NMDA受体NR1、NR2A/B在丘脑前核-海马CA1、CA3脑区和齿状回的分布与表达

目的 探讨NMDA受体NR1、NR2A/B在丘脑前核-海马CA1、CA3脑区和齿状回的分布与表达,以及丘脑前核-海马神经元的学习记忆功能及作用机制.方法 运用原位杂交检测技术观测丘脑前核及海马CA1、CA3和齿状回内NMDA受体NR1、NR2A 及NR2B mRNA的分布特点.结果 ①原位杂交阳性产物呈棕黄色,主要分布在神经元的胞浆中,胞核基本不着色.②在丘脑前核,阳性神经元分布较密集,细胞形态较一致.③在海马锥体层阳性神经元分布较多,呈带状.在分子层、多形层分布少.④NR1、NR2A/B在丘脑前核和海马CA1、CA3脑区及齿状回均有表达,其中NR1在齿状回表达水平最强,NR2B在丘脑前核、海马CA1、CA3和齿状回表达水平基本相同.结论 在丘脑前核-海马的局部神经元环路中NMDA受体NR1、NR2A及NR2B mRNA分布广泛.其中NR2B mRNA在丘脑前核和海马CA1、CA3脑区及齿状回表达水平基本相同,可能与此环路学习记忆有关.     

大鼠学习记忆时CA3区突触素免疫阳性产物的变化及突触出芽表达

目的探讨学习记忆的形成、遗忘与突触可塑性的关系。方法用水迷宫训练大鼠21d建立空间辨别性学习记忆模型，随即停止训练，应用免疫组化方法和图像分析技术，检测3、7、14d突触素在大鼠海马CA3区表达的变化。结果对照组大鼠海马CA3区突触素的表达弱，免疫反应产物呈点状颗粒，沿辐射层长轴分布，多形层也有散在分布。模型组大鼠突触素染色明显比对照组深，密集的小颗粒呈带状沿辐射层排列，底部可见一些大的阳性颗粒。随着停止训练的时间延长，突触素的表达逐渐减弱。结论空间学习记忆导致海马CA3区辐射层新突触的形成，而随着空间学习记忆的遗忘，又致新形成突触的消退或突起的出芽又逐渐消失。     

早期恐惧声音应激对大鼠远期学习记忆能力及海马CA1区5-HT1AR-CREB-BDNF信号通路的影响

目的观察早期恐惧声音应激对大鼠远期学习记忆功能及海马CA1区5-羟色胺1A受体(5-HT1AR)、环磷腺苷效应元件结合蛋白(CREB)、脑源性神经营养因子(BDNF)表达的影响。方法 40只出生后1 d的健康新生SD雄性大鼠随机分为对照组和应激组各20只。应激组以恐惧的声音为应激源,于每日上、下午各播放2 h,持续21 d,建立早期恐惧声音应激模型;对照组于正常环境下饲养。应激结束后5 w行Morris水迷宫实验检测学习记忆能力;水迷宫实验结束后断头取脑,苏木精-伊红(HE)染色观察海马区的病理情况,免疫荧光组织化学法和蛋白免疫印迹法检测大鼠海马CA1区5-HT1AR、CREB和BDNF蛋白表达。结果与对照组相比,应激组学习记忆能力明显下降(P<0.01);对照组海马CA1区的神经元结构整齐、排列紧密,而应激组海马CA1区的神经元排列疏松并且出现了神经元的丢失;与对照组相比,应激组海马CA1区的5-HT1AR、CREB和BDNF蛋白表达均明显降低(P<0.01)。结论早期恐惧声音应激可导致大鼠成年后学习记忆功能障碍,其机制可能与早期恐惧声音应激抑制5-HT1AR-CREB-BDNF信号通路有关。     

