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31.
目的 探讨降纤酶对脑缺血再灌注损伤的保护作用及其作用机制。方法 肾血管型高血压大鼠(RHR)70只,随机分为降纤酶组、对照组和伪手术组,按Longa氏方法改良复制成可再灌注的大脑中动脉闭塞(MCAO)模型,缺血2h 后恢复灌注。降纤酶组经股静脉给予降纤酶10U·kg-1体重,对照组给予等量的生理盐水。脑片行TTC及HE染色,观察两组在不同时间点的梗死灶的大小、脑微血管损害的表现及并发出血情况。结果 降纤酶组的梗死灶的体积较对照组明显缩小,脑微血管损害减轻,镜下出血灶减少。结论 降纤酶具有保护脑缺血再灌注损伤的作用。 相似文献
32.
缺血性脑卒中是一种急性脑血管病,目前主要的治疗手段是及时进行溶栓或取栓治疗以
实现血管再通,但这一过程会对脑血管造成严重的再灌注损伤,使血脑屏障的结构和功能受到破坏,增加脑出血的风险。有研究表明 Wnt/β-catenin 信号通路对血脑屏障的功能起重要调节作用,但Wnt/β-catenin 信号通路激活蛋白 R-spondin 对血脑屏障和脑损伤的调节作用尚不清楚。该文通过体外制备小鼠 R-spondin-1 重组蛋白,在小鼠原代脑血管内皮细胞中证实了 R-spondin-1 蛋白协同 Wnt3a蛋白对 Wnt/β-catenin 信号通路的激活作用,并发现 R-spondin-1 能够显著改变血脑屏障功能相关基因Cldn3 和 Plvap 的表达水平;在小鼠脑缺血再灌注模型中,静脉注射 R-spondin-1 重组蛋白具有降低
脑组织梗死和提高小鼠存活率的趋势,但与生理盐水对照组相比未达到显著性差异。另外,该文还报道了 R-spondin 蛋白对血脑屏障功能的分子作用机制,并初步鉴定了其对卒中后脑损伤的治疗效果和
临床应用潜力。 相似文献
33.
介绍了岭脚大桥悬臂灌注施工过程中箱梁挠度的变化,并分析了挠度的影响因素,根据桥面挠度变化特点及影响因素在悬臂施工中制定了相应的控制措施,以提高岭脚大桥箱梁的施工质量,从而保证桥的质量。 相似文献
34.
35.
Yuhei Oi Tomohisa Nagoshi Haruka Kimura Yoshiro Tanaka Akira Yoshii Rei Yasutake Hirotake Takahashi Yusuke Kashiwagi Toshikazu D. Tanaka Toshiaki Tachibana Michihiro Yoshimura 《International journal of molecular sciences》2022,23(15)
Increasing evidence suggests natriuretic peptides (NPs) coordinate interorgan metabolic crosstalk. We recently reported exogenous ANP treatment ameliorated systemic insulin resistance by inducing adipose tissue browning and attenuating hepatic steatosis in diet-induced obesity (DIO). We herein investigated whether ANP treatment also ameliorates myocardial insulin resistance, leading to cardioprotection during ischemia–reperfusion injury (IRI) in DIO. Mice fed a high-fat diet (HFD) or normal-fat diet for 13 weeks were treated with or without ANP infusion subcutaneously for another 3 weeks. Left ventricular BNP expression was substantially reduced in HFD hearts. Intraperitoneal-insulin-administration-induced Akt phosphorylation was impaired in HFD hearts, which was restored by ANP treatment, suggesting that ANP treatment ameliorated myocardial insulin resistance. After ischemia–reperfusion using the Langendorff model, HFD impaired cardiac functional recovery with a corresponding increased infarct size. However, ANP treatment improved functional recovery and reduced injury while restoring impaired IRI-induced Akt phosphorylation in HFD hearts. Myocardial ultrastructural analyses showed increased peri-mitochondrial lipid droplets with concomitantly decreased ATGL and HSL phosphorylation levels in ANP-treated HFD, suggesting that ANP protects mitochondria from lipid overload by trapping lipids. Accordingly, ANP treatment attenuated mitochondria cristae disruption after IRI in HFD hearts. In summary, exogenous ANP treatment ameliorates myocardial insulin resistance and protects against IRI associated with mitochondrial ultrastructure modifications in DIO. Replenishing biologically active NPs substantially affects HFD hearts in which endogenous NP production is impaired. 相似文献
36.
