丁酸钠促脑胶质瘤细胞分化作用研究进展

丁酸钠(NaB)是一种短链脂肪酸诱导分化剂,对脑胶质细胞瘤可通过抑制其组蛋白脱乙酰基转移酶,致细胞的基因表达、酶类和信号传导通路发生变化来遏制恶性瘤细胞的增殖,促进分化。同时,与化学疗法或温热疗法联合应用时,可产生协同效应。但由于其血浆中的半衰期较短,使其在临床上的应用受到了一定的影响。丁酸钠将会成为一种有潜力的治疗脑胶质细胞瘤药物。     

Extracellular signal regulated kinases 1/2 signal pathway and responses of astrocytes after diffuse brain injury

BACKGROUND: The treatment of diffuse brain injury during an acute period is focused on relieving degrees of secondary brain injury. Generation and development of pathological changes of secondary brain injury depend on signal conduction, so down-regulating over response of astrocyte through interfering a key link of signal conduction pathway may bring a new thinking for the treatment of diffuse brain injury. OBJECTIVE: To observe the effect of over activity of extracellular signal regulated kinases 1/2 (ERK1/2) signal pathway on the response of astrocyte during an acute period of diffuse brain injury. DESIGN: Completely randomized grouping and controlled animal study. SETTINGS: Department of Neurosurgery, the Third Affiliated Hospital, Nanchang University; Department of Neurosurgery, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology. MATERIALS: A total of 158 healthy male SD rats, of 11 weeks old, weighing 320–370 g, were provided by Experimental Animal Faulty, Tongji Medical College, Huazhong University of Science and Technology. Rabbit-anti-phosphorylated ERK1/2 (pERK1/2) polyclonal antibody was provided by R&D Company; rabbit-anti-glial fibrillary acidic protein (GFAP) polyclonal antibody, SP immunohistochemical kit and horseradish peroxidase (HRP)-labeled goat-anti-rabbit IgG by Santa Cruz Company; specific inhibitor U0126 of ERK1/2 signal pathway by Alexis Company. METHODS: The experiment was carried out in the Laboratory of Neurosurgery, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from September 2004 to March 2006. ① Detection of pERK1/2 expression: A total of 110 rats were randomly divided into sham operation group (n =5), model group (n =35), high-dosage U0126 group (n =35) and low-dosage U0126 group (n =35). Rats in the sham operation group were only treated with incision of epicranium and fixation of backup plate, but not hit. Rats in the model group were used to establish diffuse brain injury models based on Marmarou free falling body without drug intervention. Rats in the high- and low-dosage U0126 groups were injected into caudal vein with 0.1 and 0.05 mg/kg U0126, respectively, and then, rats were hit to establish injured models. Every 5 rats were collected from model, high- and low-dosage U0126 groups at 5, 30 minutes, 3, 12, 24, 72 hours and 7 days after diffuse brain injury to detect pERK1/2 expression in cortex of parietal lobe based on Western blot technique. ② Distribution of pERK1/2 and positive GFAP cells in brain tissue: Another 48 rats were randomly divided into sham operation group (n =3), model group (n =15), high-dosage U0126 group (n =15) and low-dosage U0126 group (n =15). The intervention and administration were dealt as the same as those mentioned above. Every 3 rats were collected from model, high- and low-dosage U0126 groups at 30 minutes, 3, 12, 24 and 72 hours after model establishment to observe the distribution of pERK1/2 and postive GFAP cells in brain tissue which was cut from coronal section at Bregma –4.8 mm layer with immunohistochemical staining. MAIN OUTCOME MEASURES: pERK1/2 expression in cortex of parietal lobe and distribution of pERK1/2 and positive GFAP cells in brain tissues. RESULTS: ① pERK1/2 expression: After diffuse brain injury, pERK1/2 expression in cortex of parietal lobe was rapidly increased in the model group, reached at peak at 5 minutes and then decreased gradually. But the expression was still in a high level until the 72nd hour and fallen to the basic level on the 7th day. pERK1/2 level was lower in high- and low-dosage U0126 groups than that in model group at various time points (P < 0.01); meanwhile, pERK1/2 level was lower in high-dosage U0126 group than that in low-dosage U0126 group. The results showed that there was a certain dosage dependence on pERK1/2 expression. ② Distribution of pERK1/2 and positive GFAP cells in brain tissue: Positive expression of pERK1/2 lasted in brain tissue from 30 minutes to 72 hours after diffuse brain injury (P < 0.05). In addition, from 30 minutes to 3 hours, brown-yellow stained cells were mainly distributed in plasma, but rarely in nucleus. A lot of positive cells had tree-like apophysis, which was similar to neurons. With the time passing by, more and more nuclei manifested positive stains; moreover, nuclei mainly manifested positive staining until 24 hours after diffuse brain injury. Immune-positive pERK1/2 cells were widely distributed in brain tissue, especially mainly in binding site between deep cortex and cerebral white matter, and then in hippocampus. In addition, ependymal cell and vascular endothelial cells of choroids plexus also manifested strongly positive staining. As compared with model group, positive cells were decreased gradually in high- and low-dosage U0126 groups. However, number of positive cells was less in high-dosage U0126 group than that in low-dosage U0126 group. CONCLUSION: Diffuse brain injury strongly induces the activity of ERK1/2 signal pathway and response of astrocyte; in addition, U0126 can inhibit response of glial cells during an acute period, and the effect manifests dosage dependence.     

