正源方提取物对小鼠的抗疲劳、耐缺氧与镇痛作用

目的:研究正源方提取物对小鼠的抗疲劳、耐缺氧及镇痛作用。方法:实验分为正常对照(等容生理盐水)组、十全大补丸(1.75 g/kg)组与正源方提取物高、中、低剂量(12.00、6.00、3.00 g/kg)组,ig给药,每天1次,连续9 d。采用负重游泳实验和转棒实验,观察正源方提取物对小鼠的抗疲劳作用;采用常压耐缺氧法测定小鼠存活时间;采用光热辐射甩尾法测定小鼠的痛阈值。结果:与正常对照组比较,正源方提取物高、中剂量组小鼠力竭游泳时间、转棒时间延长;正源方提取物高、中、低剂量组小鼠存活时间延长,痛阈值增高,差异均有统计学意义(P<0.01或P<0.05)。结论:正源方提取物对小鼠具有明显的抗疲劳、耐缺氧与镇痛作用。     

细柱五加的药理作用研究

细柱五加(Acanthopanax gracilistylus W.W.Smith.)灌胃给药100g/kg(按生药量计算)可延长小鼠游泳时间,延长热应激小鼠存活时间。细柱五加灌胃给药100g/kg/日,连续4日,可抑制四氧嘧啶所致大鼠高血糖。细柱五加灌胃给药72g/kg和100g/kg均可减少水负荷小鼠尿量,均不延长低压缺氧小鼠存活时间。细柱五加灌胃给药50g/kg和100g/kg亦不延长常压缺氧小鼠存活时间。     

大株红景天胶囊常压耐缺氧和抗疲劳作用

目的探究大株红景天胶囊常压耐缺氧和抗疲劳作用。方法 BALB/c雄性小鼠按自主活动性随机分为空白对照组、复方丹参滴丸阳性对照组、红景天苷组、大株红景天胶囊低、中、高剂量组(0.35,0.7和1.4 g·kg~(-1)),每组10只。空白对照组给予生理盐水,各组连续灌胃给药7 d,每日1次。末次给药后,进行常压混合气体致缺氧实验(97%N2+3%O2)、密闭缺氧实验、负重游泳实验和转棒式疲劳仪实验,分别测定大株红景天胶囊对小鼠的耐缺氧和抗疲劳作用。结果常压混合气体缺氧实验表明,与对照组比较,大株红景天胶囊中、高剂量可显著延长小鼠存活时间(P<0.05)。密闭耐缺氧实验表明,与对照组比较,大株红景天胶囊各剂量组对小鼠密闭缺氧存活时间有延长趋势,但无统计学差异。负重游泳实验结果表明,与对照组比较,大株红景天胶囊中、高剂量组剂量依赖性显著延长小鼠游泳时间(P<0.01),且效果明显优于复方丹参滴丸(P<0.01)和红景天苷(P<0.01);转棒式疲劳仪实验结果表明,与对照组比较,大株红景天胶囊高剂量组可显著延长小鼠在棒时间(P<0.01),且效果明显优于红景天苷(P<0.01)。结论大株红景天胶囊可显著提高小鼠的耐缺氧和抗疲劳能力。     

吲哚拉新(Indolacin)的药理研究

吲哚拉新灌胃给药,对角叉菜胶所致大鼠踝关节肿胀具有抑制作用,其 ED_(50)为11.6±6.0mg/kg,对醋酸所致小鼠扭体反应具有抑制作用,其 ED_(50)为111.7±18.1mg/kg。吲哚拉新腹腔注射30mg/kg,对四联菌苗所致家兔体温升高具有降低作用。吲哚拉新灌胃给药80mg/kg 和100mg/kg,对部分大鼠有致胃溃疡作用;同时灌胃给予白芨—甘草和角叉菜胶,剂量均为1600mg/kg,均有抗吲哚拉新致胃溃疡作用。     

