环丙沙星阴道泡腾片的药效学研究

观察了环丙沙星阴道泡腾片对金黄色葡萄球菌、绿脓杆菌及淋球菌引起的家兔阴道感染的治疗作用.每日一次给药(4 mg/kg),可明显缩短细菌培养转阴时间,其疗效优于口服(20mg/kg)及静注(10mg/kg)给药,并能有效地治疗阴道充血、水肿、糜烂、分泌物增多等病变.     

诃子提取物的皮肤过敏性及阴道刺激性研究

目的 通过研究诃子提取物对豚鼠的毒性作用开发诃子提取物新的制剂.方法 ①主动皮肤过敏实验:豚鼠27只按体重随机分成3组,每组9只,即诃子提取物组(40 mg/0.5 ml/kg)、生理盐水空白对照组(生理盐水0.5 ml/只)与1% 2,4二硝基氯代苯阳性对照组,剂量为0.5 ml/只,豚鼠经皮肤多次给药致敏后,观察其过敏反应.②阴道刺激性试验:取豚鼠12只按体重随机分成2组,每组6只,即诃子提取物组(40 mg/kg)、和赋形剂对照组(生理盐水对照),经阴道给药,观察其全身状态有无异常及阴道组织有无红斑和水肿等.结果 豚鼠给药后未发生皮肤过敏反应;经阴道给药后阴道组织正常,无红斑和水肿出现,同时全身状态无明显变化.结论 诃子提取物对豚鼠皮肤无过敏反应,对豚鼠全身及阴道局部无不良毒性反应,可以进一步开发新的外用型制剂.     

银杏叶提取物促进微循环作用研究

目的探讨银杏叶提取物（YXY）对小鼠耳廓微循环的影响,为临床治疗微循环障碍性疾病提供实验依据.方法将52只ICR小鼠随机分为5组（对照组,阳性对照组,YXY 60 mg/kg组、30 mg/kg组、15 mg/kg组）,均静脉注射给药.在WX-6微循环显微测试仪上测定给药前及给药后5,15,30 min时小鼠耳廓毛细血管数、细静脉及细动脉管径、细动脉血流速度.结果与结论YXY在15～60 mg/kg剂量范围内静脉给药,能剂量依赖性地增加毛细血管数,扩张细静脉、细动脉管径,加快细动脉血流速度,显示有明显改善微循环的作用.     

替莫唑胺的小鼠急性毒性试验

目的观察替莫唑胺对小鼠的急性毒性。方法采用灌胃给药和腹腔注射给药两种途径进行试验,采用Bliss法计算半数致死量(LD50)。结果一次给药替莫唑胺可以对小鼠产生急性毒性,使小鼠陆续死亡,观察至给药后14d及以上仍有动物死亡。结论本品小鼠灌胃给药LD50为173.90mg/kg(95%的可信限为154.49～199.75mg/kg),腹腔注射给药LD50为164.53mg/kg(95%的可信限为144.36～187.49mg/kg)。     

高山红景天提取物的药理研究

红景天提取物皮下注射100mg/kg,一次给药或连续三天给药均有抗游泳疲劳作用,100mg/kg一次给药具有抗抓棒疲劳作用,100—200mg/kg 均无增强或拮抗戊巴比妥钠催眠作用,90mg/kg 无抗常压缺氧作用,45—200mg/kg一次或多次给药均无抗低压缺氧作用,10mg/kg 无抗肾上腺素高血糖作用。红景天浸膏灌胃给药1.25—10.0g/kg 一次给药,或5g/kg 连续六天给药均无抗抓棒疲劳作用。红景天提取物给小鼠灌胃给药 LD_(50)为45.01±7.37g/kg,给小鼠腹腔注射 LD_(50)为2.68±0.67g/kg。     

更年轻片对去势更年期模型大鼠FSH、LH、PRL、E_2的影响及对小鼠镇静作用的研究

目的:研究更年轻片对去势更年期模型大鼠促卵泡激素(FSH)、黄体生成素(LH)、泌乳素(PRL)、血清雌二醇(E2)的影响及对小鼠的镇静作用。方法:通过手术去除SD雌性大鼠双侧卵巢以复制大鼠去势更年期模型。实验分为正常(等容生理盐水)、模型(等容生理盐水)、倍美力结合雌激素(104.2mg/kg)与更年轻高、中、低剂量(1040、520、260mg/kg)组,灌胃给药,每天1次,连续30d。观察大鼠给药前后体质量变化,测定血清中FSH、LH、PRL、E2水平,计算子宫系数和阴道上皮细胞角化率。50只雌性小鼠随机均分为空白(等容生理盐水)、安定片(5mg/kg)与更年轻高、中、低剂量(2080、1040、520mg/kg)组,灌胃给药,每天1次,连续5d。于末次给药后1h测定5min内小鼠的活动次数和站立次数。50只雌性小鼠随机均分为空白(等容生理盐水)、安定片(5mg/kg)与更年轻高、中、低剂量(2080、1040、520mg/kg)组,灌胃给药,每天1次,连续6d。于末次给药后1h腹腔注射戊巴比妥钠(40mg/kg),记录各组小鼠的睡眠潜伏期和睡眠持续时间。结果:与模型组比较,更年轻高、中、低剂量组FSH、LH和PRL水平明显降低,E2水平明显升高;阴道上皮细胞角化率明显提高;子宫系数明显增加。与空白组比较,更年轻高、中、低剂量组小鼠的活动次数和站立次数显著减少(P<0.05);睡眠时间明显延长。结论:更年轻片对去势更年期模型大鼠有一定的疗效,对小鼠有一定的镇静催眠作用。     

