冠状动脉球囊损伤后管壁原癌基因c-myc表达的变化

目的：探讨原癌基因c-myc的表达与冠状动脉球囊损伤后内膜增殖的关系。方法：建立猪的冠状动脉球囊损伤模型，观察形态学变化，并用RT-PCR的方法检测损伤冠状动脉壁内c-myc mRNA的表达。结果：冠状动脉球囊损伤后6周管壁内膜明显增生，管腔狭窄，c-myc mRNA的相对表达强度明显高于正常冠状动脉壁。结 论：c-myc基因与冠状动脉球囊损伤后内膜增殖密切相关。     

病毒性心肌炎原癌基因c-fos的表达

原癌基因c-fos参与了细胞的生长、分化和信息传递,它在某些疾病和病理生理过程中表达增加,可能参与其发生与发展.有关病毒性心肌炎（viral myocarditis,VMC）中c-fosmRNA的表达目前罕见报道.本研究就是利用免疫组化方法和原位杂交方法探讨原癌基因c-fos的mRNA及蛋白质在小鼠VMC心肌细胞中的表达.     

流动力对细胞原癌基因c-fos和c-myc表达的影响

目的研究流体力对脑微血管内皮细胞原癌基因c-fos和c-nyc表达的影响,为探索微血管疾病机理提供一定实验依据.方法获取Wistar大鼠脑微血管进行细胞培养,在平行板流动小室中对所培养的细胞施加力学作用,并应用免役组织化学技术观察微血管内皮细胞原癌基因c-fos和c-myc的表达.结果不同的流动力对体外培养的大鼠脑微血管内皮细胞c-fos和c-myc蛋白表达产生了不同的影响.c-fos蛋白表达在静态时非常低,但在4dynes/cm2和10dynes/cm2的流体力的作用下可诱导c-fos蛋白水平迅速增加,尤其是10dynes/cm2的流体力,并随着时间的延长而增加,到1h时达到高峰,随后c-fos蛋白表达量出现下降,2.5h时接近基础水平.c-myc蛋白在静态时表达也非常低,经流体力作用后缓慢增多.结论流体力的大小会影响c-fos和c-myc的表达,血液的力学信号传入细胞内并引起细胞的一些应答,也印证了c-fos和c-myc是被血液流体力作用短暂上调的基因,流体力与内皮细胞生长、增殖、损伤也有直接关系.     

c-fos基因及其蛋白表达与神经精神疾病的研究进展

c-fos基因及其蛋白表达在神经精神病学科日益受到重视,表文对c-fos基因进行了总体概述,并对c-fos基因及其所表达的蛋白结构、功能和作用进行了介绍,总结概括了c-fos基因及其蛋白表达与神经内分泌系统的关系;c-fos基因及其蛋白表达与中枢神经系统神经元细胞的关系;及其与精神科疾病的联系.     

微囊化异体坐骨神经组织细胞移植对大鼠脊髓损伤后c-fos表达的影响

目的探讨微囊化异体坐骨神经组织细胞移植对大鼠脊髓损伤后c-fos表达的影响。方法95只SD大鼠随机分为4组,A组为微囊化坐骨神经细胞移植组（30只）;B组为坐骨神经细胞移植组（30只）;C组为单纯损伤对照组（30只）,仅用明胶海绵填塞SCI腔隙;D组为正常对照组（5只）,仅打开椎管,暴露脊髓不作移植。用免疫组织化学的方法观察移植术后6h-14d脊髓中c-fos基因的表达情况。结果脊髓半横断损伤后对照组脊髓中6h、12h内表达c-fos阳性的神经元数增多,平均光密度值升高,至24h又明显增强。而A组脊髓后角内的c-fos表达明显低于同时间点的B组和C组（P〈0．05）。结论微囊化坐骨细胞移植可能降低c-fos的表达,并在一定程度上减轻脊髓的继发性损伤。     

