鼠骨关节炎动物模型建立的现状

骨关节炎(osteoarthritis，OA)是临床上常见的疾病。探索骨关节炎动物模型的建立方法，是研究其病因和治疗方法的重要课题之一。鼠是一种理想的动物，所用的方法有关节内手术、关节内注射、关节外手术等，各种方法都有自己的长处和不足。本文就鼠骨关节炎动物模型的建立方法、模型特点及其应用等方面进行综述。     

Effect of omeprazole on the anticoagulant activity and the pharmacokinetics of warfarin enantiomers in rats

The effect of the proton pump inhibitor omeprazole on the anticoagulation and the pharmacokinetics of warfarin enantiomers was studied in rats. Omeprazole given intraperitoneally in a daily dose of 0.67 mg/kg over 8 days had no significant effect on the absorption, distribution and the total serum clearance values of the S- and R-enantiomers of warfarin. Omeprazole did not affect the pre-treatment baseline blood coagulation and the in vitro rat serum protein binding of warfarin enantiomers. In vitro study with rat liver microsomes showed that omeprazole had an inhibitory effect on the hydroxylation of warfarin enantiomers. Results obtained from in vivo urinary excretion study revealed that omeprazole inhibited the formation clearance of both S- and R-form oxidative metabolites, but increased that of the overall reductive metabolites, and the renal clearance of S- and R-enantiomers, of warfarin. As a consequence, the total serum clearance values for warfarin enantiomers remained unchanged and the hypoprothrombinaemic response produced by warfarin was not affected.     

Acute tolerance to ethanol using drug discrimination and open-field procedures in rats

This study examined the phenomenon of acute tolerance to ethanol (ETOH) using drug discrimination learning (DDL), and open-field (OF) procedures. In DDL, rats were trained to discriminate between ETOH (1.2 g/kg) and saline. Doses of ETOH lower (0.6 and 0.9 g/kg), or higher (1.8 and 2.4 g/kg) than the training dose were tested to examine possible influence of ETOH pretreatment doses on the expression of acute tolerance. To assess concentrations of ETOH in the organism, a rebreathed air procedure was used. Equal concentrations after different ETOH doses were achieved by postponing the tests until sufficient time had elapsed. Only doses of ETOH higher than the training dose produced acute tolerance in the DDL procedure. For the response-time data no acute tolerance was observed. In the OF experiment, the occurrence of acute tolerance was examined for different spontaneous behaviours in drug-naive animals. At equal ETOH concentrations, the group examined during the descending phase of intoxication (1.8 g/kg, 60 min post-injection), reared significantly more than the group tested during the ascending phase (1.5 g/kg, 10 min post-injection). Other OF behaviours did not differ significantly between the two time intervals. Thus, it is suggested that acute tolerance is seen both in ETOH naive and in ETOH pre-exposed rats. However, in DDL acute tolerance was observed only when doses higher than the training dose of ETOH were evaluated.     

胎脑组织移植对额叶皮质损伤后基底前脑胆碱能神经元变性的影响

目的：观察胎脑组织移植对额叶皮质损伤后大鼠基底前脑胆碱能神经元变性的影响。方法：用外科手术破坏大鼠双侧额叶皮质8d后，将胎脑组织移植到预制脑创腔内。3个月后，用Y型迷宫检测动物的学习、记忆机能，用组织化学方法检测基底前脑含乙酰胆碱脂酶（AChE)活性神经元，并与对照组比较。结果：双侧额叶皮质损伤后动物的学习、记忆能力明显下降，基底前脑胆碱能神经元明显减少，与正常组比较，差异有显著性（P＜0．05）和差异有极显著性（P＜0．01）。胎脑组织移植后3个月，双侧额叶皮质受损动物的学习、记忆机能明显改善，基底前脑胆碱能神经元数量明显增加，与对照组比较，差异有性（P＜0．05）。结论：胎脑组织移植可有效地预防双侧额叶皮质受损大鼠的学习、记忆机能的下降和基底前脑胆碱能神经元数量的减少。     

EGCG对大鼠肾脏缺血再灌注损伤的保护作用

目的研究表绿茶活性成分没食子儿茶素-3-没食子酸酯（epigallocatechin gallate，EGCG）对大鼠肾脏缺血再灌注损伤是否具有保护作用。方法将12只Lewis大鼠随机分为2组：（1）实验组大鼠7只，于肾缺血后的再灌注期将10mg／kg的EGCG置于2ml生理盐水中静脉注射；（2）对照组大鼠5只，于肾缺血后的再灌注期静脉注射2ml生理盐水。2h后处死动物，收集血液和肾脏标本，行血肌酐（Cr）、尿素氮（BUN）、肾组织超氧化物歧化酶（SOD）和脂质过氧化产物丙二醛（MDA）含量测定，并进行组织病理和超微病理检查。结果实验组大鼠血Cr和BUN水平明显低于对照组（P〈0.05），肾组织中SOD活性较对照组明显升高（P〈0．01），肾组织脂质过氧化产物MDA的含量较对照组明显降低（P〈0．01）。病理学检测表明实验组大鼠肾小管周围毛细血管内未见淤血，肾小管上皮细胞变性及线粒体的损伤减轻。结论EGCG对大鼠肾脏缺血再灌注损伤具有保护作用。     

