Effects of short- and long-acting dopamine agonists on sensitized dopaminergic neurotransmission in rats with unilateral 6-OHDA lesions

The effects of short and long-acting dopamine agonists on sensitized dopaminergic transmission in an animal model of Parkinson's disease were investigated. Rats with 6-hydroxydopamine (6-OHDA) lesions of the left nigrostriatal dopaminergic pathway were pre-exposed i.p. to 50 mg/kg methyl levodopa for 10 days. After a 7-day withdrawal period, these animals were treated with saline i.p., 0.05 mg/kg apomorphine s.c., or 0.5 mg/kg cabergoline i.p., once daily for 7 days. On the 8th day, rats in each treatment group received a challenge dose of 0.05 mg/kg apomorphine or saline s.c. The temporal changes in the number of rotations away from the 6-OHDA lesion side were evaluated after the challenge. The apomorphine challenge increased the number of rotations more markedly in the apomorphine pretreated rats than in the other pretreatment groups. In cabergoline pretreated rats, the number of rotations was significantly lower than that of saline-pretreated animals. Pretreatment with saline did not alter the apomorphine sensitivity of rotational behavior. These findings suggest that the repeated administration of long-acting dopamine agonists may reduce sensitized dopaminergic transmission in dopamine-depleted rats, whereas short-acting ones may further enhance sensitization of the transmission process.     

Permanent sterility in the male rat after a single oral dose of pipecolinomethyl-hydroxyindane

A single oral dose (150 mg/kg) of DL-6-(N-alpha-pipecolinomethyl)-5-hydroxy-indane maleate dissoved in distilled water was administered to Sprague-Dawley male rats living under controlled conditions. After dosage the male rats cohabited with female rats which were replaced weekly. The incidence of pregnancy was determined for 20 weeks. The male rats were then killed and the testes examined histologically. Results showed subnormal fertility at the 3rd and 4th week, sterility at the 5th week. Sterility persisted until Week 20. Histological evidence showed absence of spermatogenic cells in treated rats with no signs of regeneration.     

Long-term intake of egg white hydrolysate attenuates the development of hypertension in spontaneously hypertensive rats

This paper evaluates the effect of the long-term intake of a hydrolysate of egg white with pepsin (HEW), with a potent angiotensin converting enzyme inhibitory activity, on the development of hypertension of spontaneously hypertensive rats (SHR). After being weaned, male 3-week-old SHR were randomly divided into five groups that were given until the 20th week of life the following drinking fluids: (1) tap water, (2) non-treated egg white 1 g/kg/day, (3) captopril 100 mg/kg/day, (4) HEW 0.5 g/kg/day, and (5) HEW 1 g/kg/day. From the 20th to 25th week of life, animals from all groups were given tap water. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured weekly in the rats, from the 6th to 25th week of life, by the tail cuff method. Development of hypertension was attenuated in the groups treated with captopril and HEW (P<0.001 vs. the group that drunk tap water). At the 20th week of life, the arterial blood pressure values of the different groups of rats were: tap water (SBP = 219.5 +/- 5.7, DBP = 167 +/- 3.7), non-treated egg white (SBP = 206.4 +/- 1.43, DBP = 166.4 +/- 4.9), captopril (SBP = 131.7 +/- 2.74, DBP = 91.5 +/- 1.62), HEW 0.5 g/kg/day (SBP = 182.9 +/- 4.64, DBP = 127.5 +/- 2.1) and HEW 1 g/kg/day (SBP = 177.7 +/- 4.72, DBP = 120.1 +/- 2.4). SBP and DBP increased in the treated SHR when the corresponding antihypertensive treatment was removed. In spite of this, SBP remained lower in the SHR that had received captopril and HEW than in the SHR of the control groups (P<0.05). The present results suggest that HEW could be used as a functional food with antihypertensive activity.     

阿霉素肾病大鼠尿液糖胺聚糖与尿液蛋白含量的相关性

目的探讨阿霉素肾病大鼠疾病进展过程中尿液糖胺聚糖含量的变化及其与尿蛋白的关系。方法采用一次性尾静脉注射阿霉素6mg/kg制作肾病综合征大鼠模型,第1、2、3、4、6周分别收集大鼠24h尿液测定尿糖胺聚糖和尿蛋白含量。43d后结束实验取血及肾脏,检测血生化,观察肾组织病理改变。结果第2、3、4、6周与正常对照组比较,阿霉素肾病大鼠24h尿蛋白排泄量呈进行性明显上升趋势;造模43d后模型组血清白蛋白含量显著下降,总胆固醇和甘油三酯含量显著升高,肾组织病理所见,模型组肾小球系膜区见中度至重度的系膜细胞增殖及基质增生。从第3周开始阿霉素肾病大鼠尿糖胺聚糖浓度显著高于正常组,且与24h尿蛋白排泄量呈正相关关系。第6周尿糖胺聚糖浓度与血清白蛋白浓度负相关,与甘油三酯浓度正相关。结论阿霉素肾病综合征大鼠尿液中糖胺聚糖浓度升高,并与24h尿蛋白排泄、血清白蛋白、甘油三酯浓度显著相关。     

