This study aimed to investigate the inhibitory effect and mechanism of Cucurbitacin I (Cu I) on apoptosis, oxidative stress, and mitophagy in PC12 cells with glucose and oxygen deprivation/reperfusion (OGD/RP) injury. OGD/RP cell injury model was established by gas anoxic cell incubator and glucose-free medium. The cells were divided into the control group, OGD/RP group, OGD/RP + Cu I group, and OGD/RP + Cu I + 2 µM nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor ML385 group. The results showed that apoptotic rate and reactive oxygen species (ROS) production were significantly increased in OGD/RP group, which were reversed by Cu I pretreatment. Meanwhile, western blot analysis proved that Cu I inhibited OGD/RP-induced mitophagy, manifested as the decreased expression of PTEN-induced kinase 1 (PINK1) and parkin RBR E3 ubiquitin-protein ligase (Parkin), and light chain 3 (LC3) Ⅱ∕LC3 I, as well as the increased expression of P62. Furthermore, immunofluorescence (IF) staining showed that Cu I reduced the co-localized puncta of LC3 with TOM20 in OGD/RP-induced PC12 cells. Similarly, transmission electron microscope finding is consistent with the IF results. Mechanically, after Cu I and OGD/RP treatments, nuclear Nrf2 expression and the levels of downstream target genes were significantly upregulated compared with OGD/RP alone treatment. Nrf2 inhibition reversed the protective effects of Cu I on OGD/RP-induced injury in PC12 cells. The present study provides evidence of the neuroprotective effect of Cu I unraveling its potential as a potential therapeutic candidate for the treatment of ischemic stroke. Keywords Cucurbitacin I , cerebral ischemia , PC12 cells , oxidative stress , mitophagy
目的 探讨干扰SOX6基因表达对H2O2诱导的星形胶质细胞(AS)凋亡、线粒体膜电位及PI3K/AKT信号通路影响.方法 从乳大鼠大脑皮质分离培养AS细胞,将细胞分为阴性对照组(NC组):AS转染无干扰作用的siRNA;H2 O2组:20μmol/L的H2O2处理AS细胞24 h;H2O2+NC组:无干扰作用的siRNA转染AS细胞24 h后,20μmol/L的H2O2处理细胞24 h;H2O2+si-SOX6组:SOX6特异性siRNA转染AS细胞24 h后,20μmol/L的H2O2处理细胞24 h.通过LDH试剂盒、流式细胞术及JC-1探针分别检测细胞毒性、凋亡率及线粒体膜电位;Western blotting检测SOX6、Cyt.C、caspase3、caspase9、Bcl-2、Bax和p-AKT蛋白表达.结果 H2O2可明显上调AS细胞SOX6、Cyt.C、caspase3、caspase9和Bax表达,下调Bcl-2和p-AKT表达,提高细胞毒性,诱导细胞凋亡,而干扰SOX6基因表达可明显减弱H2O2对细胞SOX6、Cyt.C、caspase3、caspase9、Bcl-2、Bax和p-AKT表达及细胞毒性和凋亡影响.结论 干扰SOX6基因表达可通过抗凋亡途径保护H2O2诱导的AS损伤,此保护作用与线粒体通路及PI3K/AKT信号通化激活有关.
目的:探讨敲减IQGAP1基因表达对脑胶质瘤细胞侵袭、迁移及免疫抑制的影响及机制。方法:将人脑胶质瘤U251细胞随机分为空白组、阴性对照组和si-IQGAP1组,AG490作为STAT3信号通路抑制剂。转染48 h后,MTT法检测细胞活力;Western blot检测IQGAP1、血管内皮生长因子(VEGF)、转化生长因子β1(TGF-β1)、STAT3和p-STAT3的蛋白水平;Transwell小室检测细胞的侵袭和迁移能力。结果:si-IQGAP1-1组和si-IQGAP1-2组的IQGAP1蛋白表达均显著低于空白组(P<0.05)。与空白组比较,si-IQGAP1组和AG490组的细胞活力、侵袭能力和迁移能力均显著降低,VEGF、TGF-β1和p-STAT3的蛋白水平均显著降低(P<0.05)。与AG490组比较,AG490+si-IQGAP1组的细胞活力、侵袭能力和迁移能力均显著降低,VEGF和TGF-β1的蛋白表达均显著降低(P<0.05)。结论:敲减IQGAP1基因表达可降低脑胶质瘤细胞的侵袭和迁移能力,减弱细胞免疫抑制因子VEGF和TGF-β1的表达,机制与下调STAT3信号通路有关。
目的:检测高原环境(海拔4 500m)大鼠脑损伤周围局部组织内不同时间点TNF-α和IL-1β蛋白的表达及动态变化;同期与西宁地区(海拔2 200m)大鼠脑损伤周围局部组织各对应时间点相同因子蛋白表达比较,探讨高原环境对大鼠脑损伤局部炎性反应的影响.方法:将健康SD雄性大鼠60只平均、随机分为高原环境组和西宁地区组.每组随机抽取25只建立大鼠创伤性颅脑损伤模型(造模组),各组剩余5只单纯暴露硬膜不打击(对照组).颅脑损伤后第1天、3天、5天、7天、14天应用酶联免疫吸附法检测各组脑损伤大鼠周围组织内TNF-α和IL-1β蛋白含量及变化.结果:高原环境造模组TNF-α、IL-1β第1天、3天、5天、7天、14天表达均比西宁地区造模组同时间点增加,差异有统计学意义(P<0.05),第14天高原环境造模组TNF-α、IL-1β含量未完全恢复至对照组水平,差异有统计学意义(P<0.05).结论:高原环境加重了大鼠脑损伤周围局部组织的炎性反应且消退缓慢.
