非编码RNA在脑缺血再灌注损伤中的作用

脑卒中(stroke)是导致成年人残疾和死亡的第二大病因,缺血性脑卒中约占所有脑卒中病例的87％[1],成为了现代社会健康和生活质量的主要威胁.缺血性脑卒中(ischemic stroke)由于脑血流量严重减少,脑组织缺乏血液和氧气供应,最终导致神经元细胞死亡和脑梗死[2].目前临床上常用的治疗缺血性脑卒中的方法是及时...     

雷帕霉素促进缺血性脑卒中后神经血管单位修复

正脑卒中(cerebral stroke)是一种由脑血管病变引起的、以脑组织损伤及相应神经功能缺陷为主要临床表现的急性脑血管病,可分为缺血性和出血性2种,该病具有致残率高、死亡率高和发病率高的特点~([1])。我国每年脑卒中新发病例超过200万,约有120万人死于脑卒中相关疾病,脑卒中已经成为了家庭和社会的沉重负担~([2])。由于仅有的溶栓药物组织     

正五聚环蛋白3在缺血性中风发病中的作用研究进展

<正>研究表明脑缺血损伤是一种损伤级联反应,即兴奋性氨基酸毒性释放,梗死区周围去极化,程序性细胞死亡和炎性反应~([1]),其中炎性级联反应在急性缺血性卒中(acute ischemic stroke,AIS)的进展中起至关重要的作用~([2])。脑缺血可诱导多种促炎介质的表达,如细胞因子,包括肿瘤坏死因子TNF-α、白介素IL-1β、IL-10和黏附分子(ICAM)等,在中枢神经系统炎性反应的扩散和持续方面起着重要的作用~([3])。急     

长链非编码RNA与缺血性脑卒中研究进展*

正缺血性脑卒中(ischemic stroke)是一种脑供血不足导致的脑组织坏死,治疗窗口短、早期诊断缺乏、死亡及致残率高,严重危害中老年人健康。目前,缺血性脑卒中分子机制仍不明确,早期诊断标志物缺乏,迫切需要寻找有效预防手段,积极诊断方法和快速救治措施。长链非编码RNA(long non-coding RNA, lncRNA)是长度大于200个核苷酸且无编码功能的分子。lncRNA参与增殖分化、凋亡自噬等生物学过程,于转录水平和转录后水平调控表达。近年,缺     

地黄类方药联合间充质干细胞治疗缺血性脑卒中的作用机制

背景：地黄类方药具有抑制氧化应激反应、抑制细胞凋亡、抑制神经炎症、促进血管神经新生、抗衰老的作用,在治疗缺血性脑卒中方面具有独特的优势。以间充质干细胞为载体与地黄类方药联合,可以更好地发挥其治疗缺血性脑卒中的作用。目的：对地黄类方药联合间充质干细胞治疗缺血性脑卒中的作用机制作一综述。方法：检索中国知网和PubMed数据库2012-2022年关于地黄类方药联合间充质干细胞治疗缺血性脑卒中的文献,以“地黄、间充质干细胞、缺血性脑卒中”为中文检索词,以“Rehmannia,mesenchymal stem cells (MSCs),ischemic stroke”为英文检索词,最终共纳入86篇文献进行分析。结果与结论：(1)文章梳理了间充质干细胞治疗缺血性脑卒中的作用机制,主要包括促进细胞迁移、促进细胞分化、免疫调节和抑制细胞凋亡等;(2)文章梳理了地黄类方药治疗缺血性脑卒中的作用机制,主要包括抑制氧化应激、抑制神经炎症、抑制细胞凋亡、促进神经血管新生和抗衰老等作用;(3)文章总结了地黄类方药可以激发间充质干细胞的活力,促进间充质干细胞的增殖,诱导间充质干细胞向神经样细胞方向分化,提高间充质...     