Changes in hypothalamic noradrenaline and 5-hydroxytryptamine levels during the development of warm- and cold-adaptation in the rat

Hypothalamic 5-hydroxytryptamine (5-HT) and noradrenaline (NA) as well as plasma corticosterone levels were studied in male rats after 1, 2, 4 and 6 weeks of exposure to 4--7 or 30--31 degrees C. An increase of the NA concentration and a decrease of the 5-HT level was observed after the first week in both cold and warm environment together with an increase of plasma corticosterone levels in both groups. NA, 5-HT and plasma corticosterone levels returned to normal in cold-exposed animals by the 6th week whereas in warm-acclimated rats NA and corticosterone levels regained their initial values and 5-HT concentrations remained low. Changes by the end of the first week of exposure may result from the thermal stress. The low 5-HT levels of warm-adapted animals at the end of the 6th week were probably secondary to the process of adaptation.     

肝癌大鼠异常凝血酶原的研究

用灵敏的凝血酶原蛇毒激活测定法,观察二乙基亚硝胺诱发大鼠肝癌过程中,血浆异常凝血酶原及肝组织内凝血酶原前体含量的变化。血浆异常凝血酶原从诱癌第4周开始持续上升至第13周;第15周有所下降,第20周又开始回升。而在此过程中,肝组织内凝血酶原前体含量变化不明显,而在诱癌20周的肝癌结节内,凝血酶原前体显著堆积。同时,还研究了肝再生过程中大鼠血桨异常凝血酶原及肝内凝血酶原前体的变化。华法令处理的大鼠作为阳性对照。     

Bax蛋白在大鼠肝癌发生过程中的表达和意义

通过动态观察Bax蛋白在实验性大鼠肝癌发生过程中肝细胞的表达,探讨Bax蛋白与肝癌发生的关系及其生物学意义。用DEN饲喂大鼠,分别于第4、8、12、16、18周处死大鼠,取其肝脏,石蜡切片,ABC法免疫组织化染色。结果显示：正常成年大鼠肝细胞均有中等程度Bax蛋白表达。至诱癌第4周大鼠肝小叶内有少数肝细胞呈Bax蛋白免疫阳性反应,随诱癌发展进程,呈Bax蛋白免疫阳性反应肝细胞进一步减少,第12周,只可见肝细胞增生结节的多数肝细胞呈Bax蛋白免疫阳性反应。诱癌晚期（第18周）,癌结节内肝癌细胞均呈Bax免疫反应阳性,其强度较正常肝细胞明显增强,Bax蛋白免疫反应产物为胞质内粗大的棕褐色颗粒。部争肝细胞胞质和胞膜均呈阳性,肝癌细胞最为常见。结果表明：Bax蛋白表达减少或缺失是肝癌发生过程中的早期事件,可能参与肝癌的启动过程。     

Enhancement of reserpine-elicited dopaminergic supersensitivity by repeated treatment with apomorphine and alpha-methyl-p-tyrosine.

Pretreatment of rats with reserpine 5 mg/Kg/day for 2 days elicits an enhanced stereotyped response following injection of apomorphine or amphetamine which persists through the 17th day. Since apomorphine acts as a direct postsynaptic receptor agonist in dopaminergic neurons this effect may represent a postsynaptic supersensitivity. In an attempt to prevent the development of supersensitivity apomorphine was administered repeatedly during the reserpinization period. Contrary to expectations a further enhancement of supersensitivity was seen when animals were challenged days later with apomorphine. This may be the result of presynaptic dopamine-synthesis-inhibition following apomorphine. Apomorphine-induced enhancement of reserpine supersensitivity was not seen in animals challenged with amphetamine. Alpha-methyl-para-tyrosine, but not scopolamine, repeatedly administered during the reserpinization mimics the effect of apomorphine, supporting the concept that the potentiating effects of apomorphine are mediated presynaptically. Furthermore it is suggested that the direct presynaptic action of apomorphine, and not that mediated via cholinergic interneurons, is operant in the development of enhanced supersensitivity.     