环丙氟哌酸的药效学和毒理学研究

本文研究了环丙氟哌酸的体外抗菌作用、体内保护作用、小鼠和大鼠一次给药的半数致死量和安全试验。结果表明,环丙氟哌酸对革兰氏阴性菌的MIC范围为0.005～0.19μg/ml,抗菌活性强于氟哌酸、氟啶酸和吡哌酸;对革兰氏阳性菌的 MIC为0.045～1.50μg/ml,其抗革兰氏阳性菌活性明显强于上述对照药。小鼠分别感染金葡球菌、大肠杆菌和绿脓杆菌后的半数有效量明显优于氟哌酸、氟啶酸和吡哌酸。小鼠一次给药的半数致死量,口服LD_(50)为2991.52mg/kg; 静脉为223.88mg/kg;肌肉和皮下的LD_(50)分别为831.08mg/kg和1133.42mg/kg. 大鼠口服LD_(50)>5000mg/kg,静脉LD_(50)>200mg/kg;肌肉和皮下分别为>1000mg/kg和>1200mg/kg。狗口服50mg/kg日服三次为期2日和口服100mg/kg日服一次为期7日,未见毒性反应和功能改变,也未见病理组织学变化。     

苦苣提取物的心血管保护作用研究

目的：观察苦苣提取物的心血管保护作用。方法：采用常压耐缺氧、饥饿小鼠生存时间、急性心肌缺血模型、电刺激诱发血栓形成模型等实验方法，观察苦苣提取物的心血管药理活性。结果：苦苣提取物灌胃给药12．5g/kg和6．3g／kg均能明显增加小鼠常压下耐缺氧存活时间，能够延长饥饿小鼠的生存时间。3、2g/kg可明显降低大鼠血液黏度，延长大鼠体内血栓形成时间。苦苣提取物3．2g/kg和1．6g／kg对由垂体后叶素所致冠状动脉痉挛引起的大鼠急性心肌缺血具有明显的拮抗作用。结论：苦苣提取物具有活血化淤、抗心肌缺血的心血管保护作用。     

人参根多糖对环磷酰胺抑制免疫功能的影响

人参根多糖灌胃给药100—200mg/kg,对环磷酰胺所致小鼠巨噬细胞吞噬功能抑制、溶血素形成抑制和迟发型超敏反应抑制均有恢复正常作用。     

当归(Angelica sinesis)及其成分阿魏酸钠对小鼠吞噬功能的影响

当归为中医常用的补血活血药之一。设想当归的补血活血可能和增强机体免疫功能有关,故进行本项研究。实验分两部分:(1)给小鼠静脉注射当归16g/kg或阿魏酸钠100～200mg/kg均能显著地促进单核吞噬细胞系统对刚果红的廓清率。(2)给小鼠灌胃阿魏酸钠0.3g/kg或皮下给0.2g/kg能增强腹腔巨噬细胞吞噬鸡红细胞的能力。皮下给当归20g/kg也有增强作用。     

红景天纳米粉对小鼠抗缺氧和抗疲劳作用的实验研究

目的探讨红景天纳米粉及普通粉的抗缺氧和抗疲劳作用,比较两者在使用量和作用强度上的差别。方法采用小鼠常压缺氧和常温游泳实验模型,分别灌胃给予不同剂量的红景天钠米粉和普通粉,连续5d,末次给药1h后测定小鼠的存活时间,同时对红景天纳米粉与普通粉小鼠存活时间和使用量方面进行药效学比较。结果红景天纳米粉具有明显的抗缺氧和抗疲劳作用,其中纳米粉0.5和0.25g.kg-1比普通粉1.5和1.0g.kg-1有更好的抗缺氧和抗疲劳作用。结论红景天经纳米化后,具有明显的抗缺氧和抗疲劳作用,同时显示小剂量的红景天纳米粉可达到大剂量普通粉的药效。     