OBJECTIVETo analyze the clinical characteristics of 24 patients with cysticercosis of the fourth ventricle, and to evaluate the therapeutic efficacy of microsurgery.METHODSThe clinical data of 24 patients with cysticercosis of the fourth ventricle referred the Department of Neurosurgery of the Affiliated Hospital of Qinghai University from January 2000 to December 2018 were collected, and the clinical features, imaging characteristics, surgical methods, therapeutic efficacy and postoperative complications were analyzed.RESULTSThe 24 patients included 15 men and 9 women, and had a mean age of 43.5 years (range, 16 to 68 years). Preoperative imaging examinations showed obvious dilatation of bilateral lateral ventricles, the third ventricle and middle cerebral aqueduct, and spherical or cystic dilatation of the fourth ventricle. There were 18 cases positive for antibodies against cysticercus, and 3 of the 21 cases were egg positives. All 24 cases received microsurgery, including 8 cases via the median aperture approach, 7 cases via the median aperture-cerebellar vermis approach, and 9 cases via the transcerebellomedullary fissure approach. There were 17 cases with complete delivery of vesicles, 5 cases with vesicle rupture and 2 cases with extraction of cystic fluid followed by separation and removal of cystic wall. All cases had obvious retraction of the ventricular system and disappearance of intracranial hypertension following surgery. There were 19 cases (79.17%) with well recovery, and 5 cases (20.83%) with aggravation or development of cerebellar ataxia, which recovered following treatment for 1 to 2 weeks.CONCLUSIONSThe transcerebellomedullary fissure approach is a safe and lowly invasive approach for the treatment of cysticercosis of the fourth ventricle.
颅脑创伤是临床常见的多发病,高原地区具有高海拔、低氧、低气压、低温等特点,为了适应高原环境的低氧特点,长时间在高原地区生活,大脑在发育过程中需要在功能与结构上都进行改变,因此颅脑损伤后患者的病理生理也较之前发生改变.高原颅脑损伤模型的建立作为颅脑损伤研究的基础,是研究颅脑损伤的关键.文章旨在对高原环境下颅脑损伤模拟方法和各种颅脑损伤模型的建立方法及特点进行综述,以期为临床提供参考价值.
目的:研究微小RNA-422a (miR-422a)靶向调控人性别决定区Y框6(SOX6)对过氧化氢(H 2 O 2 )刺激下大鼠肾上腺嗜铬细胞瘤细胞株PC12(具有神经细胞特性)损伤的作用。方法:采用real-time PCR检测H 2 O 2 处理后PC12细胞中miR-422a表达的变化,在PC12细胞中转染miR-422a mimics,MTT法测定细胞活力,试剂盒检测乳酸脱氢酶(LDH)漏出率,流式细胞术测定细胞凋亡水平。靶基因预测软件预测SOX6可能是miR-422a的靶基因,萤光素酶报告基因实验鉴定靶向关系。在PC12细胞中共转染miR-422a mimics和SOX6过表达载体,检测过表达SOX6对miR-422a mimics调控H 2 O 2 条件下PC12细胞活力、LDH漏出率和凋亡的影响。结果:H 2 O 2 处理后PC12细胞中miR-422a表达水平降低(P<0.05)。H 2 O 2 处理后的PC12细胞的活力降低,LDH漏出率和细胞凋亡率升高(P<0.05)。miR-422a mimics能够提高H 2 O 2 条件下PC12细胞活力,降低LDH漏出率和凋亡率(P<0.05)。miR-422a靶向负调控SOX6表达。SOX6过表达载体可以逆转miR-422a对PC12细胞活力提高和LDH漏出率、细胞凋亡率降低的作用(P<0.05)。结论:miR-422a通过靶向抑制SOX6可降低H 2 O 2 对PC12细胞的损伤作用。
目的:探讨高原高血压脑基底节区出血经侧裂入路手术联合高压氧治疗的临床效果.方法:将经侧裂入路手术后常规应用脑细胞活化剂、止血、支持治疗并早期高压氧治疗的36例患者作为治疗组,选取较前普通照明下开颅经颞叶血肿清除常规治疗36例患者作为对照组.比较两组临床疗效、并发症的发生率.结果:治疗组有效率88.8%明显高于对照组66.6%;术后随访半年,两组患者共存活68例、死亡4例,其中治疗组死亡1例,对照组死亡3例.死亡4例中再出血1例放弃再次手术,脑功能衰竭2例,肾功能衰竭1例.结论:经侧裂入路手术清除脑基底节出血是一种安全有效的治疗方法,术后早期采用高压氧治疗可有效改善微循环,抗缺氧,保护脑细胞,降低致残率,疗效显著.