David R. Janero 《Critical reviews in food science and nutrition》1995,35(1-2):65-81
The disease state of myocardial ischemia results from a hypoperfusion‐induced insufficiency of heart‐muscle oxidative metabolism due to inadequate coronary circulation. Myocardial ischemia is an important, lifespan‐limiting medical problem and a major economic health‐care concern. Reperfusion, although avidly pursued in the clinic as essential to the ultimate survival of acutely ischemic heart muscle, may itself cany an injury component Cardiac reperfusion injury appears to reflect, at least in part, an oxidant burden established upon reoxygenation of ischemic myocardium. Laboratory evidence demonstrates that oxidative stress to the heart‐muscle cell (cardiomyocyte) can elicit the three known types of ischemia‐reperfusion injury that directly affect the myocardium: arrhythmia, stunning, and infarction. The limited clinical occurrence of serious reperfusion arrhythmias has restricted the importance of antioxidants as antiarrhythmic agents against this form of myocardial ischemia‐reperfusion damage. Despite the utmost clinical significance of lethal cardiomyocyte injury as a negative prognostic indicator for the ischemic heart‐disease patient, inconsistent results of antioxidant interventions in reducing infarct size have somewhat tempered interest in antioxidant infarct trials. By contrast, the negative clinical consequences of stunning may indeed be preventable by utilizing antioxidants to help restore postischemic cardiac pump function. Several as yet unanswered questions remain regarding oxidative stress in the reperfused heart, its significance to cardiomyocyte damage, and its ability to elicit specific postischemic myocardial derangements. Targeted mechanistic studies are required to address these questions and to define the pathogenic role of oxidative stress (and, hence, the therapeutic potential of antioxidant intervention) in myocardial ischemia‐reperfusion injury. The overall aim of current research in this area is to enable the cardiac surgeon/cardiologist to advance beyond the largely palliative drugs now available for management of the coronary heart‐disease patient and attack directly the pathogenic determinants of heart‐muscle ischemia‐reperfusion injury. Optimal use of antioxidants may help address this important medical need. 相似文献
37.
Jean Selim Mouad Hamzaoui Antoine Ghemired Zoubir Djerada Laurence Chevalier Nicolas Piton Emmanuel Besnier Thomas Clavier Anaïs Dumesnil Sylvanie Renet Paul Mulder Fabien Doguet Fabienne Tamion Benoît Veber Jrmy Bellien Vincent Richard Jean-Marc Baste 《International journal of molecular sciences》2022,23(16)
The routine use of mechanical circulatory support during lung transplantation (LTx) is still controversial. The use of prophylactic human albumin (HA) or hypertonic sodium lactate (HSL) prime in mechanical circulatory support during LTx could prevent ischemia–reperfusion (IR) injuries and pulmonary endothelial dysfunction and thus prevent the development of pulmonary graft dysfunction. The objective was to investigate the impact of cardiopulmonary bypass (CPB) priming with HA and HSL compared to a CPB prime with Gelofusine (GF) on pulmonary endothelial dysfunction in a lung IR rat model. Rats were assigned to four groups: IR-CPB-GF group, IR-CPB-HA group, IR-CPB-HSL group and a sham group. The study of pulmonary vascular reactivity by wire myograph was the primary outcome. Glycocalyx degradation (syndecan-1 and heparan) was also assessed by ELISA and electron microscopy, systemic and pulmonary inflammation by ELISA (IL-1β, IL-10, and TNF-α) and immunohistochemistry. Clinical parameters were evaluated. We employed a CPB model with three different primings, permitting femoral–femoral assistance with left pulmonary hilum ischemia for IR. Pulmonary endothelium-dependent relaxation to acetylcholine was significantly decreased in the IR-CPB-GF group (11.9 ± 6.2%) compared to the IR-CPB-HA group (52.8 ± 5.2%, p < 0.0001), the IR-CPB-HSL group (57.7 ± 6.3%, p < 0.0001) and the sham group (80.8 ± 6.5%, p < 0.0001). We did not observe any difference between the groups concerning glycocalyx degradation, and systemic or tissular inflammation. The IR-CPB-HSL group needed more vascular filling and developed significantly more pulmonary edema than the IR-CPB-GF group and the IR-CPB-HA group. Using HA as a prime in CPB during Ltx could decrease pulmonary endothelial dysfunction’s IR-mediated effects. No effects of HA were found on inflammation. 相似文献
38.