丁苯酞对慢性酒精中毒大鼠海马硫化氢及CA1、CA3区五羟色胺的影响

目的探讨丁苯酞(NBP)对慢性酒精中毒大鼠学习记忆能力、海马硫化氢及CA1、CA3区五羟色胺(5-HT)含量的影响。方法将90只SD雄性大鼠随机平均分为五组,除对照组外,各组饮含6%(V/V)酒精水溶液42 d,酒精溶液每日9∶00配制,置换。42 d后,NBP低、中、高剂量组灌胃不同剂量NBP(大约14 d),于饮酒结束后采用Y型电迷宫测试酒精中毒大鼠的学习记忆能力,随后检测海马组织H_2S的含量及CA1、CA3区5-HT的表达情况。结果与空白对照组相比,模型组学习记忆和H_2S含量均显著升高,5-HT受体阳性表达显著降低(P0.01)。与模型组相比,NBP中、高剂量组学习记忆成绩和H2S含量均显著降低,5-HT受体阳性表达显著升高(P0.01)。结论 NBP能够减轻慢性酒精中毒大鼠的症状,改善大鼠学习记忆能力,可能与NBP影响H_2S和5-HT的含量有关。     

大鼠海马CA3区谷氨酸能、γ-氨基丁酸能神经元的增龄性变化

目的 探讨大鼠海马CA3区谷氨酸能、γ-氨基丁酸(GABA)能神经元增龄性变化的规律.方法 SD大鼠分为1～2,4～5,11～12和≥24月龄4组,常规石蜡海马连续冠状切片,HE染色和谷氨酸、GABA免疫组织化学染色,图像分析仪测量谷氨酸、GABA免疫反应阳性产物的光密度及其阳性神经元的多种形态学参数.结果 大鼠海马CA3区谷氨酸、GABA免疫反应阳性产物的光密度及其阳性神经元多种形态学参数随增龄而减小.结论 海马CA3区谷氨酸、GABA能神经元随年龄增长而逐渐出现衰老性变化,为海马衰老病变的研究提供形态学依据.     

脑缺血再灌注大鼠学习记忆能力和海马组织CREB、C/EBP的DNA结合活性改变

目的观察脑缺血再灌注大鼠学习记忆能力和海马组织环磷酸腺苷反应(cAMP)元件结合蛋白(CREB)及CCAAT/增强子结合蛋白(C/EBP)的DNA结合活性改变。方法采用4血管法制备大鼠缺血再灌注损伤模型,用水迷宫检测大鼠学习记忆能力,HE染色观察海马CA1区神经元形态改变,凝胶电泳迁移率改变分析法(EMSA)测定CREB和C/EBP的DNA结合活性。结果水迷宫检测:与假手术组术比较,模型组大鼠逃逸潜伏期明显延长(P<0.05),跨越平台次数明显减少(P<0.05)。HE染色:假手术组大鼠海马CA1区神经元排列整齐、均匀,细胞结构完整;模型组大鼠海马CA1区部分神经元正常结构消失,胞核区域浓染,出现凝固性坏死及细胞脱失,海马CA1区正常神经细胞数目较假手术组明显减少(P<0.05)。EMSA检测:模型组大鼠海马组织CREB和C/EBP的DNA结合活性均较假手术组显著降低(P<0.01)。结论 CREB和C/EBP的DNA结合活性下降可能参与了脑缺血再灌注损伤引起的神经元损伤和学习记忆能力下降。     

软脉灵口服液对拟血管性痴呆大鼠学习记忆和海马CA1区神经元凋亡的影响

目的观察软脉灵口服液对实验性血管性痴呆（VaD）大鼠空间学习记忆能力和海马CA1区神经元凋亡的影响。方法选用永久性结扎双侧颈总动脉（2VO）制作VaD模型,用Morris水迷宫测定大鼠学习记忆能力,HE染色观察大鼠海马CA1区的形态学变化,TUNEI．染色观察大鼠海马CA1区的神经元凋亡情况。结果与模型组比较,软脉灵高剂量组逃避潜伏期缩短（P〈0．001）、1min穿越原平台所在位置次数增加（P〈0．001）;软脉灵高剂量组与低剂量组大鼠海马CA1区的凋亡细胞比模型组减少（P〈0．01）;与软脉灵低剂量组比较．高剂量组大鼠海马CA1区的凋亡细胞更少（P〈0．01）。结论软脉灵口服液能改善拟VaD尢鼠的空间学习记忆能力,减少拟VaD大鼠海马CA1区的凋亡细胞。这些作用呈一定的量效关系。     