银杏叶制剂对脑缺血再灌注后热休克蛋白、c-fos表达的影响

目的： 研究银杏叶制剂对大鼠脑缺血再灌注后热休克蛋白（HSP）、c-fos表达的影响，探讨其神经保护机制。 方法： 采用改良Longa法复制大鼠局灶脑缺血再灌注模型。56只实验大鼠随机分为正常对照组、假手术组、缺血再灌注组及银杏叶制剂预处理组。银杏组大鼠在实验前灌服银杏制剂2 mL，1日3次，连用5 d。应用HSP70及c-fos免疫组化染色、c-fos mRNA原位杂交、原位细胞凋亡及HE染色等方法观察缺血再灌注不同时点（1 h、6 h、12 h、24 h、3 d、7 d）两者的变化，并对其阳性结果进行半定量分析。 结果： 银杏制剂预处理组各时段神经细胞缺血程度明显轻于未处理组、TUNEL阳性细胞数明显少于未处理组，HSP70及c-fos表达的阳性细胞数则明显多于未处理组（P<0.01）。脑缺血再灌注组1 h 时c-fos即有表达，6 h达高峰，后逐渐下降。再灌注6 h组HSP70在缺血侧皮质及基底节开始表达，24 h达高峰。再灌注6 h细胞凋亡最显著。 结论： 银杏制剂可能通过诱导HSP70及c-fos的表达，发挥其神经保护作用。     

碱性成纤维细胞生长因子对成骨细胞生长与c-fos表达的影响

以重组牛碱性成纤维细胞生长因子 (rb- b FGF)刺激体外培养的大鼠成骨细胞 ,发现 :经过 1～ 2 d的刺激 ,成骨细胞产生很长的突起 ,细胞数量和活力较对照均有显著升高 ;经 rb- b FGF 1h的刺激后 ,c- fos基因的表达即明显高于对照 ,刺激 1～ 2 d后 c- fos基因的表达也明显高于对照。这表明 b FGF可促进大鼠成骨细胞增殖 ,提高c- fos基因的表达量。 c- fos表达量的提高 ,可能是各种刺激在促进细胞增殖的信号转化过程中的重要一步     

大鼠黑质损毁后多巴胺能神经元形态及纹状体c-fos表达的变化

目的:观察毁损黑质后,多巴胺(DA)能神经元形态学变化和纹状体内相关神经元c-fos表达情况,探讨c-fos表达与毁损程度的关系。方法:利用6羟多巴胺(6OHDA)特异毁损大鼠黑质DA能神经元,采用阿朴吗啡(APO)诱导旋转实验观察术后1、7、14和21d行为学变化;利用HE染色、Nissl染色、免疫组织化学方法和电镜,观察各时间点黑质DA能神经元形态学变化和纹状体c-fos表达。结果:毁损侧DA能神经元逐渐减少,超微结构损伤逐渐加重;DA神经元丢失比例≥80%时,纹状体毁损侧c-fos表达上调,APO诱导的旋转实验>7r/min。结论:黑质DA能神经元丢失是毁损大鼠行为改变的病理学基础;cfos的表达与DA能神经元的毁损程度、行为改变有一定的关系。     

猪冠状动脉球囊损伤后管壁cyclin D1和Rb蛋白表达的变化

目的：探讨原癌基因cyclin D₁和抑癌基因Rb的表达与猪冠状动脉球囊损伤后内膜增殖的关系。方法：应用免疫组化法检测猪冠状动脉球囊损伤后壁内cyclin D₁和Rb蛋白的表达。结果：增生的内膜和中膜内cyclin D₁和Rb蛋白表达阳性,阳性细胞呈点片状分布,阳性强度与内膜增生程度有关,两个基因的表达具有相关性。结论：cyclin D₁和Rb基因与猪冠状动脉球囊损伤后内膜增殖密切相关。     