The characteristics of cholinesterase distribution in the development of the human and mammalian brains]

Histochemical studies have been made on the distribution of acetyl- and butyrylcholinesterases (ACHE and BCHE) in various parts of the human and rat brain. Statistical analysis showed that at the 8th week, the highest ACHE activity in the human foetus is observed in the intermediate and plexiform layers of the cerebral cortex. The highest BCHE activity was found in the ependymal layer of various cerebral regions. High BCHE and ACHE activities were noted in the dorsal thalamus and epithalamus. In 10-week human foetuses, total high level of ACHE and BCHE was revealed in various nuclei of the thalamus and subcortical structures of the forebrain (Meynert nucleus, nucleus caudatum). In rats, the highest ACHE activity at the 14th day of prenatal life was found only in subcortical structures of the forebrain. Accumulation of BCHE activity in some of the thalamic nuclei of rats begins at the 10-17th day of postnatal life.     

Effect of social isolation on 24-h pattern of stress hormones and leptin in rats

This work analyzes the effect of social isolation of growing male rats on 24-h changes of plasma prolactin, growth hormone, ACTH and leptin, and on plasma and adrenal corticosterone concentrations. At 35 days of life, rats were either individually caged or kept in groups (6-8 animals per cage) under a 12:12 h light/dark schedule (lights on at 08:00 h). A significant arrest of body weight gain regardless of unchanged daily food intake was found in isolated rats after 2 weeks of isolation. On the 4th week, rats were killed at 6 time intervals during a 24-h cycle, beginning at 09:00 h. In isolated rats the 24-h pattern of all parameters tested became distorted, as assessed by Cosinor analysis. When analyzed as a main factor in a factorial analysis of variance, isolation decreased plasma prolactin and growth hormone, increased plasma leptin and corticosterone while decreased adrenal corticosterone. Plasma corticosterone levels correlated significantly with plasma ACTH and with adrenal corticosterone levels in group-caged rats only. These changes can be attributed to an effect of mild stress on the endogenous clock that modulates the circadian hormone release.     

Effect of group and isolated rearing of white rats on their resistance to exposure to emotional stress]

The influence of isolated vs. group breeding on the sensitivity of higher nervous and vegetative functions to chronic stress effects was studied in 50 albino random-bred male rats. It has been found that group breeding of the animals (ten specimens in each cage) from the 12th to the 30th week of their life enhances their resistance to external stress factors which begin to take effect from the 17th week on. The effect is linked to the positive emotions produced by mutual contacts among the animals and their intensified motor activity. Isolated breeding of the rats (beginning with the 17th week of their life) makes them vulnerable to the action of stress situations. By the end of the investigation they exhibit clear symptoms of an early stage of neurogenic hypertension. The isolation evidently sets up a negative emotional background, reduces drastically the motor activity and lowers the animals resistance to extreme environmental influences.     

糖尿病对大鼠骨折愈合影响的实验研究

目的:观察糖尿病大鼠的骨折愈合过程,探讨糖尿病影响大鼠骨折愈合的可能的机制,为临床实践提供理论依据。方法:雄性Wister大鼠140只,随机分成二组,每组70只,A组为糖尿病骨折组;B组为非糖尿病骨折组。建立糖尿病动物模型后,无菌条件下在各组大鼠胫骨中点用手术方法制成骨折模型。术后1周、2周、4周、6周、8周各时间点进行X线检查,观察骨折愈合情况。术后1周、2周、3周、4周、6周、8周分别用ELISA法检测血清中IGF-1含量。分别在1、2、4、6、8周各时间点观察5只大鼠骨痂生长情况并取骨折断端组织行HE染色光镜观察。术后4周、6周、8周每组处死10只大鼠留取双侧胫骨标本,冷冻保存后集中进行生物力学检测。结果:1、大体标本观察结果:各时间点A组骨痂生长减缓延迟。2、X线结果:A组骨折愈合质量在各时间点均明显低于B组。3、生物力学测定结果:4周、6周、8周个时间点A组骨折处骨痂的机械强度均明显低于B组。4、组织学染色显示:术后各时间点1、2、4、6、8周A组与B组相比骨折处局部骨痂成熟延迟并且软骨细胞肥大。5、血清IGF-1含量测定:A组大鼠血清中IGF-1含量低于B组,且高峰延迟1周。结论:1.患有糖尿病后大鼠骨折愈合质量差,比较容易出现愈合延迟甚至不愈合;2.患有糖尿病的大鼠骨折后血清中的IGF-1表达明显低于对照组,且高峰推迟1周。     