钙结合蛋白在老年人海马CA1和CA3区的分布

目的　探讨老年人海马中钙结合蛋白 (CalbindinD 2 8K ,CaBP)的分布及表达 ,并分析其在人衰老过程中对神经元的生理、病理变化的影响。方法　收集 12例 6 0岁以上老年人非脑部疾病尸检左侧大脑半球的海马组织 ,经病理常规处理后 ,切片 ,用免疫组织化学ABC染色法检测海马CA1与CA3区CaBP的分布。结果　CaBP阳性产物出现在神经元的细胞质中 ,CA1区的CaBP免疫阳性细胞数多于CA3区。结论　CaBP在老年人海马CA1、CA3中均有表达 ,但有差别。提示CaBP在老年人海马的功能活动中可能起重要作用。     

β-淀粉样蛋白对大鼠海马S100β表达及学习记忆的影响

目的　探讨 β-淀粉样蛋白 (Aβ)沉积与大鼠海马 S1 0 0 β表达的相关性及其在大鼠学习记忆中的作用。方法　采用不同浓度的 Aβ2 5-35选择大鼠海马 CA1区进行定位注射 ,通过行为学测试、光镜形态学观察 ,免疫组化染色的方法 ,观测大鼠学习记忆、海马 CA1区神经元和 S1 0 0β阳性细胞形态、数目的变化。结果　术后 7d,随着 Aβ2 5- 35脑内注射浓度的增加 ,实验组较对照组大鼠的学习记忆能力明显下降 (P<0 .0 5) ,海马CA1区神经元数目明显减少 (P<0 .0 5) ,而 S1 0 0β阳性细胞数则显著增多 (P<0 .0 5)。结论　 Aβ2 5- 35可以明显上调 S1 0 0β的表达 ,两者之间存在剂量效应关系 ;Aβ2 5- 35具有神经毒性作用 ,可以引起海马神经元丢失 ,造成大鼠学习记忆下降 ;S1 0 0 β的高水平表达可能与海马 CA1区神经元丢失以及大鼠的学习记忆下降有密切关系。     

电针对拟老年性痴呆大鼠学习记忆功能和海马CA1区突触可塑性的影响

目的 探讨电针对拟老年性痴呆(AD)大鼠学习记忆功能和海马CA1区突触可塑性的影响.方法 采用腹腔注射D-半乳糖、东莨菪碱,胃饲三氯化铝(AlCl3)制备多因素损伤拟AD动物模型,在造模同时给予电针干预,应用跳台实验检测大鼠学习和记忆能力,HE染色观察海马CA1区形态学变化,免疫组化测定海马区CA1区突触素表达水平,透射电镜测定突触面数密度、面积密度和体积密度变化.结果 电针能明显改善拟AD大鼠学习记忆能力,增加海马CA1区神经元数目,上调突触素表达.结论 ①多因素损伤能成功制备拟AD大鼠动物模型.②电针促进海马CA1区重建而提高突触素表达可能是改善拟AD鼠的学习记忆功能的机制之一.     

血清CA125,CA19-9,CA50含量对消化系肿瘤的诊断价值

目的评价血清CA125,CA19-9,CA50含量对消化系肿瘤的诊断价值.方法消化系肿瘤患者158例,其中肝癌38例,食管癌21例,胃癌56例,结直肠癌36例,胰腺癌7例;消化系良性疾病患者106例,其中肝硬变57例,消化性溃疡49例;正常对照者40例.全部受测对象均空腹抽静脉血,分离血清,-20℃贮存备测.采用RIA法测定血清CA125,CA19-9,CA50含量,使用国产SN-695型γ计数仪.数据均用()±s表示,以正常()±2s作为上限计算阳性率.结果肝癌、胃癌、胰腺癌、结直肠癌和食管癌血清(CA含量均以kU/L表达)CA125(分别为222±116,79±17,135±79,69±23和72±26),CA19-9(237±108,281±132,838±224,252±136和273±146)和CA50含量(25±9,20±7,18±9,18±8和17±7)显著高于正常对照组及消化道良性病变组(P＜0.01).消化道肿瘤有腹腔及远处转移者,其血清CA125,CA19-9,CA50含量升高更为明显.结论血清CA125,CA19-9,CA50均为较好的肿瘤标记物,有助于诊断消化系统肿瘤.     