黑木耳多糖和五味子醇提物对对乙酰氨基酚致小鼠急性肝损伤的保护作用

目的：研究黑木耳多糖和五味子醇提取物配伍使用对对乙酰氨基酚引起的小鼠急性肝损伤协同保护作用。方法：以对乙酰氨基酚200mg/kg腹腔注射给药造成小鼠急性肝损伤模型,通过测定小鼠血液中丙氨酸氨基转移酶（ALT）、门冬氨酸氨基转移酶（AST）、谷胱甘肽S-转移酶（GST）和肝脏组织还原性谷胱甘肽（GSH）及丙二醛（MDA）的含量来评价五味子醇提取物、黑木耳多糖及二者配伍后对小鼠肝损伤的保护作用。结果：五味子醇提取物（200mg/kg）和黑木耳多糖（250mg/kg）单独给药对肝脏的保护作用不显著。二者配伍给药（五味子醇提取物＋黑木耳多糖,100mg/kg＋125mg/kg,200mg/kg＋250mg/kg）可以显著改善ALT、AST、GST、GSH和MDA各项指标（P〈0.05或P〈0.01）。两药相互作用指数CDI均小于1.00。结论：五味子醇提取物与黑木耳多糖配伍使用可以保护对乙酰氨基酚引起的急性肝损伤,二者作用呈现协同效应。     

替硝唑洗液的抗厌氧菌活性及对人阴道滴虫的杀灭作用

目的:观察替硝唑洗液的抗厌氧菌活性及对人阴道滴虫的杀灭作用。方法:采用肉汤试管稀释法测定抗厌氧菌的MIC及MBC ;采用家兔阴道感染人阴道滴虫的模型,观察其抗阴道毛滴虫的作用。结果:替硝唑洗液对200株厌氧菌(除乳杆菌、直杆菌外)均有较好的抗菌活性,其MIC₅₀均在2mg/L以下,MIC₉₀ 略高(16mg/L) ,MBC约为MIC的4～16倍。替硝唑洗液阴道内直接给药和阴道内冲洗,5mg/kg以上对阴道毛滴虫具有明显的杀灭作用,20mg/kg达痊愈。结论:替硝唑洗液具有明显的抗厌氧菌活性,且对人阴道毛滴虫具有很好的杀灭作用,其杀灭滴虫的作用强度优于碧洁洗液     

替硝唑洗液的抗厌氧菌活性及对人阴道滴虫的杀灭作用

目的 :观察替硝唑洗液的抗厌氧菌活性及对人阴道滴虫的杀灭作用。方法 :采用肉汤试管稀释法测定抗厌氧菌的MIC及MBC ;采用家兔阴道感染人阴道滴虫的模型 ,观察其抗阴道毛滴虫的作用。结果 :替硝唑洗液对 2 0 0株厌氧菌 (除乳杆菌、直杆菌外 )均有较好的抗菌活性 ,其MIC50 均在 2mg/L以下 ,MIC90 略高 ( 1 6mg/L) ,MBC约为MIC的 4～ 1 6倍。替硝唑洗液阴道内直接给药和阴道内冲洗 ,5mg/kg以上对阴道毛滴虫具有明显的杀灭作用 ,2 0mg/kg达痊愈。结论 :替硝唑洗液具有明显的抗厌氧菌活性 ,且对人阴道毛滴虫具有很好的杀灭作用 ,其杀灭滴虫的作用强度优于碧洁洗液     

用蒙特卡罗模型探索头孢他美钠的给药方案

目的用蒙特卡罗模型,研究注射用头孢他美钠在犬体内的药效学与药动学的关系,探索合理的给药方案,为临床用药提供参考。方法 6只健康beagle犬(A、B组)交叉静脉注射190mg或264mg头孢他美钠,不同时间点取血,采用HPLC法测定血药浓度,用一室模型计算药动学参数,用蒙特卡罗模型预测头孢他美钠在四种不同给药方案下的治疗效果。结果 190mg组的犬主要药动学参数T1/2,CL,V为(1.21±0.24)h,(115.46±13.02)mL/h/kg,(202.50±50.91)mL/kg。264mg组的犬主要药动学参数T1/2,CL,V为(1.27±0.51)h,(105.75±11.22)mL/h/kg,(189.94±62.23)mL/kg,通过蒙特卡罗模拟,得到头孢他美钠在不同给药方案下的PK-PD曲线及敏感性折点。结论敏感菌感染并以%T>MIC90≥50%为治疗目标时建议选择333mg静脉注射,每8h给药一次(q8h,下同)或500mg,3h静脉滴注,q12h;以%T>MIC90≥65%为治疗目标时建议选择333mg,3h静脉滴注,q8h;耐药菌感染则需要加大剂量或重新选择新的给药方案。     