治疗脑出血的干细胞种类研究进展

<正>脑卒中是世界范围内重要致死和致残因素,特别是发达国家,年发病率在0.25%~0.40%,90%的幸存者会落下各种类型的残疾,成为一个沉重的社会和经济负担[1]。脑卒中主要分为2种,缺血性脑卒中和出血性脑卒中,其中出血性脑卒中致死致残率最高。出血性脑卒中又分为脑出血(intracerebral hemorrhage,ICH)和蛛网膜下出血(subrachanoid hemorrhage,     

对氧磷酶2基因C311S多态性与2型糖尿病合并缺血性脑卒中的相关性

目的 探讨对氧磷酶2(paraoxonase 2，PON2)基因多态性与2型糖尿病(type 2 diabetes mellitus，T2DM)患者合并缺血性脑卒中(ischemic stroke，IS)的关系。方法 用聚合酶链反应—限制性片段长度多态性分析法探查PON2基因C311S多态性在T2DM合并IS组、T2DM无IS组以及正常对照组的基因频率。结果 发现中国人存在PON2基因C311S多态性，C／S等位基因频率为0．145／0．855。T2DM合并IS组患者PON2基因的C等位基因频率显著高于T2DM无IS组和正常对照组，差异有显著性(P＜0．05)。结论 中国人2型糖尿病患者PON2基因第311位密码子的多态性与并发缺血性脑卒中有关，C等位基因是2型糖尿病并发缺血性脑卒中的危险因素之一。     

缺血性脑卒中患者血清胆红素和血脂的变化研究

目的探讨缺血性脑卒中患者血清胆红素和血脂的变化。方法142例缺血性脑卒中患者(研究组)和105例健康体检的非缺血性脑卒中患者(对照组)血清胆红素和血脂的水平。结果缺血性脑卒中患者血清TBIL、DBIL显著低于对照组(<0.05);缺血性脑卒中患者血清TC和LDL-C水平显著高于健康对照组(P<0.05)。缺血性脑卒中患者血清TG和HDL-C与对照组比较,差异无统计学意义(>0.05)。结论血清胆红素水平降低、血清TC和LDL-C水平升高是缺血性脑卒中的重要危险因素。     

星形胶质细胞调节缺血性脑卒中的胶质瘢痕形成

背景：缺血性脑卒中是临床上主要的致死及致残性疾病之一，经血管再通获益的患者数量极其有限，故探索有效治疗手段迫在眉睫。以星形胶质细胞为主所形成的胶质瘢痕作为缺血性脑卒中的重要病理变化之一，是阻碍脑卒中后期轴突再生和神经修复的主要原因。目的：通过对缺血性脑卒中后星形胶质细胞瘢痕形成的病理过程、关键的信号调节机制和潜在治疗靶点进行分析，旨在为干预星形胶质细胞瘢痕形成以有效治疗缺血性脑卒中提供理论依据，并为促进脑卒中后康复提供新策略。方法：全面检索2010-2022年在中国知网、Pub Med和Web of Science数据库收录的相关文献，中文检索词：“缺血性脑卒中、脑缺血、星形胶质细胞、胶质瘢痕、胶质增生、星形胶质细胞增多症”，英文检索词：“Ischemic stroke,Brain ischemi*,Cerebral ischemi*,Astrocyt*,Astroglia*,Glial scar,Gliosis,Astrogliosis”，经筛选后纳入78篇文献进行综述。结果与结论：(1)星形胶质细胞在中枢神经系统稳态的维持中具有重要作用，缺血性脑卒中发生后，星形胶质细胞从静息态转变...     

丁苯酞辅助治疗对急性缺血性脑卒中血液流变学及神经保护作用分析

目的:探究丁苯酞辅助治疗对急性缺血性脑卒中血液流变学及神经保护作用.方法:选取本院 2020年 12 月至 2023 年 7 月收治的急性缺血性脑卒中患者 87 例,根据治疗方案不同分为对照组 42 例(常规治疗)和观察组45 例(丁苯酞辅助治疗).观察并比较两组临床疗效、血液流变学指标、神经功能状态(美国国立卫生院量表(National Institute of Health stroke scale,NIHSS)、改良型Rankin量表(Modified Rankin Scale,mRS))和不良反应.结果:观察组总有效率明显高于对照组(P＜0.05);治疗后两组各血液流变学指标值、NIHSS评分、mRS评分均明显下降,且观察组各指标值均低于对照组(P＜0.05);两组均未见严重不良反应.结论:丁苯酞辅助治疗可有效改善急性缺血性脑卒中患者血液流变学,并促进神经功能恢复,其临床疗效显著,安全性较好.     

