出、入肺血中ET-1、VEGF含量与慢性低氧性肺动脉高压的相关性研究

目的：观察间断性减压低氧大鼠出、入肺血血浆、肺组织匀浆和体循环动脉匀浆中内皮素-1（ET-1）的含量变化,以及出、入肺血血清中血管内皮生长因子（VEGF）的含量变化及其与低氧性肺动脉高压的关系。方法：建立间断性减压低氧模型,采用插管法分别测定左侧颈总动脉压力（CAP）、右心室平均压分别代表体循环压力和平均肺动脉压力（mPAP）,放射免疫测定法测定ET-1含量,双抗体夹心ABC—ELISA法测定VEGF含量。结果：①低氧2周组（H2）、低氧3周组（H3）大鼠平均肺动脉压力、右心肥厚指数（RV／LV＋S）均分别显著高于对照组,而各组平均颈动脉压力之间无明显变化（P〉0．05）。②对照组大鼠出肺血中ET含量比入肺血中低（P〈0．05）。H2、H3组大鼠出、入肺血中ET-1含量较对照组均明显增高（P〈0．01）,且H2、H3组大鼠出肺血中ET-1含量均高于入肺血中ET-1含量（P〈0．05）,刚好与对照组相反。H2、H3组大鼠肺组织匀浆中ET—1含量与对照组肺组织和低氧组体循环动脉组织匀浆比较,均明显增高（P〈0.01）,而各组体循环动脉组织匀浆中ET-1含量间无明显差异（P〉0．05）：③对照组大鼠出、入肺血中VEGF含量无明显差异（P〉0．05）,H2、H3组大鼠出肺血血清中VEGF含量较对照组明显增高（P〈0.01）。结论：在慢性低氧可使肺组织产生ET-1和VEGF增多,这可能是慢性肺动脉高压发生、发展的重要机制之一。肺动脉局部缩血管物质ET-1增高,而体循环动脉局部ET-1不增高。可能是长期慢性低氧可导致肺动脉高压的形成,却不发生高血压的机制之一。     

Gender Differences in the Effects of Prenatal Stress on Brain Development and Behaviour

An increased incidence of anxiety, depression and attention deficits in children has been linked to psychological stress during pregnancy. Subjection of a pregnant rat to stress at a time when the foetal limbic and hypothalamic pituitary adrenal (HPA) axes develop results in anxiogenic and depressive behaviour and learning and attention deficits in the offspring, which depend on its gender, intensity and timing of the maternal stress and behaviour being tested. Maternal stress increases corticosterone levels in the foetal brain, decreases foetal testosterone and brain aromatase activity in males, and alters brain catecholamine activity to that in females. Learning deficits, reductions in hippocampal neurogenesis, LTP and dendritic spine density in the prefrontal cortex are more readily seen in prenatally-stressed males, while anxiety, depression and increased response of the HPA axis to stress are more prevalent in females. Genders may differ in the sensitivity of developing brain areas to stress hormones. Special issue dedicated to Dr. Moussa Youdim.     

Cytogenetic effects of extremely low frequency magnetic field on Wistar rat bone marrow

