-1显著低于对照组及恢复期(P均＜0.01),重度窒息组CK-MB高于轻度窒息组(P＜0.01),而IGF-1低于轻度窒息组(P＜0.05).IGF-1与CK-MB呈中度负相关(r＝-0.600,P＝0.000).结论 IGF-1参与了窒息损伤病理过程,且对窒息后心肌损伤有保护作用.IGF-1及CK-MB可作为预测窒息严重程度的指标.     

甘氨酸抗心肌损伤作用及机制研究

目的 :研究甘氨酸抗心肌损伤的作用及机制。方法 :(1)取体重为 (2 5 0± 30 )g的雄性健康SD大鼠 2 2只 ,随机分成 3组 :正常对照组 (n =7) ,内毒素组 (n =7) ,甘氨酸 +内毒素组 (n =8) ,在Langendorff装置上用Krebs -Henseleit(KH)液对大鼠离体心脏行主动脉逆灌。连续记录心肌细胞单相动作电位 (MAP)、心肌收缩张力曲线 ;(2 )取健康成年雄性SD大鼠心脏做冰冻切片 ,分为 4组 :脊髓阴性对照组 (不含任何抗体的PBS)、脊髓阳性对照组 (一抗为抗甘氨酸受体组 )、心肌细胞阴性对照组、心肌细胞抗甘氨酸受体组。冰冻切片进行免疫组化荧光染色…     

槲皮素对柔红霉素所致心肌损伤的保护作用

目的观察槲皮素(QUE)对柔红霉素(DNR)所致小鼠心肌损伤的保护作用．方法52只小鼠分5个实验组，1组作为空白对照组．1组用DNR诱导小鼠心肌损伤；1组用QUE灌胃给药后再用DNR诱导心肌损伤作为保护组；1组只给QUEE灌胃作为保护对照组；1组给予DMSO灌胃作为溶剂对照组．观察各组小鼠的血清心肌酶谱、心肌和血清中脂质过氧化产物丙二醛(MDA)的含量及超氧化物歧化酶(SOD)活性的变化．观察心脏大体改变．并制备病理切片，HE染色后，光镜下观察心肌形态学变化．结果DNR组小鼠的血清心肌酶谱显著升高．血清和心肌中MDA含量显著增高，SOD活性降低，引起心脏充血、水肿．心肌颗粒变性．灶性出血、坏死．而QUE保护组的心肌酶升高程度明显降低、血清和心肌组织中MDA含量无明显增加，SOD活性不降低，心肌无明显出血灶及颗粒变性．结论槲皮素对柔红霉素诱导的小鼠心肌损伤有保护作用．其机理可能与清除氧自由基、抗脂质过氧化损伤有关．     

参附注射液对缺氧复氧损伤心肌的保护作用及机制研究

随着心肌缺血治疗过程中多种血管再通技术的广泛应用。由此引起的心肌再灌注损伤(myocardial reperfusion injury;MRI)问题亦日趋突出。因而探索心肌缺血再灌注损伤的机制和防治措施,已成为当今医学研究的热点之一。     

褪黑素对帕金森病模型大鼠代谢机能和DA能神经元的保护作用

目的我们前期研究证实6-羟基多巴胺(6-OHDA)明显诱导性帕金森病(PD)模型大鼠行为学障碍及其纹状体神经元的损伤。目前进一步借助褪黑素(MT)探查证实6-羟基多巴胺对PD模型大鼠纹状体代谢机能损害和黑质DA能神经元的保护作用。方法选取55只成年雄性SD大鼠,并随机分成正常对照组(包括正常对照和稀释剂对照)、6-OHDA处理组和6-OHDA+MT处理组,实验借助Micro PET-CT、免疫组织化学染色及Westernblot技术检测和比较实验大鼠纹状体代谢、TH阳性纤维密度及TH蛋白表达量的变化。所获得数据使用SPSS20.0统计学软件进行分析处理,P0.05为有统计学意义。结果 Micro PET-CT检测结果显示,6-OHDA组大鼠纹状体糖代谢机能(1.34±0.114)明显较对照组(4.36±0.114)低(P=0.00),而6-OHDA+MT处理组(4.14±0.114)与6-OHDA组相比糖代谢机能增高,差异也具有统计学意义(P=0.00)。纹状体内TH阳性纤维密度和TH蛋白表达水平在6-OHDA组(分别为0.324±0.018、0.434±0.338)均显著低于对照组(0.378±0.026、1.626±0.526)(P=0.00,P=0.00)和6-OHDA+MT处理组(0.37±0.010、1.136±0.494)(P=0.00,P=0.03),但对照组和6-OHDA+MT处理组之间差异无统计学意义(P=0.52,P=0.12)。结论褪黑素对PD模型大鼠纹状体代谢机能障碍和中脑黑质DA能神经元损伤具有一定的保护作用。     

