大鼠液压冲击脑损伤后bFGF及其受体FGFR1的表达

目的观察脑损伤后碱性成纤维细胞生长因子(bFGF)及其受体FGFR1的表达及其时序性变化,探讨脑损伤的分子机制及法医学脑损伤时间推断。方法用免疫组织化学技术观察大鼠侧位中度液压冲击脑损伤后bFGF及FGFR1蛋白在伤后不同时间(30min,1,3,6,12h,1,3,7d)的表达情况,以正常大鼠及手术大鼠作为对照。结果正常对照组和手术对照组大鼠脑组织内有低水平的bFGF和FGFR1表达。脑冲击伤后6h,大脑皮层和脑干bFGF和FGFR1蛋白表达开始显著增加,1～3d达高峰,7d时已有所下降;海马冲击后3h即开始增加,1d达峰值,此后逐渐下降,7d时恢复正常。结论脑损伤可诱导bFGF/FGFR1的表达,提示机体对脑损伤存在自身保护机制,其表达的时序性改变可望用于法医学脑损伤时间推断。     

谷氨酸受体基因单核苷酸多态性与精神分裂症的关联

谷氨酸是人类神经系统中重要的兴奋性神经递质,通过与受体结合发挥生物学作用.当编码受体的基因异常时,可能导致精神疾病发生.本文通过回顾相关研究,发现诸如GRIN1、GRIN2B、GRM3等受体基因上的rs11146020、366C/G、rs1468412与精神分裂症相关联;同时也存在矛盾的研究结果,表明精神分裂症可能为多因素、多位点、多基因复杂遗传疾病.部分位点如GRIN2B上的366C/G、2664C/T,GRIK2上的rs1408766(C/T)的遗传多态性较好,可能成为法医学个人识别与亲权鉴定的新指标.该领域研究在司法精神病的鉴定工作中可能具有潜在的意义.     

传染性腔上囊炎疫苗免疫鸡TLR7基因表达的动态变化

给11日龄雏鸡分别口服接种鸡传染性腔上囊炎(IBD)弱毒疫苗(法贝灵,IBD-Blen)1和3头份后,于不同时间采集脾和腔上囊组织,分离纯化淋巴细胞,常规方法抽提总RNA,以鸡β-actin基因为内参,采用半定量RT-PCR法检测两种组织中鸡Toll样受体7(ChTLR7)基因的表达动态。结果显示,接种IBD弱毒疫苗前,试验鸡脾和腔上囊组织中均有ChTLR7的微量表达,疫苗接种后第7 h,脾中ChTLR7 mRNA的表达开始显著上调,至接种后第12 h达峰值,此后迅速下降,至第130 h时降至疫苗接种前的水平;而腔上囊组织中ChTLR7 mRNA的表达自接种后第12 h开始增加,第24 h时达峰值,随后迅速下降,约72 h后恢复至疫苗接种前水平。表明ChTLR7可能参与了IBDV感染早期的天然免疫反应过程。     

CCK受体基因多态性及与部分精神疾病症状的相关性

胆囊收缩素(CCK)不仅存在于消化系统,而且还广泛存在于中枢及外周神经系统,并以神经递质的形式通过其受体(CCK-R)发挥着重要的生理作用。CCK-R有两种类型,CCK-AR和CCK-BR。CCK-R基因具有遗传多态性,并通过影响或改变CCK对中枢神经系统的作用强度而与酒精中毒、精神分裂症、恐慌症等人类精神疾病密切相关。CCK-R基因遗传多态性的研究可能为法医学个人识别与亲权鉴定新提供新的遗传标记及为司法精神病鉴定提供参考性遗传学指标。     

荷斯坦乳牛乳腺和乳腺上皮细胞中Toll样受体及辅助因子编码基因的检测

参照牛TLR4、TLR2、CD14、MD-2基因序列设计了相应基因的引物。采用RT-PCR技术检测了体外培养的荷斯坦乳牛乳腺和乳腺上皮细胞中Toll样受体TLR4、TLR2及辅助因子CD14、MD-2基因。结果显示,乳腺上皮细胞中存在TLR4、TLR2、CD14和MD-2四个基因的表达,而乳腺中除MD-2未检测到外,其余3个基因均扩增成功。说明该受体及辅助因子可能参与了乳腺的先天性免疫防御。该研究为探讨乳腺的先天性免疫及乳腺上皮细胞在乳腺先天性免疫中的作用奠定了基础。     

阿维菌素对鸽脑组织GABAA受体结合作用的影响

在试验组日粮中按40 mg/kg添加阿维菌素(AVM),对照组饲喂不添加AVM的常规日粮,利用3H-蝇蕈醇(3H-muscimol)与鸽脑组织γ-氨基丁酸(GABA)均能与GABAA受体结合的特性,应用放射免疫法测得3H-蝇蕈醇与王鸽大脑GABAA受体结合的平衡解离常数(kd)和最大结合量(Bmax)分别为(44.62±2.07)nmol/L和(3.31±0.10)pmol/mg。结果表明,AVM可使3H-muscimol与王鸽大脑组织GABAA受体结合量增大,AVM可促进GABA的释放,增强GABA的抑制作用。     

