Simultaneous,real-time measurement of nitric oxide and oxygen dynamics during cardiac ischemia-reperfusion of the rat utilizing sol-gel-derived electrochemical microsensors

In this study, we simultaneously measured nitric oxide (NO) and oxygen (O₂) dynamics in the myocardium during myocardial ischemia-reperfusion (IR) utilizing sol-gel modified electrochemical NO and O₂ microsensors. In addition, we attempted to clarify the correlation between NO release in the ischemic period and O₂ restoration in the myocardium after reperfusion, comparing a control heart with a remote ischemic preconditioning (RIPC)-treated heart as an attractive strategy for myocardial protection. Rat hearts were randomly divided into two groups: a control group (n = 5) and an RIPC group (n = 5, with RIPC treatment). Myocardia that underwent RIPC treatment (182 ± 70 nM, p < 0.05) released more NO during the ischemic period than those of the control group (63 ± 41 nM). The restoration value of oxygen tension (pO₂) in the RIPC group significantly increased and was restored to pre-ischemic levels (92.6 ± 36.8%); however, the pO₂ of the control group did not increase throughout the reperfusion period (5.7 ± 7.5%, p = 0.001). Myocardial infarct size measurements revealed a significant decrease in cell death in the myocardium region of the RIPC group (41.44 ± 6.42%, p = 0.001) compared with the control group (60.05 ± 10.91%). As a result, we showed that the cardioprotective effect of RIPC could be attributed to endogenous NO production during the ischemic period, which subsequently promoted reoxygenation in post-ischemic myocardia during early reperfusion. Our results suggest that the promotion of endogenous formation during an ischemic episode might be helpful as a therapeutic strategy for protecting the myocardium from IR injury. Additionally, our NO and O₂ perm-selective microsensors could be utilized to evaluate the effect of drug or treatment.     

4(6)-{2-[4-(2,3,4-三甲氧基苄基)哌嗪-1-基]-2-氧代乙氧基}芳甲酰胍类化合物的合成及其Na~+/H~+交换器1抑制活性

NHE1(Na+/H+交换器1)抑制剂对于心肌缺血再灌注损伤具有较好的保护作用.以苯(或吡啶)甲酰胍为母核,利用拼合原理,在苯(或吡啶)甲酰胍母环上引入4-(2,3,4-三甲氧基苄基)哌嗪-1-甲基,设计并合成了8个未见文献报道的目标化合物.其结构经MS,IR,1H NMR和元素分析确证.体外血小板肿胀模型(PSA)试验结果表明,大部分目标化合物显示出较好的NHE1抑制活性.     

中药复方和某种植物分泌液对脂质过氧化的抑制作用

利用发光测量法,研究了中药复方、植物分泌液(SL)和植物分泌液复方(SLIV)对Fe2+-亚麻油酸-BSA(牛血清白蛋白)和Fe2+-脑勺浆两个离体体系产生的脂质过氧化(LPO)有抑制作用,抑制程度与用药浓度有关.将中药复方应用于辐照模型,结果表明7Gy的γ射线辐照后小白鼠全血硒谷胱甘肽过氧化物酶(SeGSH-Px)活性降低,恢复缓慢,脑组织脂质过氧化加剧,而事先喂饲中药复方能显著提高SeGSH-Px水平,加速其活力恢复,增强脑组织抗氧化能力;将SL和SLIV应用于脑缺血重灌模型,结果显示沙土鼠脑缺血重灌后全血SeGSH-Px活力下降,血浆MDA上升,SeGSH-Px/MDA值降低,脑组织抗氧化能力下降,而事先喂饲SL、SLIV上述结果正相反,能明显提高机体的抗LPO能力.     

ROLE OF Na~+-Ca~(2+) EXCHANGE SYSTEM IN THE PATHOGENESIS OF MYOCARDIAL ISCHEMIA-REPERFUSION DAMAGE

Results from a systematic experiment on isolated perfused rat heart and isolated myc-cytes of adult rat showed that the mechanism of calcium influx during myocardial ischemia-reperfusion is due to the development of intracellular sodium overload during ischemic pe-riod, on reperfusion, the high intracellular Na~+ content activated the reverse direction ofNa~+-Ca~(2+) exchange over myocardial sarcolemma (SL), thus a large quantity of extracellularCa~(2+) fluxed over the SL to the intracellular space, forming a condition of intracellular Ca~(2+)overload, which leads to irreversible damage of the myocardium.     

Populus tomentiglandulosa Extract Is Rich in Polyphenols and Protects Neurons,Astrocytes, and the Blood-Brain Barrier in Gerbil Striatum Following Ischemia-Reperfusion Injury

Transient ischemia in brains causes neuronal damage, gliosis, and blood–brain barrier (BBB) breakdown, which is related to ischemia-induced brain dysfunction. Populus species have various pharmacological properties including antioxidant and anti-inflammatory activities. In this study, we found that phenolic compounds were rich in Populus tomentiglandulosa extract and examined the effects of Populus tomentiglandulosa extract on neuronal damage/death, astrogliosis, and BBB breakdown in the striatum, which is related to motor behavior, following 15-min transient ischemia in the forebrain in gerbils. The gerbils were pre-treated with 50, 100, and 200 mg/kg of the extract. The latter showed significant effects against ischemia-reperfusion injury. Ischemia-induced hyperactivity using spontaneous motor activity test was significantly attenuated by the treatment. Striatal cells (neurons) were dead at five days after the ischemia; however, pre-treatment with the extract protected the striatal cells from ischemia/reperfusion injury. Ischemia-induced reactive astrogliosis was significantly alleviated, in particular, astrocyte end feet, which are a component of BBB, were significantly preserved. Immunoglobulin G, which is not found in intact brain parenchyma, was apparently shown (an indicator of extravasation) in striatal parenchyma at five days after the ischemia, but IgG leakage was dramatically attenuated in the parenchyma by the pre-treatment. Based on these findings, we suggest that Populus tomentiglandulosa extract rich in phenolic compounds can be employed as a pharmaceutical composition to develop a preventive material against brain ischemic injury.     