高血压冠状动脉平滑肌细胞的形态学变化

既往研究表明,高血压伴随有血管壁中层血管平滑肌细胞（ＶＳＭＣ）的肥大〔１,２〕。但是高血压未形成时冠状动脉中层ＶＳＭＣ是否已存在肥大及抗高血压药物对ＶＳＭＣ肥大的影响尚不清楚。本研究以自发性高血压大鼠（ＳＨＲ）和同种系正常血压的京都种大鼠（ＷＫＹ）为动物模型,通过观察ＳＨＲ高血压形成前后及抗高血压药物罗沙坦治疗后,左冠状动脉前降支中层ＶＳＭＣ的形态变化,了解高血压冠状动脉ＶＳＭＣ的形态学变化及抗高血压药物治疗对其的影响。１　材料和方法１１　实验动物及分组　雄性ＳＨＲ和ＷＫＹ由上海市高血压研究所…     

Anti-inflammatory effect of abciximab-coated stent in a porcine coronary restenosis model

The aim of this study was to examine the anti-inflammatory effect of abciximab-coated stent in a porcine coronary overstretch restenosis model. Ten abciximab-coated stents, ten sirolimus-eluting stents (SES), and ten paclitaxel-eluting stents (PES) were deployed with oversizing (stent/artery ratio 1.3:1) in porcine coronary arteries, and histopathologic analysis was done at 28 days after stenting. There were no significant differences in the neointima area normalized to injury score and inflammation score among the three stent groups (1.58 +/- 0.43 mm(2), 1.57 +/-0.39 mm(2) in abciximab-coated stent group vs. 1.69 +/- 0.57 mm(2), 1.72 +/- 0.49 mm(2) in the SES group vs. 1.92 +/- 0.86 mm(2), 1.79 +/- 0.87 mm(2) in the PES group, respectively). In the neointima, most inflammatory cells were lymphohistiocytes. Significant positive correlations were found between the extent of inflammatory reaction and the neointima area (r=0.567, p<0.001) and percent area stenosis (r=0.587, p<0.001). Significant correlations were found between the injury score and neointimal area (r=0.645, p<0.001), between the injury score and the inflammation score (r=0.837, p<0.001), and between the inflammation score and neointimal area (r=0.536, p=0.001). There was no significant difference in the inflammatory cell counts normalized to injury score among the three stent groups (75.5 +/- 23.1/microL in abciximabcoated stent group vs. 78.8 +/- 33.2/microL in the SES group vs. 130.3 +/- 46.9/microL in the PES group). Abciximab-coated stent showed comparable inhibition of inflammatory cell infiltration and neointimal hyperplasia with other drug-eluting stents in a porcine coronary restenosis model.     

Single-cell imaging of c-fos expression in rat primary hippocampal cells using a luminescence microscope

Methods to study gene expression in live cells over time have been limited. One known method is the luciferase assay, which measures the luminescence of luciferase by coupling its expression to the promoter of a gene under study. This luminescence in cells can be measured over time by a luminometer. One major drawback of the luminometer, however, is that it can only measure the luminescence of a group of cells, and cannot follow the differences that may exist among individual cells. A novel luminescence microscope allows the visualization of individual luminescent cells over time through CCD photography. In this study, live single cells of the rat hippocampus were observed under the microscope for luciferase expression driven by the c-fos promoter. We showed that the cell body and neurite areas within a single neuron exhibited differences in luminescence. Because this microscope could detect differences among subcellular regions of single-cell, it may be a promising novel tool to study polarized cells like neurons, and to elucidate proteins involved in neuronal processes such as dendritic/axonal targeting and synaptogenesis.     