脑缺血再灌注模型大鼠接受跑台运动锻炼海马反义导向分子A的表达

背景：脑卒中后,运动锻炼对其神经功能的康复具有极其重要的作用,但关于卒中后大鼠运动量的研究鲜有报道。而海马与认知功能密切相关,但大鼠缺血再灌注后海马内反义导向分子A的表达的研究,国内外未见报道。 目的：探索运动锻炼对脑缺血再灌注后大鼠缺血侧海马内反义导向分子A表达的影响。 方法：将120只SD大鼠随机等分为正常组、假手术组、模型7,14,28 d组,模型7,14,28 d组大鼠采用线栓法制作大鼠右侧脑缺血再灌注模型。各组大鼠各等分为`4个亚组：非运动亚组、低、中、高运动量亚组。低运动量组进行5 m/min,5 min;7 m/min,5 min;9 m/min,20 min跑台训练;中运动量组进行8 m/min,5 min;10 m/min,5 min;13 m/min,20 min跑台训练;高运动量组进行8 m/min,5 min;11 m/min,5 min;20 m/min,20 min跑台训练。 结果与结论：非运动时,模型7 d组大鼠缺血侧海马反义导向分子A mRNA和蛋白表达水平最高,且反义导向分子A相对表达水平随时间延长而逐渐降低。与非运动相比,模型14,28 d组大鼠中运动量时缺血侧海马反义导向分子A mRNA和蛋白表达水平明显下降(P < 0.05),而高运动量海马反义导向分子A mRNA和蛋白表达水平表达增加。提示中运动量锻炼可以降低脑缺血再灌注大鼠患侧海马反义导向分子A的表达。 中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程全文链接：     

人参皂苷Rb1对大鼠脑缺血再灌注损伤中NAIP表达的影响

目的:观察人参皂苷Rb1对神经元凋亡抑制蛋白(neuronal apoptosis inhibitory protein,NAIP)在脑缺血再灌注损伤中表达的影响,探讨人参皂苷Rb1对缺血性脑病的防治机制.方法:线栓法阻断大鼠大脑中动脉2 h,再灌注3 h～5 d制备脑缺血再灌注模型,应用免疫组织化学方法标记NAIP阳性细胞,观察人参皂苷Rb1对NAIP阳性细胞数的影响.结果:缺血再灌注后,缺血半暗带内的NAIP阳性细胞表达增加,海马CA 1区等部位的NAIP阳性细胞数量也明显增加,而缺血中心区无NAIP阳性细胞的表达.实验对照组中NAIP阳性细胞数量随再灌注时间延长逐渐升高,12 h达到高峰,至5 d时NAIP阳性细胞数量表达低于正常水平.实验用药组中NAIP阳性细胞数量在2 d时达到高峰,且其高峰值明显高于实验对照组中的高峰值,后随再灌注时间的延长而逐渐下降,至5 d时仍处于较高水平.结论:脑缺血再灌注后,NAIP表达增加是脑组织对损伤的一种保护性反应,其对缺血区周围的神经细胞的保护作用更为明显.NAIP在脑组织中的表达具有一定的时间规律性,并且人参皂苷Rb1可能通过上调NAIP的表达发挥对受损脑组织的保护作用.     

川芎嗪对大鼠脑缺血再灌注损伤后GFAP表达和脑组织水肿的影响

探讨川芎嗪对大鼠脑缺血再灌注损伤后星形胶质细胞表达胶质原纤维酸性蛋白(GFAP)以及对脑组织含水量的影响。将70只SD大鼠随机分为3组:脑缺血后1、3、5、7、10d模型组(n=30,每个时间点用6只)、川芎嗪预处理组(n=30,每个时间点用6只)和假手术组(n=10,每个时间点用2只)。采用线栓法制作大鼠局灶性脑缺血再灌注模型(MCAO),应用免疫组化法观察星形胶质细胞GFAP的表达,干湿重法测定脑组织的含水量。结果显示:川芎嗪预处理组大鼠各时间点海马CA1区的GFAP阳性细胞数量显著增多,与缺血模型组比较均有显著性差异(P<0.05)。缺血再灌注后脑组织含水量持续性增加,到3d达到最高峰,5d时仍较高,以后逐渐降低;川芎嗪组各时间点的脑组织含水量均低于缺血模型组(P<0.05)。上述研究结果提示川芎嗪可引起星形胶质细胞活化、保护神经元、减轻脑水肿,具有防治脑缺血再灌注损伤的作用。     