In this study, the genotoxic and cytotoxic potential of extremely low frequency magnetic fields (ELF-MF) was investigated in Wistar rat tibial bone marrow cells, using the chromosomal aberration (CA) and micronucleus (MN) test systems. In addition to these test systems, we also investigated the mitotic index (MI), and the ratio of polychromatic erythrocytes (PCEs) to normochromatic erythrocytes (NCEs). Wistar rats were exposed to acute (1 day for 4 h) and long-term (4 h/day for 45 days) to a horizontal 50 Hz, 1 mT uniform magnetic field generated by a Helmholtz coil system. Mitomycin C (MMC, 2 mg/kg BW) was used as positive control. Results obtained by chromosome analysis do not show any statistically significant differences between the negative control and both acute and long-term ELF-MF exposed samples. When comparing the group mean CA of long-term exposure with the negative control and acute exposure, the group mean of the long-term exposed group was higher, but this was not statistically significant. However, the mean micronucleus frequency of the longer-term exposed group was considerably higher than the negative control and acutely exposed groups. This difference was statistically significant (p < 0.01). The results of the MI in bone marrow showed that the averages of both A-MF and L-MF groups significantly decreased when compared to those in the negative control (p < 0.001 and p < 0.01, respectively). No significant differences were found between the group mean MI of A-MF exposure with L-MF. We found that the average of PCEs/NCEs ratios of A-MF exposed group was significantly lower than the negative control and L-MF exposed groups (p < 0.001 and p < 0.01, respectively). In addition, the group mean of the PCEs/NCEs ratios of L-MF was significantly lower than negative control (p < 0.01). We also found that the MMC treated group showed higher the number of CA and the frequency of MN formation when compared to those in all other each groups (p-values of all each groups <0.01) and also MMC treated group showed lower MI and the PCEs/NCEs ratios when compared to those in all other each groups (p-values of all groups <0.01). These observations indicate the in vivo suspectibility of mammals to the genotoxicity potential of ELF-MF.     

Simultaneous analysis of tramadol, O-desmethyltramadol, and N-desmethyltramadol enantiomers in rat plasma by high-performance liquid chromatography-tandem mass spectrometry: application to pharmacokinetics

Tramadol (T) is available as a racemic mixture of (+)‐trans‐T and (−)‐trans‐T. The main metabolic pathways are O‐demethylation and N‐demethylation, producing trans‐O‐desmethyltramadol ( M1 ) and trans‐N‐desmethyltramadol ( M2 ) enantiomers, respectively. The analgesic effect of T is related to the opioid activity of (+)‐trans‐T and (+)‐ M1 and to the monoaminergic action of (+/−)‐trans‐T. This is the first study using tandem mass spectrometry as a detection system for the simultaneous analysis of trans‐T, M1 , and M2 enantiomers. The analytes were resolved on a Chiralpak® AD column using hexane:ethanol (95.5:4.5, v/v) plus 0.1% diethylamine as the mobile phase. The quantitation limits were 0.5 ng/ml for trans‐T and M1 and 0.1 ng/ml for M2 . The method developed and validated here was applied to a pharmacokinetic study in rats. Male Wistar rats (n = 6 at each time point) received a single oral dose of 20 mg/kg racemic trans‐T. Blood samples were collected up to 12 h after drug administration. The kinetic disposition of trans‐T and M2 was enantioselective (AUC_(+)/(−) ratio = 4.16 and 6.36, respectively). The direction and extent of enantioselectivity in the pharmacokinetics of trans‐T and M2 in rats were comparable to data previously reported for healthy volunteers, suggesting that rats are a suitable model for enantioselective studies of trans‐T pharmacokinetics. Chirality, 2011. © 2010 Wiley‐Liss, Inc.     

多次采血对Wistar大鼠脏器系数的影响

目的研究不同时间间隔经眼眶静脉丛多次采血后,对雄性Wistar大鼠重要脏器系数的影响。方法实验组分别间隔3 d、7 d、10 d,经眼眶静脉丛采血,每次采血1 mL,共采3次。对照组于实验组最后一次采血时采血一次,采血1 mL。每次采血前称量体重,于最后一次采血后将大鼠处死,取心脏、肝脏、肾脏、脾脏、胸腺,称量脏器重量,计算脏器系数。结果间隔3 d多次采血,大鼠的肝、肾系数差异具有显著性（P〈0.05）,间隔7 d、10 d多次采血,大鼠的各脏器系数差异无显著性。结论间隔3 d多次采血对大鼠的肝、肾系数有影响,间隔7 d、10 d多次采血对各脏器系数均无影响。     