槲皮素对柔红霉素所致心肌损伤的保护作用

目的观察槲皮素(QUE)对柔红霉素(DNR)所致小鼠心肌损伤的保护作用.方法 52只小鼠分5个实验组,1组作为空白对照组.1组用DNR诱导小鼠心肌损伤;1组用QUE灌胃给药后再用DNR诱导心肌损伤作为保护组;1组只给QUE灌胃作为保护对照组;1组给予DMSO灌胃作为溶剂对照组.观察各组小鼠的血清心肌酶谱、心肌和血清中脂质过氧化产物丙二醛(MDA)的含量及超氧化物歧化酶(SOD)活性的变化.观察心脏大体改变,并制备病理切片,HE染色后,光镜下观察心肌形态学变化.结果 DNR组小鼠的血清心肌酶谱显著升高,血清和心肌中MDA含量显著增高,SOD活性降低,引起心脏充血、水肿,心肌颗粒变性,灶性出血、坏死.而QUE保护组的心肌酶升高程度明显降低、血清和心肌组织中MDA含量无明显增加,SOD活性不降低,心肌无明显出血灶及颗粒变性.结论槲皮素对柔红霉素诱导的小鼠心肌损伤有保护作用.其机理可能与清除氧自由基、抗脂质过氧化损伤有关.     

Demonstration of alpha-adrenergic coronary control in different layers of canine myocardium by regional myocardial sympathectomy

Summary The direct effects of sympathetic coronary innervation in conscious dogs were analyzed by comparison of myocardial blood flow in a sympathectomized section of the left ventricle with blood flow in another section of the same ventricle with intact sympathetic innervation. Regional myocardial sympathectomy was accomplished by a protocol of intracoronary application of 6-hydroxydopamine (6-OHDA). Regional adrenergic nerve function was checked by studies on accumulation, retention and stimulus-induced release of labelled norepinephrine together with studies on regional ventricular contractility during stellate ganglion stimulation. These tests demonstrated complete sympathectomy in the 6-OHDA-treated section and an unimpaired adrenergic nerve function in the untreated control section.In these dogs at rest, myocardial blood flow (MBF) was 66±14 ml/min·100 g in the left ventricular control section and 108±16 ml/min·100 g in the 6-OHDA-treated section. Transmural distribution of MBF was similar in these two sections: subendocardial MBF/subepicardial MBF was 1.28±0.17 in the control section and 1.36±0.12 in the 6-OHDA-treated section. Application of 1.0 mg/kg propranolol i.v. did not modify MBF and its distribution in either section. Following 1.0 mg/kg phentolamine i.v., MBF in the control section approached that in the 6-OHDA-treated sympathectomized section.These results demonstrate that a substantial -adrenergic constrictive coronary tone is operative in the ventricular control section in these conscious dogs at rest, which is of similar magnitude in different layers of the left ventricular wall.Supported by Deutsche Forschungsgemeinschaft     

Influence of thoracic sympathectomy on cardiac induced oscillations in tissue blood volume