二乙基亚硝胺诱导大鼠肝癌组织CLDN1基因表达及其甲基化

目的探讨二乙基亚硝胺（diethylnitrosamine,DEN）诱导大鼠肝癌发生中肝癌组织CLDN1基因表达及其启动子甲基化的规律。方法65只雄性Wistar大鼠随机选择40只作为模型组,其余作为正常组。模型组在1-12周饮用含DEN80mg／L的饮水以诱癌（每日8mg／kg）,各组在造模过程的第4周、8周、12周、16周随机5只取肝,第20周剩余大鼠取肝,应用RT-PCR方法检测肝组织CLDN1mRNA的表达,应用MSP法检测肝组织CLDN1启动子甲基化和非甲基化。结果模型大鼠病死率为10％（4／40）,正常组无死亡。至第20周,成瘤率达到100％。RT—PCR显示,与正常组比较,模型组在16周和20周CLDN1 mRNA表达下调（P〈0．05）,其他各周两组差异不显著。MSP结果表明,模型组肝组织CLDN1甲基化率达77．78％,而正常肝组织甲基化率为24％,两者比较差异有显著性（P〈0．01）。结论CLDN1启动子甲基化及CLDN1基因表达下调与大鼠肝癌病变相关,对其机制值得进一步深入研究。     

Relationship between bound and free amino acids in the brain of growing rats]

Total pool of glutamate, glutamine and GABA in the hemispheres increases during postnatal life of rats, the increase being due to that in free and bound forms of amino acids. In the cerebellum of 1-day rats, the content of free and bound glu, gln asp, GABA, bound ala and free gly is lower, whereas the level of free glu and ala, bound gly is higher than in mature animals. To the end of the 1st week, total amino acid content decreases, except GABA, which is increased. Aminon acid content begins to increase at the 21th and 28th days of postnatal life.     

Gfat1基因在2型糖尿病大鼠肺组织中的表达

观察2型糖尿病大鼠不同时期肺组织谷氨酰胺果糖转移酶1(Gfat1)的表达情况.方法 SD大鼠随机分为正常对照组和模型组,对照组18只,模型组28只.模型组高脂饲料喂养2个月后,腹腔注射链脲佐菌素(STZ 15mg/kg)复制糖尿病模型,统计体重变化及空腹血糖值.RT-PCR方法检测造模成功后2周、4周和6周肺组织Gfat1 mRNA表达.结果 模型组大鼠体重增长较快,造模开始第28天,第42天,第56天和第70天高脂模型组与对照组体重差异有显著性(P＜0.05).注射STZ的高脂模型组空腹血糖值较高(FBG≥10.0),和对照组比较,FBG差异有极显著性(P＜0.01).糖尿病大鼠造模成功后2周,模型组肺组织Gfat1的表达低于对照组,与对照组比较差异无显著性(P＞0.05),4周模型组Gfat1的表达高于对照组,模型组与对照组比较差异有显著性(P＜0.05).6周模型组Gfat1的表达高于对照组,但模型组与对照组比较差异无显著性(P＞0.05).结论 大鼠饲喂高脂饲料结合腹腔注射STZ可成功建立2型糖尿病大鼠模型;在不同时期2型糖尿病大鼠肺组织中,Gfat1表达水平发生改变.     

Transneuronal induction of adrenal ornithine decarboxylase through descending spinal pathways

Induction of adrenal ornithine decarboxylase (ODC) was studied in rats that had previously undergone hemisection of the spinal cord at the C5–C6 level. Control rats were sham-operated. In the latter, the stress of immobilization produced symmetrical increases in ODC of the adrenal medulla. In rats with cord hemisection a quantitatively similar increase was observed only on the intact side, the response of adrenomedullary ODC of the lesioned side being significantly smaller. Induction of adrenomedullary ODC in hemisected rats by administration of apomorphine or of 2-deoxyglucose resulted in the same pattern of response as after immobilization. Induction of adrenocortical ODC by immobilization or apomorphine was not affected by cord hemisection. The results demonstrate the existence of both ipsilateral and contralateral components of descending spinal pathways for the induction of adrenomedullary ODC, the ipsilateral fibres exerting a preponderant effect.     