当归(Angelica sinesis)及其成分阿魏酸钠对小鼠吞噬功能的影响

当归为中医常用的补血活血药之一。设想当归的补血活血可能和增强机体免疫功能有关,故进行本项研究。实验分两部分:(1)给小鼠静脉注射当归16g/kg或阿魏酸钠100～200mg/kg均能显著地促进单核吞噬细胞系统对刚果红的廓清率。(2)给小鼠灌胃阿魏酸钠0.3g/kg或皮下给0.2g/kg能增强腹腔巨噬细胞吞噬鸡红细胞的能力。皮下给当归20g/kg也有增强作用。     

关于抗肿瘤药物的研究 Ⅷ.N-甲酰溶肉瘤素酰苯丙氨酸乙酯(FSPA)对动物肿瘤的影响

N-甲酰溶肉瘤素酰苯丙氨酸乙酯(FSPA)对动物肿瘤影响的实驗,得到如下的結果:FSPA 100—200毫克/公斤/日能显著的抑制大自鼠吉田腹水肉瘤的生长.FSPA一次腹腔注射,观察二天的LD₅₀为4.5克/公斤.FSPA 100毫克/公斤/日連續14天对猴无明显毒性;200毫克/公斤/日,則对末稍血液中的白血細胞有抑制作用.     

Encephalopathy in rats and nephropathy in rats and mice after subchronic oral exposure to benzaldehyde

Male and female Fischer 344 rats and B6C3F1 mice were treated daily (5 days/wk) with benzaldehyde by gavage either in 12 doses of 0 (vehicle control), 100 (rats only), 200, 400, 800, 1600 or (for mice only) 3200 mg/kg body weight/day (followed by 2 days' observation without treatment), or for 90 days in doses of 0, 50, 100, 200, 400 or 800 mg/kg/day (rats) or 0, 75, 150, 300, 600 or 1200 mg/kg/day (mice). In the acute studies, benzaldehyde induced deaths and decreased body-weight gain in both sexes of rats given 800 or 1600 mg/kg/day and caused deaths in both sexes of mice given 1600 or 3200 mg/kg/day. In the 90-day studies, deaths occurred in both sexes of rats on 800 mg/kg/day and in male mice on 1200 mg/kg/day. Body-weight gain was depressed in male rats on 800 mg/kg/day, in male mice on 600 mg/kg/day and in female mice on 1200 mg/kg/day. Necrotic and degenerative lesions were seen in the cerebellar and hippocampal regions of the brain in both sexes of rats given 800 mg/kg/day, but not in mice. Renal tubular necrosis occurred in male and female rats on 800 mg/kg/day and in male mice on 1200 mg/kg/day. Mild epithelial hyperplasia or hyperkeratosis of the forestomach was seen in male and female rats on 800 mg/kg/day. In this limited study, the no-observed-toxic-effect doses of benzaldehyde administered by gavage were 400 mg/kg/day in male and female rats, 300 mg/kg/day in male mice and 600-1200 mg/kg/day in female mice.     

Preclinical toxicology studies with tobramycin

Tobramycin, an aminoglycoside antibiotic, has been administered to mice, rats, cats and dogs for toxicologic evaluation. The sc LD50 values in mice and rats were 441 and 969 mg/kg, respectively. Deaths were preceded by CNS depression and occurred within 1 hr of treatment. A 100 mg/kg iv dose in chloralose-anesthetized cats produced a moderate, transient decrease in blood pressure and a significant decrease in inspiratory volume and soleus twitch force. Rats were given daily sc doses of 15–120 mg/kg for 3 months. Renal tissue change, the only drug effect evident histologically, ranged in degree from a slight reparative nephrosis at the lowest dose to cortical tubular necrosis in some rats that received the highest dose. In a 1-month study, a daily im dose of 7.5 mg/kg had no apparent effect on dogs, but a 30 mg/kg dose produced severe renal damage. Vestibular injury occurred within less than 30 days in all cats that received daily sc doses of 50 mg/kg, but no vestibular changes were observed in cats that were given 65 doses of 25 mg/kg. The toxicologic effects observed in tobramycin-treated animals were qualitatively and quantitatively similar to those observed with gentamicin.     