小胶质细胞在脑缺血再灌注损伤中的作用

炎症反应在脑缺血再灌注损伤机制中十分重要,而脑内小胶质细胞的激活是炎症反应中的重要环节.在脑缺血再灌注损伤过程中,小胶质细胞被激活,并对神经细胞发挥了损伤与保护双重作用.小胶质细胞对脑缺血再灌注损伤机制作用的复杂性,使其在脑缺血再灌注损伤研究中的意义也越来越受到重视.研究从小胶质细胞在脑缺血再灌注损伤后被激活参与炎症反应,与活化的小胶质细胞自身对脑缺血再灌注损伤的作用对小胶质细胞在脑缺血再灌注损伤中的双重作用很有意义.     

Protection by silibinin against experimental ischemic stroke: Up-regulated pAkt,pmTOR, HIF-1α and Bcl-2, down-regulated Bax,NF-κB expression

Inflammation and apoptosis play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Silibinin has been proved to elicit a variety of biological effects through its anti-inflammatory and anti-apoptotic properties in hepatotoxic, cancer and carcinogenic events. Whether this protective effect applies to ischemic injury in brain is still unknown, we therefore investigated the potential protective role of silibinin in ischemic stroke and the underlying mechanisms. Silibinin was administered intragastric 30 min before permanent middle cerebral artery occlusion (pMCAO). We found that silibinin significantly alleviated neurological deficit, reduced infarct volume, and suppressed brain edema, which were accompanied with upregulation of pAkt, pmTOR, HIF-1α, Bcl-2 and downregulation of Bax, NF-κB in ischemic brain tissue after stroke. Our results show that silibinin might exert anti-inflammatory and anti-apoptotic effects in ischemic brain through activating Akt/mTOR signaling.     

Coupling between neuronal nitric oxide synthase and glutamate receptor 6-mediated c-Jun N-terminal kinase signaling pathway via S-nitrosylation contributes to ischemia neuronal death

S-nitrosylation, as a post-translational protein modification, recently has been paid more and more attention in stroke research. S-nitrosylation regulates protein function by the mechanisms of covalent attachment that control the addition or the removal of nitric oxide (NO) from a cysteine thiol. The derivation of NO is established by the demonstration that, in cerebral neurons, NO mainly generates from neuronal nitric oxide synthase (nNOS) during the early stages of reperfusion. In the past researches, we demonstrate that global ischemia-reperfusion facilitates the activation of glutamate receptor 6 (GluR6) -mediated c-Jun N-terminal kinase (JNK) signaling pathway. The objective of this study is primarily to determine, during the early stages of reperfusion in rat four-vessel occlusion (4-VO) ischemic model, whether nNOS-derived NO affects the GluR6-mediated JNK signaling route via S-nitrosylation which is performed mainly by the biotin switch assay. Here, we show that administration of 7-nitroindazole, an inhibitor of nNOS, or ketamine, an antagonist of N-methyl-d-aspartate receptor (NMDAR), diminishes the increased S-nitrosylation of GluR6 induced by cerebral ischemia-reperfusion. In contrast, 2-amion-5,6-dihydro-6-methyl-4H-1,3-thiazine, an inhibitor of inducible NO synthase does not affect S-nitrosylation of GluR6. Moreover, treatment with sodium nitroprusside (SNP), an exogenous NO donor, increases the S-nitrosylation and phosphorylation of nNOS, leading to the attenuation of the increased S-nitrosylation of GluR6 and the assembling of GluR6* postsynaptic density protein 95 (PSD95)* mixed lineage kinase 3 (MLK3) signaling module induced by cerebral ischemia-reperfusion. The results also show that GluR6 downstream MLK3* mitogen activated protein kinase kinase 4/7* JNK signaling module and nuclear or non-nuclear apoptosis pathways are involved in the above signaling route. However, dithiothreitol (DTT) antagonizes the neuroprotection of SNP. Treatment with DTT alone, as a negative control, prevents S-nitrosylation of proteins, which indicates the existence of endogenously produced S-nitrosylation. These data suggest that GluR6 is S-nitrosylated by endogenous NO in cerebral ischemia-reperfusion, which is possibly correlated with NMDAR* PSD95* nNOS signaling module, and further activates GluR6* PSD95* MLK3 signaling module and JNK signaling pathway. In contrast, exogenous NO donor antagonizes the above action of endogenous NO generated from nNOS. Thus, our results provide the coupling of nNOS with GluR6 by S-nitrosylation during the early stages of ischemia-reperfusion, which can be a new approach for stroke therapy.     