SD大鼠胚胎-胎仔发育毒性试验的基础数据

目的 检测胚胎-胎仔发育毒性试验中SD大鼠妊娠期的体重、生殖功能指标及胎鼠的各项发育指标,为SD大鼠的发育毒性研究提供参考数据.方法 395只SD雌性大鼠,交配成功后,于妊娠第20天剖检孕鼠,检查孕鼠的内脏器官有无异常,称量子宫重量、窝重和胎盘重量,计数黄体数、着床数、活胎数、吸收胎数和死胎数.胎鼠共5272只,将一半胎鼠放人固定液中做内脏检查,另一半胎鼠进行骨骼检查,检查胎鼠外观、内脏和骨骼有无异常和变异.结果 和结论 建立SD大鼠胚胎-胎仔发育毒性试验中各项指标的数据库,求得各指标的正常值及标准差,95％的可信区间,为生殖毒性研究提供正常值的参考依据.     

近交系MIJ和HFJ大鼠部分生理数据测定和分析

目的测定近交系大鼠MIJ、HFJ和封闭群Wistar大鼠的脏器系数、体温、呼吸频率、肠管长度,观察两个近交系大鼠的生理表型。方法 采用常规方法对大鼠脏器系数、体温、呼吸频率及肠管长度进行测定,并对HFJ、MIJ、Wistar大鼠三者间进行比较。结果①体重:HFJ、MIJ、Wistar大鼠同性别间比较差异无显著性。②脏器系数:HFJ与Wistar大鼠雄性间心脏、肺,雌性间子宫、肝;MIJ与Wistar大鼠雄性间肺、脾,雌性间脑、脾,差异均有显著性。HFJ与MIJ大鼠雄性间脑,雌性间脑和脾差异有显著性。HFJ大鼠不同性别间肝、脑、眼球差异有显著性。MIJ大鼠不同性别间,脑、心脏、肾、肺、脾和眼球差异均有显著性。③体温:HFJ雌性大鼠明显高于Wistar雌性,雄性间差异无显著性。HFJ大鼠雌性高于雄性,差异有显著性。④呼吸频率:HFJ雌性大鼠低于同性Wistar大鼠,MIJ大鼠雌性和雄性均高于同性别Wistar大鼠,差异有显著性。⑤肠管长度:HFJ与Wistar同性别间比较,肠管总长和小肠差异有显著性。MIJ与Wistar大鼠雄性间肠管总长、大肠、小肠、盲肠差异均有显著性,雌性间肠管总长、小肠、盲肠差异有显著性。HFJ与MIJ大鼠同性别间差异均无显著性,不同性别的HFJ和MIJ的肠管总长、大肠和小肠差异有显著性。结论 MIJ和HFJ近交系大鼠的脏器系数、体温、呼吸频率、肠管长度都各有其独特的生理概貌。     

羊骨胶原肽对青春期大鼠催乳素和促黄体生成素分泌脉冲的影响

目的研究羊骨胶原肽(sheep bone collagen peptide,SBCP)对类固醇诱导的去卵巢大鼠催乳素(pro-lactin,PRL)和促黄体生成素(luteinizing hormone,LH)分泌脉冲的影响。方法 6周龄子宫颈未开口的青春期SD大鼠实施双侧卵巢摘除手术,康复1周或3周后以类固醇替代方法诱导PRL和LH脉冲,处理组同时按1000 mg/(kg.d)的剂量以SBCP灌胃,通过颈导管采集血样,利用放射免疫技术测定各组大鼠外周血中的LH和PRL浓度。结果对于术后康复1周的大鼠,SBCP对LH脉冲振幅起到增强作用,而对PRL脉冲没有影响;对于术后康复3周的大鼠,SBCP对LH和PRL脉冲振幅均表现为降低作用,但卵巢摘除后立即给予SBCP可减弱这种降低作用。结论雌激素和孕激素替代注射的同时,补充羊骨胶原肽,不仅仍可诱导LH和PRL脉冲的产生,还可预防由于卵巢摘除带来的骨代谢紊乱,免疫力低下等不良影响,因而是对现有类固醇替代方法的改良。