Diagnostic value of serum CA242, CA 19-9, CA 15-3 and CA 125 in patients with carcinoma of the gallbladder.

BACKGROUND: Tumor markers have an increasing significance in the diagnosis and evaluation of tumor, but their role in gallbladder cancer has not been established. The present study was undertaken to determine the utility of serological markers in carcinoma of the gallbladder (CaGB). METHODS: This study was carried out in 55 cases and 8 healthy controls presenting to a single surgical unit of the University Hospital, Varanasi, India. CA242, CA19-9, CA15-3 and CA125 were assayed preoperatively in serum of patients with carcinoma of the gallbladder (39), cholelithiasis (16) and healthy controls (8) using ELISA technique. RESULTS: Mean concentration of all tumor markers was significantly raised in carcinoma of the gallbladder when compared with cholelithiasis. CA 242 was 12.10 vs 42.19 u/ ml, CA19-9 was 211.27 vs 86.06 uml, CA 15-3 was 71.42 vs 1.93u/ml and CA125 was 253.61 vs 65.5 u/ml <0.05). Sensitivity and specificity were calculated at various cut off points. Significant changes in CAl9-9 and CA242 occurred with advanced stage (p <0.05) and grade of tumor (p<0.00 1). When two tumor markers were combined, like CA242 and CA125, sensitivity and specificity improved to 87.5% and 85.7% respectively. Diagnostic accuracy is highest with a combination of CA 19-9 and CA 125 (80.65%). However, combination of tumor markers did not improve any further sensitivity or specificity of markers. CONCLUSION: Assay of CA242, CA15-3, CA19-9 and CA 125 are fairly good markers for discriminating patients of carcinoma of the gallbladder from cholelithiasis. CA242 and CA125 when used together achieved best sensitivity and specificity. Serum markers seem to be less sensitive when used individually in carcinoma of the gallbladder but may prove useful in combination.     

Topographic specificity of functional connections from hippocampal CA3 to CA1

The hippocampus is a cortical region thought to play an important role in learning and memory. Most of our knowledge about the detailed organization of hippocampal circuitry responsible for these functions is derived from anatomical studies. These studies present an incomplete picture, however, because the functional character and importance of connections are often not revealed by anatomy. Here, we used a physiological method (photostimulation with caged glutamate) to probe the fine pattern of functional connectivity between the CA3 and CA1 subfields in the mouse hippocampal slice preparation. We recorded intracellularly from CA1 and CA3 pyramidal neurons while scanning with photostimulation across the entire CA3 subfield with high spatial resolution. Our results show that, at a given septotemporal level, nearby CA1 neurons receive synaptic inputs from neighboring CA3 neurons. Thus, the CA3 to CA1 mapping preserves neighbor relations.     

胃癌患者血清CA199、CA724、CA242联合检测及其临床意义

目的 探讨血清肿瘤相关抗原CA199、CA724和CA242水平与胃癌的关系.方法 采用放射免疫法分别对63例胃癌患者血清CA199、CA724和CA242水平进行检测,并与30例慢性萎缩性胃炎伴重度不典型增生(CAGD)、30例正常对照组比较,分析其与胃癌恶性程度、转移和临床分期的关系.结果 胃癌患者血清CA199、CA724和CA242水平均明显高于CAGD与正常对照组(P均<0.01),血清CA199、CA724和CA242的阳性率与胃癌恶性程度、转移和临床分期有关(P<0.05),三项指标联合检测可明显提高胃癌诊断的敏感度及准确性.结论 胃癌患者血清CA199、CA724和CA242水平是胃癌发生、发展的重要因素,三者联合检测对胃癌患者诊断、治疗和预后判断等具有重要意义.     

RNAi knockdown of PIK3CA preferentially inhibits invasion of mutant PIK3CA cells

AIM: To explore the effects of siRNA silencing of PIK3CA on proliferation, migration and invasion of gastric cancer cells and to investigate the underlying mechanisms. METHODS: The mutation of PIK3CA in exons 9 and 20 of gastric cancer cell lines HGC-27, SGC-7901, BGC-823, MGC-803 and MKN-45 was screened by polymerase chain reaction (PCR) followed by sequencing. BGC-823 cells harboring no mutations in either of the exons, and HGC-27 cells containing PIK3CA mutations were employed in the current study. siRNA...     

