恩卡胺大鼠体内药物动力学的实验研究

采用 HPLC 法测定大鼠血清中的恩卡胺浓度,研究了不同剂量恩卡胺一次灌胃后在大鼠体内的药物动力学。结果表明其符合一室模型,且口服吸收迅速,消除半衰期短,分布容积大。大剂量给药后达峰时间推迟,消除半衰期延长。     

白细胞介素-6在小鼠体内的药动学研究

本文应用生物活性测定法,在小鼠体内对白细胞介素-6静脉、腹腔给药,进行了药动学研究。结果表明:静脉给药后,白细胞介素-6在小鼠体内分布较快,T_(1╱2)α=1.5min,消除也较快,T_(1╱2)β=0.38h,体内停留时间较短,不适于临床治疗;腹腔给药后缓慢吸收,Tp=0.73h,Cp=5.9×10~(?)u/ml,分布及消除较静脉给药慢,T_(1╱2)α=0.67h,T_(1/2)β=0.67h;T_(1╱2)β=2.9h,给药后6h内,体内仍保留一定量的药物,适于临床治疗。     

卡铂腹腔给药体内分布实验

应用原子吸收光谱法在大鼠体内测定脏器组织中铂含量,了解卡铂腹腔给药的体内分布。结果表明,给药后14d内体内主要脏器均有铂存在,肾脏组织中含量最高。这提示,卡铂腹腔内化疗可防治消化道肿瘤的术后复发,同时应注意肾功能保护。     

LACK OF EFFECT OF BROMOCRIPTINE ON SERUM LEVELS OF CALCIUM IN THE RAT

1. The effect of bromocriptine (a prolactin suppressant drug) on the serum levels of calcium was studied in the male rat. The drug was administered subcutaneously at a dosage of 100μg per 100 g body weight three times per day. 2. Chronic treatment with bromocriptine had no significant effect on the serum calcium levels. It appears that neither bromocriptine per se nor normal circulating prolactin levels exert any significant influence on blood calcium homeostasis.     

HYPOTENSIVE ACTIVITY OF AQUEOUS EXTRACT OF ANDROGRAPHIS PANICULATA IN RATS

1. The hypotensive activity of an aqueous extract of Andrographis paniculata was studied using chronic intraperitoneal (i.p) infusions by osmotic pumps. The extract exhibited a dose-dependent hypotensive effect on the systolic blood presure (SBP) of spontaneously hypertensive rats (SHR). 2. The optimum hypotensive dose determined was repeated in a study in SHR and their normotensive controls, Wistar Kyoto (WKY) rats, to demonstrate its comparative effects on the SBP, plasma and lung angiotensin-converting enzyme (ACE) activities, as well as on lipid peroxidation in the kidneys, as measured by thiobarbituric acid (TBA) assay. 3. The extract significantly lowered the SBP of both SHR and WKY rats. 4. Plasma, but not lung, ACE activity and kidney TBA level were significantly lower in extract-treated SHR when compared with vehicle-treated SHR controls. 5. Plasma and lung ACE activities as well as kidney TBA levels were not significantly different between extract-and vehicle-treated WKY rats. 6. This study indicates that the aqueous extract of A. paniculata lowers SBP in the SHR possibly by reducing circulating ACE in the plasma as well as by reducing free radical levels in the kidneys. The mechanism(s) of hypotensive action seems to be different in WKY rats.     

DEVELOPMENT OF HYPERTENSION AND PROTEINURIA WITH AGE IN FAWN-HOODED RATS

Blood pressure and urinary protein excretion were monitored in male fawn hooded rats (FH rats) from 8 until 46 weeks of age. Mild hypertension was already observed at 8 weeks of age. Between the age of 5 and 7 months the blood pressure rose steeply to a plateau of about 200 mmHg. Then it stabilized and the level was different for animals of different litters but similar for littermates. Concomitantly with the increase in blood pressure, proteinuria increased with age. Examination of renal tissue at 6.5 and 9 months of age revealed the presence of focal and segmental glomerulosclerosis. The renal changes were not accompanied by gross alterations in renal function. In animals with severe hypertension pronounced proteinuria occurred, and they appeared to form a distinct class. In some of the animals intermittent haematuria occurred. Persistent haematuria, however, had a bad prognosis. There was no glucosuria. Water intake of the animals with severe hypertension was increased. Water intake of young FH rats was found to be of value for predicting the severity of the hypertension in these animals at a later age. It is concluded that the FH rat is an example of a non-inbred rat strain showing spontaneous hypertension. This hypertension may result from an aberrant renal water handling and/or volume regulation.     

