Specific pattern of ionic channel gene expression associated with pacemaker activity in the mouse heart

Even though sequencing of the mammalian genome has led to the discovery of a large number of ionic channel genes, identification of the molecular determinants of cellular electrical properties in different regions of the heart has been rarely obtained. We developed a high-throughput approach capable of simultaneously assessing the expression pattern of ionic channel repertoires from different regions of the mouse heart. By using large-scale real-time RT-PCR, we have profiled 71 channels and related genes in the sinoatrial node (SAN), atrioventricular node (AVN), the atria (A) and ventricles (V). Hearts from 30 adult male C57BL/6 mice were microdissected and RNA was isolated from six pools of five mice each. TaqMan data were analysed using the threshold cycle ( C _t) relative quantification method. Cross-contamination of each region was checked with expression of the atrial and ventricular myosin light chains. Two-way hierarchical clustering analysis of the 71 genes successfully classified the six pools from the four distinct regions. In comparison with the A, the SAN and AVN were characterized by higher expression of Navβ1, Navβ3, Cav1.3, Cav3.1 and Cavα2δ2, and lower expression of Kv4.2, Cx40, Cx43 and Kir3.1. In addition, the SAN was characterized by higher expression of HCN1 and HCN4, and lower expression of RYR2, Kir6.2, Cavβ2 and Cavγ4. The AVN was characterized by higher expression of Nav1.1, Nav1.7, Kv1.6, Kvβ1, MinK and Cavγ7. Other gene expression profiles discriminate between the ventricular and the atrial myocardium. The present study provides the first genome-scale regional ionic channel expression profile in the mouse heart.     

钛颗粒负荷对成骨细胞白细胞介素6生成的影响

磨损碎屑颗粒所诱发的无菌性松动是人工关节置换术后最常见的并发症.研究表明,假体-骨界面的骨组织细胞吞噬磨屑颗粒后,以自分泌或旁分泌的方式释放细胞间介质因子,而引起假体旁骨改建紊乱,导致假体松动.为了探明不同直径的磨屑颗粒对细胞释放细胞间介质因子的影响,本研究采用3种不同直径(mean sizeφ0.9 μm、φ2.7μm、φ6.9 μm)的钛颗粒,在浓度分别为0.25wt%,0.1wt%,0.05wt%下与兔成骨细胞共孵育4、8、12、24、36、48 h后,检测各组细胞白介素6(IL-6)分泌的变化情况.结果表明,3种钛颗粒均能刺激成骨细胞分泌IL-6因子,但其上调作用因不同直径,不同负荷浓度,不同负荷时间而有所不同.随着浓度增加和时间的推移,φ2.7μm和φ6.9 μm钛颗粒对IL-6生成的上调作用持续升高,而φ 0.9 μm钛颗粒的上调作用却呈先升高后快速下降的双相变化过程.结果提示磨屑颗粒能明显刺激细胞释放细胞间介质因子IL-6,而颗粒直径大小不同,上调IL-6的程度有所不同,使得细胞间介质因子影响假体旁骨改建紊乱的机制有所不同,这种由细胞因子介导的信号传递机制若进一步深入研究必将有助于人工关节材质的优化选择及临床预防用药指导.     

肝纤维化门静脉压力改变与血清ET-1/NO关系的实验研究

目的制作兔肝纤维化模型，观察血管活性物质与门静脉压力变化的关系。方法40只家兔采用口服硫代乙酰胺方法造模，分别于造模第8、12、16、20周时检测内皮素（ET-1）及NO浓度，超声观察胆囊壁及肝脏血流动力学指标，直接穿刺测量不同时期门静脉压力。分析血管活性物质与肝脏血流动力学指标及门静脉压力变化间的关系。结果胆囊壁增厚是肝纤维化阶段的二维超声表现；随着纤维化程度的加重，血清ET-1、NO浓度逐渐增加，且以ET-1／N0比值增加更为明显；门静脉内压力、肠系膜上动脉、脾动脉搏动指数（PI）随纤维化程度逐渐增加，实验组与对照组间差异有统计学意义（P〈0．05），且与ET-1／NO值呈正相关（P〈0．01）。结论通过超声可无创检测肝脏血流动力学变化，对肝纤维化临床诊断及治疗效果的观察，具有积极的作用。     