脑缺血再灌注动物模型的血脑屏障损伤*☆

背景：脑缺血再灌注后血脑屏障遭到破坏,引起脑水肿和脑出血,组织损伤程度加重。 目的：总结分析脑缺血再灌注动物模型血脑屏障相关分子,在脑缺血再灌注后血脑屏障损伤中的作用。 方法：以“Cerebral ischemia-reperfusion injury, blood brain barrier permeability,”为检索词,检索近十年PubMed数据库,文献检索语种限制为英文。以“脑缺血再灌注,血脑屏障”为检索词,检索5年内中国期刊全文数据库,文献检索语种限制为中文。纳入与脑缺血再灌注及血脑屏障损伤密切相关的研究;排除重复性研究。选取17篇总结分析。 结果与结论：从炎症因子的浸润,基质金属蛋白酶的水解以及水通道蛋白的开放等方面总结脑缺血再灌注损伤后血脑屏障相关分子,提出多因素多环节调控血脑屏障功能。CIR后血脑屏障开放的3 h时间窗为急性期抢救缺血半暗带关键点,基质金属蛋白酶的后期修复作用也可为新药研发提供依据。      

The anti-inflammatory effects of D-allose contribute to attenuation of cerebral ischemia-reperfusion injury

It has been proved that multiple independently lethal mechanisms are involved in cerebral ischemia-reperfusion injury. Inflammatory processes, mediated by activated leukocytes, have been implicated in the mechanisms of cerebral ischemia-reperfusion injury. In addition, the leukocytes accumulated in the perivascular areas during the inflammatory responses after reperfusion will transform oxygen to reactive free radicals, release cytotoxic products and vasoactive substances, which further promotes brain injury. So activated leukocytes play an important role in the pathophysiologic process of cerebral I/R injury. D-allose, a rare sugar produced from D-ribose, attracts increased attention from researchers in recent years. It has been proved that D-allose can produce inhibitory effects on activated leukocytes in liver, kidney and retina, including immunosuppressive effects, anti-inflammatory effects, as well as anti-oxyradical effects. Furthermore, recent research work of our colleagues has demonstrated that D-allose could attenuate cerebral I/R injury by anti-oxyradical effects. However, inflammatory responses play an important role in the mechanisms of cerebral I/R injury. So we hypothesize that D-allose might perform neuroprotection against cerebral ischemia-reperfusion injury by its anti-inflammatory effects.     

Neuroprotective potential of Piroxicam in cerebral ischemia: An in silico evaluation of the hypothesis to explore its therapeutic efficacy by inhibition of aquaporin-4 and acid sensing ion channel1a

Cerebral stroke is caused by acute interruption of the brain arterial blood supply and is one of the major health problems with no effective treatments so far apart from the thrombolytic recombinant tissue plasminogen activator (rt-PA), which must be administered within 3h of stroke onset. This emerges it as the third leading cause of mortality worldwide. Acidosis and brain edema are the prominent metabolic features of ischemic brain. The combined inhibition of aquaporin-4 (AQP4) and ASIC1a channels may offers a new neuroprotective approach in cerebral stroke management. Moreover, the combined inhibition of AQP4 and ASIC1a with NSAID remains unknown against neuroprotection in animal models of cerebral ischemia. NSAIDs are believed to act as a pharmacological molecule that reported to have an antioxidant and anti-inflammatory properties. Therefore, the target of the present in silico study was to determine the neuroprotective efficacy of Piroxicam, a NSAID in animal model of cerebral ischemia/reperfusion (I/R) injury and efforts were made to analyze its inhibitory effects on aquaporin-4 activation and ASIC1a channels mediated downstream survival/damage mechanisms. Thus we hypothesized that Piroxicam, a NSAID can act as a neuroprotective agent in animal model of cerebral ischemia/reperfusion (I/R) injury due to its inhibitory effects on aquaporin-4 channel and ASIC1a channels. It is indeed vital that we do not give up the fight to develop compounds to treat stroke despite the many years of setbacks. One of the mottos of our proposed hypothesis is to find out a successful modality of effective substantial treatment of brain stroke with other anti stroke therapeutics available till date.