The effect of chronic vs. acute injection of vasopressin on animal learning and memory

The effect of chronic and acute treatment with DDAVP, a vasopressin analog, was studied in 2 month old male rats, using an active avoidance test in a shuttle box. The experiment lasted 6 weeks: an acquisition period of 4 weeks and an extinction period of 2 weeks. Rats were treated one hour before behavioral testing 3 times a week for 6 weeks with either DDAVP 20 micrograms/rat/day for the whole period (chronic group) or with DDAVP for the first week and again once only on the first day of the extinction period (acute group) or with saline. Chronic treatment with DDAVP resulted in better acquisition and in a marked retardation of extinction compared with the acute treatment group. These results were obtained both in normal rats and in rats pretreated at age 5 days of life with intracisternal 6-OH dopamine.     

The neonatal glucocorticoid treatment-produced long-term changes of the pituitary-adrenal function and brain corticosteroid receptors in rats.

Two distinct periods of sensitivity to elevated glucocorticoid hormone levels during postnatal development of the pituitary-adrenal axis were studied. Wistar rats were injected subcutaneously (s.c.) with cortisol (1 mg/kg) on postnatal days 1-5 or 14-18. The steroid treatment during the first postnatal week resulted in a decrease of the morning basal and stress-induced plasma corticosterone levels in 30 day-old male rats, as well as in rats that were injected with cortisol on the third postnatal week. Stress-induced corticosterone levels in 90-day old cortisol-treated rats were determined in blood samples drawn from the tail vein before the restraint stress, immediately after the 20-min long stress, then 60 and 180 min afterwards. Only the rats treated with cortisol during the third week showed a prolonged stress-induced corticosterone secretion, with the highest corticosterone level in 180 min after the restraint stress. The early neonatal cortisol treatment had no effect on (3)H-corticosterone binding in all studied brain areas of the 90-day old rats. The rats treated with cortisol at the 14-17th postnatal days showed a significantly lower (3)H-corticosterone binding in the frontal cortex, hippocampus, and hypothalamus. These findings suggest that the third week of life in rats is more sensitive to elevated levels of corticosterone than the first one. The high level of glucocorticoids at this period has long-term effects on the efficiency of the negative feedback mechanisms provided by hypothalamus-pituitary-adrenal axis.     

运动训练和补肽抗大鼠骨骼肌衰老机制的初步研究

目的：观察6周负重训练和补充大豆多肽延缓I）_半乳糖大鼠骨骼肌衰老进程的作用效果,并探讨初步机制。方法：SD雄性大鼠3月龄60只,随机分为：6周安静组（C6）和6周模型组（M6）各6只,12周模型组（M12）、大负组（B12）、小负组（S12）、补肽组（P12）、补肽大负组（PB12）和补肽小负组（PS12）各8只,14月龄8只作为自然衰老组。分别于6周末和12周末处死大鼠,测试各项指标。结果：与C6相比,M6组大鼠各项指标出现不同程度的衰老表现;与M12组相比,负重或补肽可以显著提高各干预组大鼠骨骼肌超氧化物歧化酶（SOD）活力以及SOD/MDA,血清生长激素（GH）、胰岛素样生长因子I（IGF-I）含量和骨骼肌IGF-ImRNA表达量,降低骨骼肌丙二醛（MDA）含量,两种方式均具有明显的交互作用。结论：D-半乳糖6周皮下注射,能成功复制亚急性大鼠骨骼肌衰老模型,再经过6周负重训练或补肽均可以有效的缓解D-半乳糖大鼠骨骼肌的衰老进程,两者联合运用效果尤为明显。初步机制可能与减轻骨骼肌氧化应激以及脂质过氧化,纠正激素及相关因子的代谢紊乱,增加骨骼肌IGF-ImRNA的表达等有关。     

Two types of "spike-wave" discharges in the electrocorticogram of WAG/Rij rats, the genetic model of absence epilepsy

WAG/Rij rats were injected with apomorphine (0.5 mg/kg, i.p.), an agonist of D2 receptors. Two types of spike-wave discharges (generalized and local) were found in the baseline ECoG of the intact and injected rats. Injections of apomorphine led to a suppression of the generalized (type 1) for about 30 minutes and a 8-10-fold increase in the local spike-wave discharges (type 2) within 4-6 minutes. Since it has been shown earlier that haloperidol, which acts on dopamine receptors oppositely to apomorphine, enhance the generalized spike-wave activity and suppress the local discharges. Thus, the different pharmacological characteristics of the two types of spike-wave activity suggest the controlling role of the dopaminergic system in the processes of spike-wave generation.