The photoplethysmographic (PPG) signal, which measures cardiac-induced changes in tissue blood volume by light transmission measurements, shows spontaneous fluctuations. In this study, PPG was simultaneously measured in the right and left index fingers of 16 patients undergoing thoracic sympathectomy, and, from each PPG pulse, the amplitude of the pulse (AM) and its maximum (BL) were determined. The parameter AM/BL is proportional to the cardiac-induced blood volume increase, which depends on the arterial wall compliance. AM/BL increased after the thoracic sympathectomy treatment (for male patients, from 2.60±1.49% to 4.81±1.21%), as sympathetic denervation decreases arterial tonus in skin. The very low-frequency (VLF) fluctuations of BL or AM showed high correlation (0.90±0.11 and 0.92±0.07, respectively) between the right and left hands before the thoracic sympathectomy, and a significant decrease in the right-left correlation coefficient (to 0.54±0.22 and 0.76±0.20, respectively) after the operation. The standard deviation of the BL or AM VLF fluctuations also reduced after the treatment, indicating sympathetic mediation of the VLF PPG fluctuations. The study also shows that the analysis of the PPG signal and the VLF fluctuations of the PPG parameters enable the assessment of the change in sympathetic nervous system activity after thoracic sympathectomy.     

Substrate mobilization during prolonged exercise in 6-hydroxydopamine treated rats

Summary Exercise-induced lipolysis and glycogenolysis were studied in rats that had undergone chemical sympathectomy, surgical adrenomedullectomy, or a combination of these treatments. Sympathectomy was accomplished by injection of 6-hydroxydopamine. The exercise test administered immediately prior to sacrifice consisted of running 90 min (30 min at 22.5, 28.5, and 32.0 m/min, respectively, without interruption). Control animals were sacrificed at rest. Lipolysis, as measured by the rise in plasma and adipose tissue free fatty acid levels, was significantly (P<0.01) elevated over control values in all exercised groups. However, progressive (P<0.05) depression in lipolysis occurred as adrenergic control was successively eliminated. No treatment completely inhibited lipolysis or reduced work capacity. None of the treatments inhibited liver or muscle glycogenolysis in the exercised animals. The results demonstrate that prolonged exercise induces significant lipolysis and glycogenolysis in the rat after treatments designed to eliminate the sympathetic control over these processes. These data point to factors other than the adrenergic system as playing a role in substrate mobilization during endurance exercise.     

Post-infarct cardiac sympathetic hyperactivity regulates galanin expression

The neuropeptide galanin is elevated in the cardiac sympathetic innervation after myocardial infarction (MI). Galanin inhibits vagal transmission and may support the regeneration of sympathetic nerves, thereby contributing to the development of arrhythmia and sudden cardiac death after MI. The reason for increased galanin production in sympathetic neurons after myocardial infarction is not known. Cardiac sympathetic neurons are activated chronically after cardiac ischemia–reperfusion, and activation of sympathetic neurons in culture stimulates galanin expression. Therefore, we tested the hypothesis that increased sympathetic nerve activity stimulates galanin expression in cardiac sympathetic neurons after myocardial infarction. To test this hypothesis we used TGR(ASrAOGEN) transgenic rats, which lack brain angiotensinogen and do not exhibit post-infarct sympathetic hyperactivity. Hearts and stellate ganglia were collected 1 week after ischemia–reperfusion. Galanin mRNA was quantified by real-time PCR and peptide content was assayed by enzyme-linked immunosorbent assay. Galanin mRNA increased approximately 3-fold after MI in cardiac sympathetic neurons of both genotypes compared to unoperated and sham controls. Left ventricular galanin content, however, increased after MI only in Sprague–Dawley rats and not in AOGEN rats. These data suggest that post-infarct cardiac sympathetic hyperactivity stimulates galanin peptide production but is not required for increased galanin mRNA expression.     