脑室-腹腔分流术是治疗脑积水最常用的方法.以往分流管腹腔端的放置需开腹后置入.近年来越来越多的分流手术采用腹腔镜放置分流管腹腔端,放置简单,位置准确,术后并发症减少等优点.手术中应用腹腔镜在腹腔中微创置管治疗脑积水15例,手术过程简单、安全,术野清晰,手术疗效良好,现报告如下.
后颅窝硬膜外血肿是常见的颅脑损伤疾病,血肿往往继发于枕骨骨折以及横窦损伤[1-2].采用枕部开窗清除后颅窝硬膜外血肿,较以往采用枕下旁正中直切口,手术方法简便易行,避开颈部分离肌肉过程,开颅速度快,在冷光源辅助下能够彻底清除血肿.手术疗效好,现报告如下. 一、对象与方法 1.一般资料:本文资料根据我院2013年1月至2016年12月外伤致后颅窝硬膜外血肿病例15例.其中男11例,女4例.年龄8~72岁,平均45.4岁.术前Glasgow评分:8~12分10例,12分以上5例.跌落8例,车祸2例,打击3例,其他2例.
目的 通过检测颅脑损伤(TBI)患者入院后不同时间段血清中的Tau蛋白浓度,对照比较TBI患者标准化治疗后的预后情况.方法 筛选无TBI及相关颅脑疾病的体检者为对照组,检测对照组血清中Tau蛋白的浓度.收集临床确诊的TBI患者76例,于伤后的6 h及1、3、7 d分别采集患者血清标本.通过ELISA法分别检测对应时间段内的血清Tau蛋白浓度.于患者入院标准化治疗1个月后进行随访或复诊计算患者预后分数(通过Barthel指数评分计算).应用SPSS统计软件对患者血清中Tau浓度、GCS评分、Barthel指数评分进行相关性分析.结果 各TBI组血清Tau蛋白浓度与对照组相比较,差异有统计学意义(P<0.05);重型组与轻中型组相比较,其血清Tau蛋白浓度差异有统计学意义(P<0.05).重型组患者的预后明显差于轻中型组.预后不同的各组血清中Tau蛋白浓度相比较,预后差组、预后中组、预后良组与对照组差异有统计学意义(P<0.05);预后差组与预后中组、预后良组差异有统计学意义(P<0.05);预后中组与预后良组差异无统计学意义(P>0.05).结论在发生TBI后,患者血清中Tau蛋白含量升高,升高的程度与TBI的严重程度呈正相关.TBI的程度与患者预后有关,损伤越重,患者预后越差.预后差患者与患者血清中Tau蛋白含量相关,Tau蛋白含量极高者预后差.
Objective To explore the change in endocrine hormone in the patients with severe traumatic brain injury in the plateau. Methods The serum levels of FSH, LH and PRL were determined by quantitative radioimmunoassay method in 60 patients with severe traumatic brain injury and 60 patients with mild traumatic brain injury 1, 3, 7, 14 and 21 days after the injury and were statistically analyzed. Results There were insignificant differences in the serum levels of FSH and LH between the patients with severe traumatic brain injury and the patients with mild traumatic brain injury 1, 3, 7, 14 and 21 days after the injury (P>0.05). The serum levels of PRL were significantly higher in the patients with severe brain injury than that in the patients with mild brain injury 1 day after the injury (P<0.05). Conclusions The serum level of PRL may be increased 1 day after the injury in the patients with severe traumatic brain injury compared to that in the patients with mild traumatic brain injury. But there were insignificant changes in the serum levels of FSH and LH in the patients with severe brain injury compared to that the patients with mild brain injury 1, 3, 7, 14 and 21 days after the injury.