SNCA和PARK16多态性与中国辽宁地区汉族帕金森病人的关联分析

目的: 探究SNCA基因rs3857059和PARK16基因rs16856139单核苷酸多态性(SNPs)的频率分布及与帕金森病的关联性。方法: 本研究以214名中国辽宁地区汉族健康个体和213名帕金森病患者为研究对象,借助多重PCR及单一的限制性内切酶消化后的限制性片段长度多态性(RFLP)分析技术,对上述2种帕金森病易感基因中的2个SNPs位点进行等位基因多态性调查,并将所得的对照及病例组数据进行相关统计分析。结果: 多重PCR-RFLP法成功地检测出2个SNPs位点的所有基因型。基因频率数据显示rs3857059位点的G等位基因频率在帕金森病患者组高于对照组,差异有统计学意义(χ²=7.592,P<0.01,OR= 0.677,95% CI=0.517~0.888);rs16856139位点的T等位基因频率在帕金森病患者组低于对照组,差异有统计学意义(χ²=11.511,P< 0.01,OR= 0.390, 95% CI=0.227~0.669),这些结果提示本研究调查的2个SNPs构成了帕金森病患病的危险因素。结论: 帕金森病易感基因SNCA的rs3857059和PARK16的rs16856139位点基因频率分布在中国辽宁地区汉族群体中与帕金森病相关。     

Shrimp Pm-fortilin inhibits the expression of early and late genes of white spot syndrome virus (WSSV) in an insect cell model

Fortilin plays an important role in anti-apoptotic mechanisms and cell proliferation in many eukaryotic organisms. This work confirmed previous reports that Sf9 can support the replication of white spot syndrome virus (WSSV) genomic material by using immunohistochemistry with a specific antibody to detect the immediate early gene 1 (ie1) and by amplification of WSSV DNA and mRNA products. Using this insect-cell model system, we show that overexpression of Pm-fortilin in Sf9 cells inhibited the expression of WSSV early genes and late genes (WSSV-DNA polymerase, VP15 and VP28) but not an immediate early gene ie1. This is the first time that an insect cell line has been used to demonstrate interaction between a shrimp gene and genes of a shrimp virus.     

Fos expression following regimens of predator stress versus footshock that differentially affect prepulse inhibition in rats

Stress is suggested to exacerbate symptoms and contribute to relapse in patients with schizophrenia and several other psychiatric disorders. A prominent feature of many of these illnesses is an impaired ability to filter information through sensorimotor gating processes. Prepulse inhibition (PPI) is a functional measure of sensorimotor gating, and known to be deficient in schizophrenia and sometimes in post-traumatic stress disorder (PTSD), both of which are also sensitive to stress-induced symptom deterioration. We previously found that a psychological stressor (exposure to a ferret without physical contact), but not footshock, disrupted PPI in rats, suggesting that intense psychological stress/trauma may uniquely model stress-induced sensorimotor gating abnormalities. In the present experiment, we sought to recreate the conditions where we found this behavioral difference, and to explore possible underlying neural substrates. Rats were exposed acutely to ferret stress, footshock, or no stress (control). 90 min later, tissue was obtained for Fos immunohistochemistry to assess neuronal activation. Several brain regions (prelimbic, infralimbic, and cingulate cortices, the paraventricular hypothalamic nucleus, the paraventricular thalamic nucleus, and the lateral periaqueductal gray) were equally activated following exposure to either stressor. Interestingly, the medial amygdala and dorsomedial periaqueductal gray had nearly twice as much Fos activation in the ferret-exposed rats as in the footshock-exposed rats, suggesting that higher activation within these structures may contribute to the unique behavioral effects induced by predator stress. These results may have implications for understanding the neural substrates that could participate in sensorimotor gating abnormalities seen in several psychiatric disorders after psychogenic stress.     