Intralobar pulmonary sequestration presenting increased serum CA19-9 and CA125

A 39-year-old man was admitted to our hospital for further evaluation of a consolidated shadow and clarification of the cause of serum tumor marker elevation (CA19-9 496.2 U/ml, CA125 160.6 U/ml). Chest computed tomography revealed a well-defined homogeneous nodule in the left S(10). Angiography showed one aberrant artery, branching from the ascending aorta. Intralobar pulmonary sequestration was diagnosed and the sequestrated lung was resected. Microscopic findings of the sequestrated lung showed a mucus-containing cystically dilated bronchus, which was covered with ciliated cylindrical epithelium. Immunohistochemical staining showed positive staining for CA19-9 and CA125 in both the ciliated cylindrical epithelium and mucus. Serum values of tumor markers returned to their normal range after surgery.     

Serum level of TSGF, CA242 and CA19-9 in pancreatic cancer

AIM: To establish a method to detect the expression of the tumor specific growth factor TSGF, CA242 and CA19-9 in serum and evaluate their value in diagnosis of pancreatic cancer. METHODS: ELISA and Biochemical colorimetric assay were used to detect the serum content of TSGF, CA242 and CA19-9 in 200 normal cases, 52 pancreatitis patients and 96 pancreatic cancer patients. RESULTS: The positive likelihood ratios of TSGF, CA242 and CA19-9 were 5.4, 12.6 and 6.3, respectively, and their negative likelihood ratios were 0.10, 0.19 and 0.17, respectively. With single tumor marker diagnosed pancreatic cancer, the highest sensitivity and specificity of TSGF were 91.6% and 93.5%. In combined test with 3 markers, when all of them were positive, the sensitivity changed to 77.0% and the specificity and the positive predictive value were 100%. The levels of TSGF and CA242 were significantly higher in the patients with pancreatic cancer of head than those in the patients with pancreatic cancer of body, tail and whole pancreas, but the expression of CA19-9 had no correlation with the positions of the pancreatic cancer. The sensitivity of TSGF, CA242 and CA19-9 was increased with the progress in stages of pancreatic cancer. In stage I, the sensitivity of TSGF was markedly higher than CA242 and CA19-9. CONCLUSION: The combined use of TSGF, CA242 and CA19-9 expressions can elevate the specificity for pancreatic cancer diagnosis. And it shows that it plays an important role to differentiate positions and tissue typing. It is a forepart diagnosis for the pancreatic cancer by combination checking. There is very important correlation between the three markers and the pancreatic cancer.     

Thapsigargin shifts the CA set point of parathyroid cells to lower extracellular [CA]

The hypothesis that cytosolic calcium concentration ([Ca²⁺ _cyt]) is the primary regulator of parathyroid hormone (PTH) secretion is supported by a number of studies that show an inverse relationship between them. One agent shown to inhibit PTH secretion is thapsigargin, a sesquiterpene lactone that raises [Ca²⁺ _cyt] by inhibiting the Ca-ATPase that pumps Ca²⁺ from the cytosol into the lumen of the endoplasmic reticulum. Thapsigargin may act on the parathyroid cell other than to inhibit the Ca-ATPase, however, in ways that might also affect PTH secretion. We have tested its effects on functional parameters, such as protein synthesis, the exocytic machinery, and the ability of parathyroid cells to respond to different concentrations of extracellular Ca²⁺ ([Ca²⁺ _ex]). In particular, we have determined whether the inhibition of PTH secretion by thapsigargin is independent of or is modulated by changes in [Ca²⁺ _ex]. The results revealed no effects of thapsigargin on protein synthesis or the exocytic mechanisms within 2 h of treatment, and showed that [Ca²⁺ _ex] can modulate PTH secretion in the presence of thapsigargin. Its inhibition of PTH secretion, therefore, appears to rest on its ability to shift [Ca²⁺ _cyt] to higher levels, but the possibility that it interacts with the Ca receptor has not been eliminated. The results support the hypothesis that the primary regulator of steady-state PTH secretion is [Ca²⁺ _cyt].