Effects of Kynurenic Acid on the Rat Aorta Ischemia—Reperfusion Model: Pharmacological Characterization and Proteomic Profiling

Kynurenic acid (KYNA) is derived from tryptophan, formed by the kynurenic pathway. KYNA is being widely studied as a biomarker for neurological and cardiovascular diseases, as it is found in ischemic conditions as a protective agent; however, little is known about its effect after ischemia-reperfusion in the vascular system. We induced ischemia for 30 min followed by 5 min reperfusion (I/R) in the rat aorta for KYNA evaluation using functional assays combined with proteomics. KYNA recovered the exacerbated contraction induced by phenylephrine and relaxation induced by acetylcholine or sodium nitroprussiate in the I/R aorta, with vessel responses returning to values observed without I/R. The functional recovery can be related to the antioxidant activity of KYNA, which may be acting on the endothelium-injury prevention, especially during reperfusion, and to proteins that regulate neurotransmission and cell repair/growth, expressed after the KYNA treatment. These proteins interacted in a network, confirming a protein profile expression for endothelium and neuron repair after I/R. Thus, the KYNA treatment had the ability to recover the functionality of injured ischemic-reperfusion aorta, by tissue repairing and control of neurotransmitter release, which reinforces its role in the post-ischemic condition, and can be useful in the treatment of such disease.     

脑缺血再灌流后大鼠海马锥体细胞和星形胶质细胞的体视学

为了研究脑缺血再灌流后海马锥体细胞和星形胶质细胞的变化,选取24只SD大鼠,随机分为对照组、缺血再灌流后6、12、24 h组,采用Nissl染色,GFAP免疫组织化学方法并应用体视学参数分别对海马CA1、CA3区锥体细胞和星形胶质细胞进行形态学定量分析。结果显示,海马CA1、CA3区锥体细胞     

大鼠缺血再灌注损伤对心肌超微结构的影响及LXA4的保护作用

目的探讨脂氧素A4(LXA4)对大鼠心肌缺血再灌注损伤(MIRI)超微结构的保护作用.方法72只SD雄性大鼠随机分成假手术一组(C1组)、假手术二组(C2组)、MIRI一组(I/R1组)、MIRI二组(I/R2组)、MIRI前用药组(LX1组)、MIRI后用药组(LX2组),每组12只.建立大鼠MIRI模型,各组于开胸前取血(T1)、实验结束后取血(T2)测IL-1β、IL-8、cTnI血清浓度;同时测定SOD活性、MDA含量;TUNEL法检测心肌细胞凋亡率;电镜下观察心肌超微结构的变化.结果 I/R1、LX1与C1组相比,I/R2、LX2与C2组相比,血清IL-1β、IL-8、cTnI浓度(均为T2),SOD、MDA以及凋亡率增高(P<0.05).LX1与I/R1组,LX2与I/R2组相比,血清IL-1β、IL-8、cTnI浓度(均为T2),MDA含量及凋亡率均降低(均P<0.05);SOD活性提高(P<0.05);同时心肌超微结构损伤明显改善,线粒体排列整齐,电子密度增高,肿胀及空泡明显减轻.结论 LXA4通过抑制组织促炎细胞因子、氧自由基损伤,降低细胞凋亡来减轻心肌超微结构的损伤,对大鼠MIRI起明显的保护作用.     

益母草碱类似物设计、合成及其Na+/H+交换器-1抑制活性

以中药益母草中有效成分益母草碱为先导化合物,按生物电子等排原理,设计合成了18个益母草碱类似物.通过MS,1H NMR,13C NMR对化合物结构进行表征.初步的药效研究结果表明部分化合物具有Na+/H+交换器-1 (NHE-1)抑制活性,其中化合物1a和1e的活性显著强于阳性对照药Cariporide.     

4-[4-(2,3,4-三甲氧基苄基)哌嗪-1-基甲基]苯甲酰胍类化合物的合成 及其Na＋/H＋交换器1抑制活性

为了寻找对心肌缺血再灌注损伤具有保护作用的药物, 以苯甲酰胍为母核, 在其苯环的4位引入4-(2,3,4-三甲氧基苄基)哌嗪-1-甲基, 3位引入不同的取代苯甲酰胺基, 设计并合成了12个未见文献报道的目标化合物. 其结构经MS, IR, 1H NMR和元素分析确证. 体外血小板肿胀模型(PSA)试验结果表明, 大部分目标化合物显示出较好的Na＋/H＋交换器1 (NHE1)抑制作用, 其中化合物7g和7l抑制NHE1的IC50值分别为3.72和3.53 nmol&#8226;L－1, 是卡立泊来德(IC50＝12.1 nmol&#8226;L－1)的3.2和3.4倍.