成人肾外型肾母细胞瘤1例报告

患者,女,27岁.因"左腹部阵发性疼痛7d"入院.查体:神志清,精神不振,营养发育正常,皮肤粘膜无黄染,浅表淋巴结无肿大.心肺无异常.腹平软,肝脾未及,左上腹可扪及一约7cm×5cm大小肿块,质硬,活动度差.     

儿童肾母细胞瘤的CT诊断

目的：探讨CT对儿童肾母细胞瘤的诊断价值。方法：回顾分析22例经手术病理证实为肾母细胞瘤的CT表现特点。结果：21例肾母细胞瘤位于单侧肾脏，位于上极14例，下极7例，表现为强化不明显的实质性肿块，瘤内常见坏死，出血与囊性病变，极少钙化，典型表现为残存肾实质呈“新月形”强化。结论：CT检查可清晰显示原发肿瘤及其侵犯,主时发现腹膜后淋巴结转移，对肾原发肿瘤与腹膜后肾外肿瘤的鉴别诊断有重要价值。     

巨大脊髓圆锥血管母细胞瘤一例并文献复习

目的 探讨脊髓血管母细胞瘤的诊断、治疗及预后.方法 对1例圆锥部位巨大血管母细胞瘤的诊治进行报告,并结合文献对脊髓血管母细胞瘤进行回顾分析.结果 脊髓血管母细胞瘤可以是单独发生,也可以是Von Hippel-Lindau病的系列疾病之一,临床发病率低,最常见症状是疼痛,MRI表现为瘤结节明显强化,周围可见异常血管流空影,多伴有空洞,DSA可显示染色的瘤结节、供血动脉及引流静脉,显微神经外科手术可完整全切.结论 显微神经外科手术是治疗脊髓血管母细胞瘤的最佳方法.对于有症状患者,应尽早手术,无症状患者可以定期复查MRI,如表现为肿物生长,可视为手术指证,患者预后较好.     