Association of the CTLA-4 gene with rheumatoid arthritis in Chinese Han population

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is important for downregulation of T-cell activation, and CTLA-4 gene polymorphisms have been implicated as risk factors for rheumatoid arthritis (RA). Previous studies of the association between the +49 polymorphism of the CTLA-4 gene in RA have provided conflicting results. In order to determine association of the CTLA-4 gene with RA in Chinese Han population, we used denaturing gradient gel electrophoresis (DGGE) to genotype polymorphisms of four SNPs (MH30, +49, CT60 and JO31) of the CTLA-4 gene in 326 RA patients and 250 healthy controls. Furthermore, meta-analysis of all available studies relating +49 polymorphism to the risk of RA was performed to confirm the disease association. Among the SNPs examined, the genotype frequencies of CTLA-4 +49 and CT60 in RA patients differed significantly from controls (P=0.028 and 0.007). In addition, the distribution of four haplotypes constructed by these two SNPs was significantly different between patients and controls (chi(2)=10.58, d.f. =3, P=0.014). The meta-analysis also revealed that in both European and Asian populations, the CLTA-4 +49 G allele was associated with the risk of RA. These results suggested that the CTLA-4 gene might be involved in the susceptibility to RA in the Chinese Han population and both +49 and CT60 of CTLA-4 gene might be the causal variants in RA disease.     

青春期糖尿病雄鼠血清和性腺血管紧张素转换酶活性变化

４０日龄雄性Ｗｉｓｔａｒ大鼠２１只，分为对照（Ｃ）组，腹腔内注射赋形剂和糖尿病（Ｄ）组，腹腔内注射链脲菌素（ｓｔｒｅｐｔｏｚｏｔｏｃｉｎ，ＳＴＺ），５５ｍｇ／ｋｇ体重，观察６０天。结果表明，Ｄ组大鼠的睾丸、附睾、附睾尾重量显著低于Ｃ组（Ｐ＜０．０１）；Ｄ组附睾尾精子计数显著少于Ｃ组（Ｐ＜０．００１）。ＡＣＥ活性测定结果表明，Ｄ组睾丸和附睾尾组织ＡＣＥ活性显著低于Ｃ组（Ｐ＜０．０５），而血清ＡＣＥ显著高于Ｃ组（Ｐ＜０．０１），相关检验显示，附睾重量，附睾尾精子计数与附睾尾ＡＣＥ水平呈显著正相关（Ｐ＜０．０１），与血清ＡＣＥ呈显著负相关（Ｐ＜０．０５，Ｐ＜０．０１）。     

Rice as a model for centromere and heterochromatin research

Rice (Oryza sativa) has become an important model plant species in numerous research projects involving genome, molecular and evolutionary biology. In this review we describe the reasons why rice provides an excellent model system for centromere and heterochromatin research. In most multicellular eukaryotes, centromeres and heterochromatic domains contain long arrays of repetitive DNA elements that are recalcitrant to DNA sequencing. In contrast, three rice centromeres and the majority of the cytologically defined heterochromatin in the rice genome have been sequenced to high quality, providing an unparalleled resource compared to other model multicellular eukaryotes. Most importantly, active genes have been discovered in the functional domains of several rice centromeres. The centromeric genes and sequence resources provide an unprecedented opportunity to study function and evolution of centromeres and centromere-associated genes.     

HLA-DRB1~* 1501与我国北方汉族儿童结核病的易感性研究

为了研究中国北方儿童结核病与HLAⅠ类基因的关联,我们采用PCR-SSO方法检测了97例北方汉族结核患儿和91例正常对照的HLA-DRBl,DQAl,DQBl等位基因.发现中国北方汉族儿童结核病与HLA-DRBl·1501有显著关联.进一步比较DR分子结构发现β链第86位氨基酸对结核病的易感性可能有重要意义.     