Shu-Er Yang Jin-Cherng Lien Chia-Wen Tsai Chi-Rei Wu 《International journal of molecular sciences》2022,23(18)
Isoflavones have been widely studied and have attracted extensive attention in fields ranging from chemotaxonomy and plant physiology to human nutrition and medicine. Isoflavones are often divided into three subgroups: simple O-substituted derivatives, prenylated derivatives, and glycosides. Simple O-substituted isoflavones and their glycosides, such as daidzein (daidzin), genistein (genistin), glycitein (glycitin), biochanin A (astroside), and formononetin (ononin), are the most common ingredients in legumes and are considered as phytoestrogens for daily dietary hormone replacement therapy due to their structural similarity to 17-β-estradiol. On the basis of the known estrogen-like potency, these above isoflavones possess multiple pharmacological activities such as antioxidant, anti-inflammatory, anticancer, anti-angiogenetic, hepatoprotective, antidiabetic, antilipidemic, anti-osteoporotic, and neuroprotective activities. However, there are very few review studies on the protective effects of these novel isoflavones and their related compounds in cerebral ischemia reperfusion. This review primarily focuses on the biosynthesis, metabolism, and neuroprotective mechanism of these aforementioned novel isoflavones in cerebral ischemia reperfusion. From these published works in in vitro and in vivo studies, simple O-substituted isoflavones could serve as promising therapeutic compounds for the prevention and treatment of cerebral ischemia reperfusion via their estrogenic receptor properties and neuron-modulatory, antioxidant, anti-inflammatory, and anti-apoptotic effects. The detailed mechanism of the protective effects of simple O-substituted isoflavones against cerebral ischemia reperfusion might be related to the PI3K/AKT/ERK/mTOR or GSK-3β pathway, eNOS/Keap1/Nrf-2/HO-1 pathway, TLRs/TIRAP/MyD88/NFκ-B pathway, and Bcl-2-regulated anti-apoptotic pathway. However, clinical trials are needed to verify their potential on cerebral ischemia reperfusion because past studies were conducted with rodents and prophylactic administration. 相似文献
39.
Nora A. Spraakman Annemieke M. Coester Arno R. Bourgonje Vincent B. Nieuwenhuijs Jan-Stephan F. Sanders Henri G. D. Leuvenink Harry van Goor Gertrude J. Nieuwenhuijs-Moeke 《International journal of molecular sciences》2022,23(17)
During ischemia–reperfusion injury (IRI), reactive oxygen species are produced that can be scavenged by free sulfhydryl groups (R-SH, free thiols). In this study, we hypothesized that R-SH levels decrease as a consequence of renal IRI and that R-SH levels reflect post-transplant graft function. Systemic venous, arterial, renal venous, and urinary samples were collected in donors and recipients before, during, and after transplantation. R-SH was measured colorimetrically. Systemic arterial R-SH levels in recipients increased significantly up to 30 sec after reperfusion (p < 0.001). In contrast, renal venous R-SH levels significantly decreased at 5 and 10 min compared to 30 sec after reperfusion (both p < 0.001). This resulted in a significant decrease in delta R-SH (defined as the difference between renal venous and systemic arterial R-SH levels) till 30 sec after reperfusion (p < 0.001), indicating a net decrease in R-SH levels across the transplanted kidney. Overall, these results suggest trans-renal oxidative stress as a consequence of IRI during kidney transplantation, reflected by systemic and renal changes in R-SH levels in transplant recipients. 相似文献
40.
Lina Jakubauskiene Matas Jakubauskas Gintare Razanskiene Bettina Leber Jennifer Weber Lisa Rohrhofer Diana Ramasauskaite Kestutis Strupas Philipp Stiegler Peter Schemmer 《International journal of molecular sciences》2022,23(13)
Successful uterus transplantation, a potential treatment method for women suffering from absolute uterine infertility, is negatively affected by ischemia–reperfusion injury (IRI). The aim of this study is to investigate the protective effect of relaxin (RLX) or/and erythropoietin (EPO) on experimental uterus IRI. Eighty rats, randomly assigned into eight groups (n = 10/group), were pretreated with either saline, 5 μg/kg human relaxin-2, 4000 IU/kg recombinant human erythropoietin or their combination. Ischemia was achieved by clamping the aorta and ovarian arteries for 60 min, following 120 min of reperfusion and tissue sampling. For sham animals, clamping was omitted during surgery. There were no differences in tissue histological score, malondialdehyde (MDA) and superoxide dismutase (SOD) levels, myeloperoxidase (MPO) and TUNEL-positive cell count between all sham-operated rats. Pretreatment with RLX preserved normal tissue morphology, reduced MDA levels, MPO and TUNEL-positive cell count, preserved SOD activity and upregulated NICD and HES1 gene expression when compared to the control group. Pretreatment with EPO reduced MDA levels. In conclusion, pretreatment with RLX, EPO or a combination of both EPO and RLX significantly alleviates uterine tissue damage caused by IRI. 相似文献