健胎液对模型小鼠着床期子宫内膜容受性的影响

目的:研究健胎液对胚泡着床障碍小鼠着床期子宫内膜容受性的影响。方法:于妊娠第4天9∶00利用米非司酮建立胚泡着床障碍小鼠模型,予健胎液进行干预,于妊娠第4天21∶00处死小鼠,观察小鼠胚泡着床率及平均着床胚泡数,采用放免法检测血清及子宫组织雌二醇、孕酮的含量,采用逆转录聚合酶链式反应(RT-PCR)检测子宫ERmRNA、PRmRNA表达。结果:与模型组相比,中药组着床率和平均着床胚胎数均显著升高,与对照组无显著差异;模型组子宫内膜发育不良,中药组子宫内膜的发育与正常组相似;3组血清及子宫组织的雌二醇和孕酮的含量无显著改变;中药组子宫ER mRNA、PR mRNA表达均较模型组显著提高,与正常组比较差异无显著性。结论:健胎液通过促进子宫内膜发育,调节胚泡着床障碍小鼠子宫组织ER、PR基因的表达,改善子宫内膜容受性,利于胚泡着床。     

Synthesis,structure, in vitro pharmacology,and in vivo activity of trans-3,4-dichloro-N-[[1-(dimethylamino)-4-phenylcyclohexyl]methyl]-benzamide (AP01; 4-phenyl-AH-7921), a novel mixed μ-/κ-opioid

Analogs of non-fentanyl novel synthetic opioids (NSO) with modifications that fall outside of established structure–activity relationships (SARs) for that class of drugs create the question whether or not it should be considered an analog, as defined by 21 U.S.C. §802(32)(A), which is important for its inclusion in the US system of drug scheduling. AH-7921 is a US Schedule I drug and an example of the 1-benzamidomethyl-1-cyclohexyldialkylamine class of NSO. The SARs regarding substitution of the central cyclohexyl ring have not been well characterized in the literature. Therefore, in order to expand the SAR surrounding AH-7921 analogs, trans-3,4-dichloro-N-[[1-(dimethylamino)-4-phenylcyclohexyl]methyl]-benzamide (AP01; 4-phenyl-AH-7921) has been synthesized, analytically characterized, and tested in vitro and in vivo pharmacologically. Using methods described in the original patents for this class of NSO, it was found that the single trans geometric isomer was obtained. The proton nuclear magnetic resonance, mass spectrum, infrared spectrum, and Raman spectrum are reported along with the melting point of the hydrochloride salt. In vitro binding to a battery of 43 central nervous system receptors showed it to be a high-affinity μ-opioid receptor (MOR) and κ-opioid receptor (KOR) ligand (60 nM and 34 nM, respectively). AP01 also had a 4 nM affinity for the serotonin transporter (SERT), which is a higher level of potency at this receptor than most other opioids. In rats, it exhibited antinociception in the acetic acid writhing test. Therefore, the 4-phenyl modification results in an active NSO, but carries with it potential toxicities beyond those expected for currently approved opioid drugs.     

大麻素受体在皮肤创伤愈合过程中的作用

创伤愈合是机体通过自身的再生能力,恢复机体表面的连续性和完整性,维护机体内环境稳定所进行的一系列修复活动。存在于皮肤的内源性大麻素受体参与生长、增殖、分化以及凋亡,调控炎症和纤维化过程。本文针对大麻素受体在创伤愈合过程中的作用,对研究文献进行综述,希望能对相关研究和应用提供参考。     

GABA Receptors,Alcohol Dependence and Criminal Behavior

The aim of this study was to analyze the connection between alcohol dependence and criminal behavior by an integrated genetic–environmental approach. The research, structured as a case–control study, examined 186 alcohol‐dependent males; group 1 (N = 47 convicted subjects) was compared with group 2 (N = 139 no previous criminal records). Genetic results were innovative, highlighting differences in genotype distribution (p = 0.0067) in group 1 for single‐nucleotide polymorphism rs 3780428, located in the intronic region of subunit 2 of the GABA B receptor gene (GABBR2). Some environmental factors (e.g., grade repetition) were associated with criminal behavior; others (e.g., attendance at Alcoholics Anonymous) were inversely related to convictions. The concomitant presence of the genetic and environmental factors found to be associated with the condition of alcohol‐dependent inmate showed a 4‐fold increase in the risk of antisocial behavior. The results need to be replicated on a larger population to develop new preventive and therapeutic proposals.