Compartmentalized expression of light-induced clock genes in the suprachiasmatic nucleus of the diurnal grass rat (Arvicanthis niloticus)

Photic responses of the circadian system are mediated through light-induced clock gene expression in the suprachiasmatic nucleus (SCN). In nocturnal rodents, depending on the timing of light exposure, Per1 and Per2 gene expression shows distinct compartmentalized patterns that correspond to the behavioral responses. Whether the gene- and region-specific induction patterns are unique to nocturnal animals, or are also present in diurnal species is unknown. We explored this question by examining the light-induced Per1 and Per2 gene expression in functionally distinct SCN subregions, using diurnal grass rats Arvicanthis niloticus. Light exposure during nighttime induced Per1 and Per2 expression in the SCN, showing unique spatiotemporal profiles depending on the phase of the light exposure. After a phase delaying light pulse (LP) in the early night, strong Per1 induction was observed in the retinorecipient core region of the SCN, while strong Per2 induction was observed throughout the entire SCN. After a phase advancing LP in the late night, Per1 was first induced in the core and then extended into the whole SCN, accompanied by a weak Per2 induction. This compartmentalized expression pattern is very similar to that observed in nocturnal rodents, suggesting that the same molecular and intercellular pathways underlying acute photic responses are present in both diurnal and nocturnal species. However, after an LP in early subjective day, which induces phase advances in diurnal grass rats, but not in nocturnal rodents, we did not observe any Per1 or Per2 induction in the SCN. This result suggests that in spite of remarkable similarities in the SCN of diurnal and nocturnal rodents, unique mechanisms are involved in mediating the phase shifts of diurnal animals during the subjective day.     

Investigating the role of BDNF and CCK system genes in suicidality in a familial bipolar cohort

Background

Suicidal behaviour is a phenotype widely associated with psychiatric disorders such as major depressive disorder and bipolar disorder. However, recent evidence indicates that part of the heritability of suicidal behaviour is independent of the heritability of individual psychiatric disorders. This allows investigation into genetic risk factors for suicidal behaviour within a disorder using a candidate gene association approach.

Methods

We used family-based association testing in a cohort of 130 multiplex bipolar pedigrees, comprising 795 individuals, to look for associations between suicidal behaviour and 32 single nucleotide polymorphisms (SNPs) from across the genes brain-derived neurotrophic factor (BDNF), cholecystokinin (CCK) and the cholecystokinin beta-receptor (CCKBR).

Results

We found associations (p≤0.05) between suicide attempt and 12 SNPs of CCKBR and five SNPs of BDNF. After correction for multiple testing, seven SNPs of CCKBR remained significantly associated. No association was found between CCK and suicidal behaviour.

Limitations

The study relied on retrospective self-reporting by individuals to determine phenotype, and the sample size was relatively small.

Conclusions

The results of the study support the hypothesis that some CCKBR polymorphisms may contribute to an underlying predisposition towards suicidal behaviour in bipolar disorder.     

Maternal prenatal stress in rats influences c-fos expression in the spinal cord of the offspring

Previous studies in humans have reported a link between maternal stress and disturbed infant physiological behavior. The objective of our study was to examine in experimental rats how maternal prenatal stress induced by a forced swim test affects offspring afferent spinal responses mediated by stimulation of vaginocervical receptors. The activation of spinal cord neurons showing c-fos expression was examined following vaginocervical mechanical stimulation in adult rats, which were the offspring of dams exposed to gestational stress from E10 until delivery. Vaginocervical stimulation of both prenatal-stressed and non-prenatal-stressed rats induced an increase in immunoreactive protein in the spinal cord ranging from T12 to S1 segmental levels. However, a significantly higher (40%) increase in the expression of Fos-immunoreactive neurons was observed in vaginocervical stimulated prenatally stressed rats than in non-stimulated prenatally stressed ones. This increase was higher in L5-S1 levels than in T12-L4. When the regional distribution was examined, results showed that up to 80% of activated neurons were located in the dorsal horn in both non-stimulated prenatally stressed and stimulated prenatally stressed groups, with a significantly higher density in the latter. Our results demonstrate that maternal prenatal stress can have consequences on vaginocervical responses conveyed to the spinal cord. The increase in Fos labeled neurons in T12-S1 in prenatally stressed rats induced by vaginocervical stimulation suggests the hypersensitivity of the genital tract associated with activation of spinal circuits spanning multiple segments.