阿尔茨海默病患者血清中抗淀粉样蛋白抗体的免疫耐受

目的:研究阿尔茨海默病(AD)血清中抗Aβ抗体与淀粉样蛋白结合的特性。方法:以AD患者和健康老人的血清作一抗,①用组织淀粉样斑块免疫反应(TAPIR)观察与Tg2576鼠脑内老年斑结合能力;②Western blot检测与Aβ42-GST融合蛋白的结合能力;③将Aβ42与PC12细胞培养,加入健康老人和AD患者的血清后,MTT法观察PC12细胞存活率。结果:AD患者的血清中抗Aβ抗体与成熟老年斑和Aβ42-GST融合蛋白的结合能力较弱;加入AD血清后,PC12细胞的A值较健康老人血清相比下降明显(P<0.01)。结论:AD血清中抗Aβ抗体对淀粉样蛋白可能存在着免疫耐受。     

异搏定对失血性休克犬肾脏的保护作用及其机制的研究

复制犬失血性休克模型。动物随机分为两组：失血对照组（ｎ＝５），失血＋异搏定组（ｎ＝６）。结果发现，异搏定治疗后肾脏组织内黄嘌呤氧化酶活性和丙二醛含量均较失血对照组明显降低，而锰－超氧化物歧化酶活性却显著高于失血对照组，肾脏组织电镜观察显示其超微结构损伤也较失血对照组轻。提示钙拮抗剂异搏定治疗失血性休克可以减轻肾脏损伤，其机理与改善内脏灌流，减少氧自由基生成有关。     

超声彩色脉搏波技术在定量评价2型糖尿病患者颈动脉弹性变化中的应用

目的 探讨超声彩色脉搏波(UFPWV)技术在定量评价2型糖尿病患者颈动脉血管管壁弹性变化中的应用价值。方法 回顾性研究。纳入2018年7月-2019年3月蚌埠医学院第一附属医院收治的97例2型糖尿病患者为观察组,其中男47例、女50例,年龄20~74(46.6±9.3)岁;根据颈动脉内中膜厚度(IMT)将观察组分为颈动脉粥样斑块组(A组)、颈动脉内中膜增厚组(B组)和颈动脉内中膜正常组(C组),依据下肢动脉有无斑块将C组分为下肢动脉斑块组(C1组)、下肢动脉无斑块组(C2组)。选取2017年12月-2018年12月在蚌埠医学院第一附属医院体检中心血糖及颈动脉IMT正常的健康体检者64人为对照组,其中男25人、女39人,年龄20~74(44.3±12.0)岁。运用UFPWV采集脉搏波速度 (PWV),计算颈动脉收缩早期PWV(PWV-BS)及收缩晚期PWV(PWV-ES),分析各项参数组间的差异。结果 观察组中,A组颈动脉PWV-BS、PWV-ES分别为(9.51±1.25)m/s、(10.79±1.64)m/s,B组分别为(8.47±0.91)m/s、(9.81±1.05)m/s,C组分别为(7.97±0.77)m/s、(9.07±0.74)m/s,对照组颈动脉PWV-BS、PWV-ES分别为(6.10±1.00)m/s、(7.40±1.20)m/s,A组、B组、C组及对照组间颈动脉PWV-BS、PWV-ES测量值依次降低,差异均有统计学意义(P值均<0.05)。C组中,C1组颈动脉PWV-BS、PWV-ES分别为(7.83±0.85)m/s、(8.82±0.59)m/s,C2组分别为(8.14±0.64)m/s、(9.34±0.79)m/s, C1组PWV-ES显著高于C2组,差异有统计学意义(t=3.402,P＜0.01),而两组间PWV-BS的差异无统计学意义(P>0.05)。结论 UFPWV技术可定量评价2型糖尿病患者颈动脉弹性变化,并可通过PWV-ES的改变评估颈动脉形态学正常的患者动脉粥样硬化的进展程度,对临床诊疗具有一定意义。