Objective:To explore water dissection technique of Toth for the treatment of hypertensive basal ganglia hematoma.Method:From June 2009 to December 2013, 42 patients with hypertensive basal ganglia hematoma underwent surgery management via transsylvian fissure approach by water dissection technique of Toth, the therapeutic effect of the management was analyzed retrospectively.Result:Postoperative CT showed that the total evacuation of hematomas was reached in 28 patients, subtotal evacuation in 10 patients and greatly part in 4. 42 patients were followed up and evaluated by Glasgow outcome scale for at least 3 months. Among them, 14 patients showed good recovery, 12 patients showed moderate disability, 7 patients showed severe disability, 2 patients died.Conclusion:It is safe, effective and minimally invasive for the treatment of hypertensive basal ganglia hematoma via transsylvian fissure approach by water dissection technique of Toth.
目的 探讨切除蝶-岩斜区肿瘤的最佳手术方法、经验和技巧,以提高手术全切率与改善预后.方法 回顾性分析显微手术治疗的36例蝶-岩斜区肿瘤的临床资料,其中脑膜瘤24例,神经鞘瘤8例,表皮样囊肿4例.采用颞枕经小脑幕-经岩嵴入路19例、乙状窦前入路15例、乙状窦后入路2例.结果 肿瘤全切29例(29/36,80.56%),次全切除7例(7/36,19.44%),无手术死亡病例.其中,乙状窦前人路15例,术后出现面瘫3例、听力下降2例、局部脑脊液滞留3例、脑脊液外漏合并感染1例.结论 采用颞枕经小脑幕-经岩嵴入路切除蝶-岩斜区肿瘤,有利于降低脑神经损伤、减少脑脊液漏的发生率,是目前治疗此类肿瘤的最佳手术方法.
<正>患者,女性,45岁。脑积水术后6年,间断性咳血性痰半年入院。患者6年前曾因突发头痛伴呕吐住院治疗,确诊为病毒性脑炎,治愈后出院。3个月后出现头晕、进行性双下肢无力伴行走摇晃。无意识障碍。外院CT提示交通性脑积水,并行脑室-腹腔分流术,症状缓解后出院。期间患者病情平稳。半年前出现刺激性咳嗽、且痰中带少量新鲜血液。行胸部X线片及CT提示:分流管入腹腔段返折突入胸腔嵌入肺组织,无液气胸(图1)。
目的:探讨醒脑静注射液治疗高血压脑基底节出血选择性小骨窗微创手术后的临床效果。方法:将小骨窗微创手术后采用常规应用脑细胞活化剂,止血、支持治疗的36例患者作为对照组,治疗组在此基础上采用中药制剂醒脑静,静点治疗。比较两组临床疗效、并发症的发生率。结果:治疗组有效率91.67%明显高于对照组63.89%;术后随访半年,治疗组死亡1例,对照组死亡3例。死亡4例中再出血1例放弃再次手术,脑功能衰竭2例,反复消化道出血1例。结论:小骨窗微创清除脑内血肿是一种安全有效的治疗方法,术后采用中西医结合治疗可有效改善微循环,抗缺氧,保护脑细胞,疗效显著。
例l,患者,女性,21岁,以“间断性头痛2个月,伴左眼视力进行性下降”为主诉人院.查体:神志清楚,问答切题.左眼瞳孔不规则、直径约O,35 cm,直接光感迟、间接光感灵敏,右眼瞳孔圆形、直径约0.3 cm,直接、间接光反射灵敏.
目的:分析丹红注射液治疗外伤性脑梗死的疗效。方法:将50例患者随机分为两组,每组25例,治疗组(25例)在常规治疗的基础上给予丹红注射液30mL静脉滴注,对照组给予丹参30mL静滴治疗观察。治疗前后比较两组患者临床疗效及神经功能缺损的变化。结果:治疗组症状体征变化改善明显优于对照组,且治疗组与对照组比较有显著差异(P<0.01)。结论:丹红注射液治疗外伤性脑梗塞较丹参效果明显。
颅骨骨内脂肪瘤是一种极为罕见的良性肿瘤.头颅CT(尤其是CT值的测定)或MRI所显示的脂肪成分可作出定性诊断和鉴别诊断.手术切除可达到治愈的目的.
钻孔冲洗引流术是目前治疗慢性硬膜下血肿的最佳治疗方法,但难治性及易复发性慢性硬膜下血肿需开颅手术治疗.我科自2005年10月至2010年5月共收治16例难治性及易复发性慢性硬膜下血肿患者,进行开颅手术治疗,取得满意的效果,现报告如下.