工频磁场对星形胶质细胞间隙连接通讯功能的影响

目的　探讨工频磁场 (PFMF)是否有促癌或协同促癌作用。方法　利用荧光光漂白后再恢复法观察漂白细胞荧光强度的恢复以判断经间隙连接的细胞间通讯 ,以相对荧光强度恢复速率(CFIRR)作为对细胞间隙连接通讯 (GJIC)作用的评价指标 ,研究不同磁场强度单独作用或协同佛波酯(TPA)对星形胶质细胞GJIC功能的影响。结果　 3ng/mlTPA作用 1h时CFIRR的中位数 (Md)值为4 .53 % /min ,空白对照组为 9.74% /min ,两组的差异有显著性 (H =1 2 .0 84,P <0 .0 0 5)。 0 .8或 1 .6mT磁场作用 2 4h时CFIRR的Md 分别 8.2 5、6 .68% /min ,与空白对照组比较 ,差异无显著性 (H =32 .61 7,P >0 .0 5)。 0 .8或 1 .6mT磁场作用 2 3h ,再与TPA共同作用 1h时CFIRR的Md 分别为 3 .32、2 .85% /min ,与TPA组比较 ,差异无显著性 (H =2 .589,P >0 .0 5)。结论　 0～ 1 .6mT的 50Hz磁场单独作用不能抑制星形胶质细胞GJIC功能 ;协同TPA ,不能增强TPA对星形胶质细胞GJIC的抑制作用 ;但是磁场对星形胶质细胞GJIC的抑制作用随着磁场强度增强呈递增趋势     

肝细胞癌SCT表现特征与Rb,PCNA的关系

目的　探讨肝细胞癌 (HCC)SCT (spiralCT)表现特征与癌细胞中视网膜母细胞瘤基因(Rb)、增殖细胞核抗原 (PCNA)表达的关系。方法　对 39例 (41个病灶 )经手术病理证实且行SCT动、静脉双期增强扫描的肝细胞癌病例 ,观察每个病灶的SCT表现特征 :肿瘤的大小、包膜、侵袭危险性、强化类型和肝硬化情况。用免疫组化法检测癌组织中Rb ,PCNA表达 ,分析评价SCT表现特征与蛋白之间的关系。结果　HCCSCT图像中肿瘤大小、包膜形成、侵袭危险性、强化类型和周围肝组织有无硬化与Rb蛋白之间无统计学意义 (P >0 .0 5 )。肿瘤大小、侵袭危险性、强化类型与PCNA之间有统计学意义 (P <0 .0 5 )。结论　肝细胞癌的SCT表现特征与PCNA的表达相关 ,根据其表现特征 ,可在一定程度上推测肿瘤组织PCNA表达情况 ,这有助于HCC的早期诊断及治疗方案的选择     

小儿胸壁巨细胞纤维母细胞瘤一例报告

巨细胞纤维母细胞瘤(giant cell fibroblastoma．GCF)是一种较罕见的软组织肿瘤。我院收治1例．报告如下。     

局灶脑缺血恢复期半影区小胶质细胞可塑性变化和bFGF表达规律探讨

目的 观察Wistar大鼠大脑中动脉永久性闭塞后不同时段，缺血半影区小胶质细胞和神经元形态学变化及bFGF在皮层和海马的表达规律。方法 将雄性Wistar大鼠48只，随机分为假手术对照组和永久性局灶性脑缺血组，后者再根据缺血时间不同分5个亚组。假手术组：仅暴露大脑中动脉，2h后断头取脑。永久性局灶性脑缺血组：建立大鼠大脑中动脉闭塞模型，分别于缺血后3d、7d、14d、28d、42d断头取脑，行HE和免疫组化染色。观察梗死灶周围半影区的小胶质细胞和神经元的形态学变化和bFGF在皮层及海马部位的表达规律。结果 HE染色可见脑缺血3d时半影区有少量小胶质细胞出现，14d小胶质细胞增多达高峰，42d趋于稳定。脑缺血3d梗死灶周围皮质神经元和胶质细胞开始表达bFGF，7d表达增强，14d达高峰，28d表达开始减弱，42d仍有一定表达，bFGF在海马的表达也有相同规律。结论 小胶质细胞的肥大和增生性变化以及bFGF的表达，不仅发生于脑缺血早期，晚期仍显示持续性变化，表明小胶质细胞活动以及bFGF的表达贯穿于脑缺血的整个病理过程。