No toxicological effects on acute and repeated oral gavage doses of single-wall or multi-wall carbon nanotube in rats

Three female Crl:CD(SD) rats/group were dosed with single wall carbon nanotube (SWCNT) or multi wall carbon nanotube (MWCNT) four times by gavage at a total of 50 mg/kg bw or 200 mg/kg bw (four equally divided doses at one-hour intervals). Acute oral doses of SWCNT and MWCNT caused neither death nor toxicological effects, and thus the oral LD50 values for SWCNT and MWCNT were considered to be greater than 50 mg/kg bw and 200 mg/kg bw, in rats respectively. Five or ten Crl:CD(SD) rats/sex were dosed with SWCNT once daily by gavage at a dose of 0 (control), 0.125, 1.25 or 12.5 mg/kg bw/day for 28 days with a 14-day recovery period (0 and 12.5 mg/kg bw/day groups). Six or twelve Crl:CD(SD) rats/sex were dosed with MWCNT once daily by gavage at a dose of 0 (control), 0.5, 5.0 or 50 mg/kg bw/day for 28 days with a 14-day recovery period (0 and 50 mg/kg bw/day groups). Based on no toxicological effects, the no observed adverse effect levels (NOAELs) of repeated dose toxicity of SWCNT and MWCNT were considered to be 12.5 mg/kg bw/day and 50 mg/kg bw/day (the highest dose tested), respectively. It was suggested that SWCNT and MWCNT dosed by gavage reached the gastro-intestinal tract as agglomerates and were mostly excreted via feces.     

Teratogenicity of oral diazepam and diphenylhydantoin in mice

Diazepam (DAP) and diphenylhydantoin (DPH) have anticonvulsant activity and structural similarities. Diphenylhydantoin is teratogenic in the mouse. The effects upon the offspring of mice treated orally with DAP or DPH during pregnancy were studied. DPH, 45, 87.5, or 125 mg/kg, and equimolar doses of DAP, 50, 100, or 140 mg/kg and DAP, 500 mg/kg, were administered orally once daily for 3 days on gestation days 8–10 or days 11–13; or for 1 day only between days 8 and 15 (vaginal plug = day 1). Diazepam, 280 or 400 mg/kg, were administered once only between days 11 and 14. All drugs were suspended in sodium carboxymethylcellulose (CMC 0.5%). The animals were sacrificed on day 19 and the fetuses were weighed and examined. Significant (p ≤0.05) increases of cleft palates over CMC controls were found in offspring following 3-day maternal administration of DAP, 140 mg/kg and DPH, 87.5 or 125 mg/kg on days 11 to 13; and single-day administration of DAP 400 mg/kg on days 11 to 14; and of DAP, 500 mg/kg and DPH, 125 mg/kg on days 11 to 15. There was a greater incidence of significant increases of resorptions and significantly depressed fetal body weights following single-day administration of DAP, 500 mg/kg than after all other treatments. In conclusion, oral DPH and oral DAP, at a higher dosage level, produce a similar teratogenic effect, cleft palate, in the Swiss-Webster mouse.     