心率功率谱分析影响呼吸性窦性心律不齐的因素

用大鼠心电R波峰触发心率计,心率信号经电子计算机采样后进行快速富里叶(FFT)变换,得出心率变异的功率谱分布。以心率功率谱中高频峰密度作为呼吸性窦性心律不齐的客观指标,定量观察了肌松、断双侧迷走神经、开胸及不同人工呼吸频率对大鼠呼吸性窦性心律不齐的影响。结果表明迷走神经活动引起的呼吸性窦性心律不齐占整个呼吸性窦性心律不齐的72%,因此心率功率谱分析有可能成为无创检测心迷走神经功能状态的方法。     

IL－10对大鼠佐剂性关节炎的治疗及免疫机理探讨

形成佐剂性关节炎（ＡＡ）的动物模型，研究ＩＬ－１０的抗炎作用及其机理。结果表明，经腹腔注射ＩＬ－１０后能改善ＡＡ大鼠病情，用ＩＬ－１０治疗取得显效后，ＡＡ大鼠血清及关节液内炎症细胞因子ＩＬ－１，６，８，ＴＮＦ水平均明显下降，腹腔巨噬细胞和脾淋巴细胞分泌细胞因子的能力均受到抑制。表明ＩＬ－１０是通过抑制炎症细胞因子的产生而发挥治疗作用的。此项研究为用ＩＬ－１０治疗人风湿性关节炎（ＲＡ）等难治性炎症性疾病提供了理论和实验依据     

Age-Specific Effects of Baclofen on Pentylenetetrazol-Induced Seizures in Developing Rats

Summary: Purpose : To determine whether seizures have age-specific features, we studied the role of γ-aminobutyric acid, (GABAB) transmission in rats of various ages (9, 15, 30, and 60 postnatal days). Methods: We used a GABA, receptor agonist baclofen (2 or 5 mg/kg intraperitoneally, i.p.) and a GABA_B receptor antagonist CGP 35348 (100 or 600 mg/kg i.p.) in the pentylenetetrazol (PTZ)-induced model of clonic and tonic-clonic seizures (100 mg/kg subcutaneously, s.c.).
Results : Whereas baclofen was anticonvulsant and CGP 35348 proconvulsant in most animals, there were distinct age-related differences in the effectiveness of these drugs and the antagonist had some anticonvulsant activity in adults. Furthermore, the two drugs acting at GABA_B receptors had a different profile of action in clonic seizures as compared with tonic-clonic seizures.
Conclusions : The differences in the age-specific action of the GABA_B agonist and antagonist suggest that different GABA_B receptor subsets may mediate the drug effects. The results indicate that putative antiepileptic drugs (AEDs) must be tested during development because it may not be possible to extrapolate age-specific anticonvulsant effects from studies in adult animals.     

Substitution of the 5-HT1 agonist trifluoromethylphenylpiperazine (TFMPP) for the discriminative stimulus effects of ethanol: effect of training dose

The role of the ethanol training dose on the ability of the selective 5-HT¹ agonist TFMPP (m-trifluoromethylphenylpiperazine) to produce ethanol-like discriminative stimulus effects was evaluated in three groups of rats trained to discriminate 1.0 g/kg (n=5), 1.5 g/kg (n=6) or 2.0 g/kg (n=7) ethanol (IG) from water using a two-lever procedure with food reinforcement available under a fixed ratio 20 (FR 20) schedule. Ethanol generalization gradients were comparable in the three groups, indicating few potency differences in the ethanol stimulus across training dose. However, the ability of TFMPP (0.1–1.7 mg/kg; IP) to substitute for ethanol was dependent on the training dose. TFMPP resulted in partial substitution in the 1.0 g/kg group, complete substitution for 1.5 g/kg group and no substitution in the 2.0 g/kg ethanol training group. The results indicate a serotonergic component to the discriminative stimulus effects of an intermediate dose of ethanol that is not prominent as the dose of ethanol is raised. These data add further support for the hypothesis that ethanol produces a mixed discriminative cue, the components of which are not uniformly amplified when the dose of ethanol is increased.     

Behavioural specificity of 8-OH-DPAT-induced feeding

8-Hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) has been reported to increase food intake. This effect was confirmed in rats consuming plain or sweetened wet mash. However, the consumption of a 35% sucrose solution or of a range of other flavoured liquids was enhanced marginally if at all by a single low dose of 8-OH-DPAT, and the drug actually decreased the consumption of a high protein liquid diet. 8-OH-DPAT did, however, increase gnawing on a wooden block. These results suggest that 8-OH-DPAT-induced hyperphagia may to some extent be secondary to the elicitation of chewing behaviour. 8-OH-DPAT also caused certain other behavioural changes, including a suppression of grooming.