牛磺酸对大鼠杏仁核点燃的作用

用大鼠杏仁核点燃模型（Ｋｉｎｄｌｉｎｇ ｍｏｄｅｌ）,研究牛磺酸对点燃发展进程及完全点燃的大鼠的作用。每日一次刺激大鼠右侧杏仁核（４０ｕＡ、６０ＨＺ、波宽１ｍｓ、矩形方波１秒）,在１３次产生点燃效应的Ｖ期反应,刺激后放电时间显著延长。脑室注射牛磺酸２００ｕｇ、４００ｕｇ可显著抑制眯燃效应的Ｖ期反应（Ｐ〈０．０１）,但对已点燃的大鼠无抑制作用。提示牛磺酸作为内源性的氨基酸神经递质,在预防癫痫的发展方     

INVOLVEMENT OF PROLYLCARBOXYPEPTIDASE IN THE EFFECT OF RUTAECARPINE ON THE REGRESSION OF MESENTERIC ARTERY HYPERTROPHY IN RENOVASCULAR HYPERTENSIVE RATS

• 1 Previous studies indicate that rutaecarpine blocks increases in blood pressure and inhibits vascular hypertrophy in experimentally hypertensive rats. The aim of the present study was to determine whether the effects of rutaecarpine are related to activation of prolylcarboxypeptidase (PRCP).
• 2 Renovascular hypertensive rats (Goldblatt two‐kidney, one‐clip (2K1C)) were developed using male Sprague‐Dawley rats. Chronic treatment with rutaecarpine (10 or 40 mg/kg per day) or losartan (20 mg/kg per day) for 4 weeks to the hypertensive rats caused a sustained dose‐dependent attenuation of increases in blood pressure, increased lumen diameter and decreased media thickness, which was accompanied by a similar reduction in the media cross‐sectional area : lumen area ratio in mesenteric arteries compared with untreated hypertensive rats.
• 3 Angiotensin (Ang) II expression was significantly increased in mesenteric arteries of hypertensive rats compared with sham‐operated rats. No significant differences in plasma AngII levels were observed between untreated hypertensive and sham‐operated rats. Hypertensive rats treated with high‐dose rutaecarpine had significantly decreased Ang II levels in both the plasma and mesenteric arteries.
• 4 Expression of PRCP protein or kallikrein mRNA was significantly inhibited in the right kidneys and mesenteric arteries of hypertensive rats. However, expression of PRCP protein and kallikrein mRNA was significantly increased after treatment with rutaecarpine or losartan (20 mg/kg per day).
• 5 The data suggest that the repression of increases in systolic blood pressure and reversal of mesenteric artery remodelling by rutaecarpine may be related to increased expression of PRCP in the circulation and small arteries in 2K1C hypertensive rats.

     

卡铂和顺铂在大鼠体内的药动学

应用石墨炉原子吸收法,对国产卡铂和顺铂在大鼠体内的药动学进行了比较。两药的药时过程均可按二室开放模型拟合。卡铂的 T_(1/2β)为14～16h,顺铂为23h。24h 内卡铂经尿排泄90%,顺铂约39%。10mg/kg 顺铂的组织分布及药时曲线下面积分别与60mg/kg 及与30mg/kg 卡铂相近。这些结果与卡铂的肾毒性明显小于顺铂相符合。     

建立大鼠甲基苯丙胺的神经精神毒性模型

目的:建立甲基苯丙胺(MA)慢性依赖大鼠模型及评价体系。方法:SD大鼠60只,随机分为6组:对照组、2 mg·kg-1MA组、10 mg·kg-1MA组、20 mg·kg-1MA组、30 mg·kg-1MA组、40 mg·kg-1MA组。观察记录实验大鼠给药后刻板行为变化,并检测记录大鼠的体重改变、条件性位置偏爱实验结果。建立MA依赖大鼠模型。结果:根据实验动物给药后行为、体重改变以及是否形成条件性位置偏爱3个方面的指标变化,建立MA依赖大鼠模型和评价指标体系。结论:成功建立了MA慢性依赖大鼠模型和评价指标体系。     

ADRENALINE SYNTHESIZING NERVE CELLS IN THE MEDULLA OF NORMOTENSIVE AND HYPERTENSIVE RATS

1. We have studied the number and distribution of adrenaline synthesizing nerve cells in the medulla oblongata of the rat, using a combination of immunofluorescence to visualize the enzyme phenylethanolamine-N-methyltransferase (PNMT) and catecholamine fluorescence to detect central catecholamines. 2. The distribution of adrenaline synthesizing nerve cells was similar in normo-tensive (Wistar Kyoto) rats, spontaneous hypertensive rats, and stroke-prone rats. Few of the cells visualized by PNMT immunofluorescence were detected by the Faglu fluorescence method for catecholamines. The CI (ventrolateral) and C2 (dorsomedial) groups of PNMT cells were anatomically distinct from the Al and A2 groups of catecholamine fluorescent cells and lay rostral to these cells within the medulla. There was a third group of adrenaline synthesizing cells close to the midline in the rostral medulla, and we have called this the C3 group. 3. There was a 32% increase in the number of PNMT cells in the medulla of 4-week-old stroke-prone rats. 4. PNMT enzyme activity in a cross-segment of the medulla containing the adrenaline synthesizing cells was also increased by 30% in both spontaneous hypertensive rats and stroke-prone rats.     