Role of gastric acid and bile acids in the pathogenesis of compound 48/80-induced gastric lesions in rats

We studied the effects of various agents, which influence gastric acidity and bile acids, on compound 48/80 (48/80)-induced gastric lesions in rats. 48/80-Induced gastric lesions were produced by repeated intraperitoneal administration of 48/80 at 0.75 mg/kg once daily for 4 days. Test agents were given orally twice daily (30 min before and 9 hr after 48/80 administration) for 4 days. AI(OH)3 and sucralfate at 2000 mg/kg/day, a weak antacid dose, significantly inhibited (about 50-60%) the development of 48/80-induced lesions. Propantheline at 60 mg/kg/day and omeprazole at 60 or 200 mg/kg/day, which reduced gastric secretion for more than 12 hr, also significantly inhibited (about 30-40%) these lesions. Cimetidine at 200 mg/kg/day, which reduced gastric secretion for only 5 hr, had little effect on the lesion formation. Cholestyramine, which is a potent bile acids binding agent, had no effect on 48/80-induced lesions in doses of 600 or 2000 mg/kg/day. These results suggest that gastric acid, but not bile acids, is partly involved in the pathogenesis of 48/80-induced gastric lesions.     

Prenatal cocaine exposure in the laboratory mouse: effects on maternal water consumption and offspring outcome.

Pregnant mice were given 50 mg/kg cocaine HCl (1% solution, sc) once daily from gestation days 7 through 18 (sperm positive = day 0; term = day 19). Pair-fed and untreated control groups were also used. The pregnant cocaine-treated females showed normal weight gain and food consumption but had significantly increased water consumption. The cocaine-treated group had a significant increase in embryonic resorptions but no significant effects on stillbirths or postnatal mortality. The offspring of cocaine-treated females had significantly reduced birth weights and postnatal weight gains up to the age of 28 days. There was also a delay in their ear opening but not in other maturational milestones. Increased water consumption following cocaine treatment has been reported by other studies. We speculate that cocaine has a diuretic effect. We discuss the implications of this effect during pregnancy.     

二苯乙烯(芪)的一些药理作用

芪(二苯乙烯)通常用于化学工业,对其药理活性的研究很少。通过动物实验我们发现芪能明显保护CCl₄引起的小鼠肝损害,表现在使高的SGPT及SGOT降低、BSP潴留减少、肝组织病变减轻等。芪明显促进肝糖元生成,此作用强度与可的松相近,但芪没有可的松那样的抗炎作用。在去肾上腺小鼠,芪仍能明显促进肝糖元生成,故此作用似乎不通过体内的垂体-肾上腺系统。芪对小鼠戊巴比妥睡眠时间影响不明显。根据实验资料分析,芪对CCl₄肝损害的保护机制大概不是通过酶诱导,也不象某些抗氧化剂那样直接对抗CCl₄的作用,但有可能与其促进肝糖元生成有某种关系。芪有微弱的雌激素作用(约为己烯雌酚的数万分之一)。芪的毒性很低,小鼠一次腹腔注射LD₅₀为6.5 g/kg,灌胃LD₅₀大于8 g/kg,但油溶液毒性较大(灌胃LD₅₀为0.92g/kg)。长期大量给予芪,对雄小鼠的生长及睾丸发育有抑制作用,给狗服芪50 mg/kg/天连续一个月以上未见明显异常反应。     

硝唑咪衍生物S72014实验治疗动物血吸虫病的疗效与毒性的研究

口服硝唑咪衍生物S 72014对小鼠血吸虫病的化疗指数为21.2,较硝唑咪的5.8为大。病兔用S 72014 50～200mg/kg/天的2～14天疗法治疗时,减虫率均在90%以上。感染犬与猴每天用S 72014,125～210 mg/kg治疗,3次分服,疗程为7～14天时,均获得治愈。S 72014对小鼠的毒性较硝唑咪的低9倍以上。S 72014对小鼠和犬的中枢神经系统的作用较硝唑咪的为轻。在所用的剂量下,S 72014对犬与猴的肝、肾功能无明显影响,对心电图则引起暂时性的S-T段压低和T波平坦。较大剂量的S 72014对犬与猴的中枢神经系统、肝及肾有暂时性的病理损害,且明显抑制雄性动物的生精过程。S 72014与硝唑咪对犬可引起严重的再生障碍性贫血,但对猴的造血功能则无影响。