Organization of brainstem noradrenaline hyperinnervation following neonatal 6-hydroxydopamine treatment in rat

Summary The organization and origin of NA axonal sprouting in individual brainstem nuclei was examined by fluorescence histochemistry and a radioenzymatic assay for noradrenaline (NA) in adult rats which were administered 6-hydroxydopamine (6-OHDA) as neonates. Significant 2–6 fold increases in NA content were measured in primary sensory nuclei, associational nuclei, somatic motor and visceral cranial nerve nuclei, reticular formation, raphe nuclei, and the inferior olivary complex. Fluorescence histochemical analysis reveals a major increase in the number of fluorescent fibers in most areas of the brainstem after 6-OHDA treatment. The normal pattern of innervation and axon morphology of each nucleus is retained after drug treatment. Bilateral locus coeruleus (LC) lesions in treated animals results in the denervation of only those nuclei which normally receive LC innervation (Levitt and Moore, 1979). The increased number of NA-containing axons in nuclei innervated by the lateral tegmental cell groups (LT) remains intact after LC ablation.The present results indicate that the brainstem NA sprouting following neonatal 6-OHDA administration occurs in a highly specified manner. The brainstem projections of both the LC and LT neuron groups exhibit marked axonal growth which is restricted to their specific brainstem terminal fields and probably occurs in response to the denervation of their respective, more rostral target areas.     

Neonatal noradrenaline depletion prevents the transition of Bergmann glia in the developing cerebellum

The influence of neonatal administration of 6-hydroxydopamine (6-OHDA) on the cell proliferation in cerebellum was studied using 10–30 days-old rats. Compared to their littermates, treated rats had poor ability in searching, skills performance and orienting in the new environment. Elimination of noradrenergic terminals by 6-OHDA led to a delay in granular cell migration. The secondary foliation in neo-cerebellum was absent. The Bergmann glial cells were abnormally located, structurally different and did not form the intimate association with Purkinje cells. Our findings indicate that without noradrenergic influence neurones and glial cells do not proliferate normally and noradrenaline may act as an important trophic factor also for Bergmann glial cells.     

Neonatal sympathectomy by 6-hydroxydopamine: cardiovascular responses in the paralyzed rat

Rats who had been neonatally sympathectomized by peripheral injections of 6-hydroxydopamine or vehicle were paralyzed by succinylcholine and received either atropine or saline injection. Heart rate and blood pressure responses to foot shocks and to a conditioned stimulus (CS) for shock were continuously recorded. Sympathectomized rats showed lower basal systolic blood pressure, less second to second blood pressure variability and attenuated pressor responses to the shock and the CS. Basal heart rate and the heart rate response to shock were were unaffected by sympathectomy, but cardiac rate deceleration to the CS was ablished. Atropine increased basal heart rate, decreased heart rate variability and abolished the cardiac deceleration to the CS. These data were interpreted as suggesting that conditioned cardiac deceleration in the rat is a vagal mediated response compensatory to prior blood pressure increases. Sympathectomized rats also showed higher core temperatures under paralysis.     

Control of the Neurotoxicity of 6-Hydroxydopamine by Intraneuronal Noradrenaline in Rat Iris

In vitro studies with the neurotoxic compounds 6-hydroxydopamine (6-OH-DA) and 6-aminodopamine (6-A-DA) showed that noradrenaline (NA) markedly inhibited the autooxidation of 6-OH-DA, but not of 6-A-DA. In vivo studies of the adrenergic nerves in rat iris showed that the neurotoxic potency of 6-OH-DA, but not 6-A-DA, was increased after NA depletion by α-methyl-p-tyrosine methylester(H44/68). Neurotoxicity was evaluated by measuring the associated decrease in ³H-NA uptake. lntraocular injection of NA counteracted the degenerative action of 6-OH-DA in both untreated and H44168 pretreated rats. Intraocular NA did not interfere with the neurotoxicity of 6-A-DA. Additionally, octopamine did not affect the rate of autooxidation nor the neurotoxic potency of 6-OH-DA or 6-A-DA. Control experiments with ³H-6-OH-DA showed that the intraneuronal NA levels did not significantly affect the intraneuronal accumulation of 6-OH-DA. The parallelism between the in vitro results on autooxidation and in vivo data on neurotoxicity makes it appear that the neurotoxic potency of 6-OH-DA and 6-A-DA is closely associated with their rates of autooxidation. The control of the degenerative action of 6-OH-DA by intraneuronal NA may be mediated via reaction of NA with radicals formed from oxygen during autooxidation of 6-OH-DA.