褐藻胶对大鼠实验性肝纤维化的防治作用

褐藻胶是海藻的提取物，本文研究了四氯化碳诱导的大鼠肝纤维化模用褐藻胶后肝脏组织学和血清ＰＣⅢ和ＨＡ水平变化。结果表明，褐藻胶对实验性肝纤维化有一定的防治作用。     

粉防己碱对大鼠吗啡戒断反应的影响

目的:研究钙拮抗剂粉防己碱 (Tet)对大鼠吗啡戒断反应的影响。方法··:以剂量递增法形成吗啡依赖模型 ,用纳洛酮催促戒断 ,戒断症状按柳田知司评分法给予评分。结果··:吗啡阳性组戒断症状分值为26.5±s7.1;Tet(30mg·kg-1) +吗啡组和Tet(60mg·kg-1) +吗啡组的戒断症状分值分别为 :11.7±s4.6、6.6±s4.3 ,与吗啡阳性组相比有极显著性差异 (P<0.001)。结论··:Tet能抑制吗啡大鼠依赖的戒断症状。     

MAINTENANCE OF PSEUDOPREGNANCY BY PROLACTIN IN INDOMETHACIN TREATED RATS

1. The effects of bromocriptine and indomethacin on prolactin-induced pseudopregnancy were studied in pituitary grafted rats. 2. Administration of bromocriptine (a prolactin suppressant drug) at a total dose of 3 mg/kg body weight, given in 3 divided doses on day 5 of pseudo-pregnancy, effectively terminated it within 3 days. However, injection of indomethacin (a prostaglandin inhibitor) at a total dose of 6 mg/kg body weight, given in 3 divided doses, on the same day of pseudopregnancy had no significant effect on its duration. 3. It appears unlikely that the luteotrophic effect of prolactin on the corpus luteum is mediated by the stimulation of prostaglandin synthesis.     

IMPORTANCE OF CENTRAL SEROTONIN NEURONS IN THE HYPOTENSIVE ACTION OF METHYLDOPA IN THE RAT

1. Normotensive (WKY) and stroke prone spontaneously hypertensive (SHR-SP) rats were given methyldopa (200 mg/kg i.p.) daily for five days and their brains were then sectioned and processed with the Faglu method for catecholamine fluorescence. 2. This treatment with methyldopa induced a green fluorescence not seen in control animals, in cells coinciding with the B1–B9 groups of serotonin neurons in the brainstem. 3. Pretreatment with the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT, i.c.v.), which is relatively specific for serotonin neurons, prevented the appearance of this green fluorescence in the serotonin cell groups of rats given methyldopa. 4. Pretreatment with 5,7-DHT, i.c.v. approximately halved the magnitude of the hypotensive response to a single dose of methyldopa (80 mg/kg i.p.). 5. We suggest that central serotonin nerves contribute to the hypotensive action of methyldopa. 6. It is our hypothesis that methyldopa is taken up by these serotonin cells and that the green fluorescence reflects the production of α-methyldopamine, as a result of decarboxylation by the ubiquitous enzyme, L-aromatic amino acid decarboxylase.     

PHARMACOKINETICS OF THE ENANTIOMERS OF VERAPAMIL AFTER INTRAVENOUS AND ORAL ADMINISTRATION OF RACEMIC VERAPAMIL IN A RAT MODEL

Verapamil is a chiral calcium channel blocking drug which is useful clinically as the racemate in treating hypertension and arrhythmia. The published pharmacokinetic data for verapamil enantiomers in the rat model are limited. Utilizing a stereospecific high-performance liquid chromatographic (HPLC) assay, the enantiomeric disposition of verapamil is reported after intravenous (1·0 mg kg⁻¹) and oral (10 mg kg⁻¹) administration of racemic verapamil to the rat model. After intravenous administration the systemic clearance of R-verapamil was significantly greater than that of S-verapamil; 34·9 ± 7 against 2·7 ± 3·7 mL min⁻¹ kg⁻¹ (mean ± SD), respectively. After oral administration, the clearance of R-verapamil was significantly greater than that of S-verapamil, 889 ± 294 against 351 ± 109 mL min⁻¹ kg⁻¹, respectively. The apparent oral bioavailability of S-verapamil was greater than that of R-verapamil, 0·074 ± 0·031 against 0·041 ± 0·011, respectively. These data suggest that the disposition of verapamil in the rat is stereoselective; verapamil undergoes extensive stereoselective first-pass clearance after oral administration and the direction of stereoselectivity in plasma is opposite to that observed in the human. © 1997 John Wiley & Sons, Ltd.     

EFFECT OF ENALAPRIL ON BODY SODIUM AND HANDLING OF A SODIUM CHLORIDE LOAD IN HYPERTENSIVE AND NORMOTENSIVE RATS

1. The effect of enalapril on handling of an Na load and on body Na during 96 h of zero Na intake was measured in hypertensive rats (GH and SHR) and their normotensive controls (N and WKY) by a whole body counting method. 2. Enalapril treatment led to a greater fall in body Na in the first 24 h after the Na load (as expected from the known effect of ACE inhibition on aldosterone production) and thus to a slightly faster excretion of an amount equivalent to the load. 3. Enalapril-treated rats were unable to maintain body Na on a zero Na intake. This was also expected from the known effect on aldosterone production, though other mechanisms are not excluded. The effect was more marked in the SHR and WKY than in GH and N but there was no significant difference in this effect between the hypertensives and their respective control strains.