In vivo antitumor effects of bitter principles from the antlered form of fruiting bodies of Ganoderma lucidum

Two triterpene fractions and a single ganoderma alcohol obtained from an antlered form of the fruiting bodies of Ganoderma lucidum were examined for their antitumor effects on the growth of inoculated mouse Lewis lung carcinoma in mice by intraperitoneal administration. The ganoderma alcohol fraction significantly suppressed the tumor growth at doses of 50 and 100 mg/kg in the treatment period, and even after the administration, showing antitumor activity with a T/C value of 70.6% at a dose of 100 mg/kg. On the other hand, no obvious activity was shown at each dose in the ganoderma-acid-fraction-treated groups. Furthermore, ganoderiol F, which exhibited the strongest cytotoxicity against four tumor cell lines among five ganoderma alcohols examined, remarkably inhibited the tumor growth, accounting for 63.7% and 78.7% of control group at a dose of 5 mg/kg, 54.1% and 63.0% at a dose of 10 mg/kg, and 47.7% and 53.9% at a dose of 20 mg/kg in and after the administration period, respectively, in a dose-dependent manner. These results suggest that the antitumor effects of bitter principles in G. lucidum are mainly due to ganoderma alcohols.     

刺五加注射液对化疗药物心脏损伤保护及辅助治疗的实验研究

目的 研究刺五加注射液对化疗药物阿霉素诱导心肌损伤的保护及助眠、抗抑郁作用,为其临床的辅助治疗应用提供实验依据。方法 1）大鼠ip 2.5 mg/kg的盐酸阿霉素,每周1次,连续6周,诱导大鼠心脏毒性模型;于阿霉素注射后立即尾静脉输注药液,时长1 h,共6次,对照组、模型组给予生理盐水,受试药组给予刺五加注射液（50、100、200 mg/kg,以总黄酮计）,阳性对照组给予参芪扶正注射液（25 mL/kg）;测定大鼠血清心肌酶、炎性因子,以及心肌组织病理改变。2）以地西泮（0.5 mg/kg）为阳性对照,测定刺五加注射液（30、60、120 mg/kg）对戊巴比妥钠阈剂量（45 mg/kg）及阈下剂量（30 mg/kg）致小鼠睡眠的影响。3）采用小鼠悬尾实验,以氟西汀（20 mg/kg）为阳性对照,测定刺五加注射液（30、60、120 mg/kg）对不动时间的影响,观察其抗抑郁作用。结果 与模型组比较,刺五加注射液50、100、200 mg/kg不同程度减轻心肌病理改变,减少心肌酶乳酸脱氢酶（LDH）、肌酸激酶同工酶MB（CK-MB）漏出,除刺五加注射液50 mg/kg组CK-MB外,均差异显著（P<0.05）;可使IL-1β、IL-6、TNF-α水平不同程度降低,其中100、200 mg/kg组均差异显著（P<0.05、0.01）。与对照组比较,刺五加注射液30、60、120 mg/kg剂量相关性地显著缩短小鼠睡眠潜伏期（P<0.05、0.01、0.001）,120 mg/kg组显著延长睡眠时间（P<0.001）,60、120 mg/kg组显著增加入睡率（P<0.05、0.01）。与对照组比较,刺五加注射液各剂量组明显缩短小鼠悬尾不动时间（P<0.05、0.01）。结论 刺五加注射液对化疗药物阿霉素导致的心肌损伤治疗效果明显,而且能助眠、抗抑郁,这些作用对于恢复机体体力、促进健康有重要作用。     

Effects of drugs on mushroom poisoning induced in the rat byCortinarius speciosissimus

Summary The effect of phenobarbital and phenylbutazone treatment on the renal damage induced by the toxic mushroomCortinarius speciosissimus was studied in female rats. Phenobarbital sodium was given in drinking water (0.05% solution) for 11 days prior to the administration of mushroom. Phenylbutazone was given s.c. in doses of 50 and 100 mg/kg 1 h before the mushroom administration. Homogenized mushroom was given orally by stomach tube at a dose of 250 mg dried mushroom/kg body weight.It was found that the phenobarbital treatment strongly increased the damage induced byC. speciosissimus in the tubules of the kidney cortex but had no effect on the inflammation in the renal outer medullary zone induced by this toxic mushroom. Phenylbutazone treatment had no effect on the renal damage induced byC. speciosissimus.     

Effects of morphine alone and in combination with naloxone or d-amphetamine on shock-maintained behavior in the squirrel monkey

Key-pressing behavior in the squirrel monkey was maintained under an 8-min fixed-interval (FI) schedule of electric-shock delivery. The acute i.m. administration of morphine prior to a daily session decreased response rates at doses of 1.0–3.0 mg/kg but had little systematic effect on rate at doses of 0.03–0.3 mg/kg. When naloxone was administered concomitantly with morphine prior to a session, 0.01 mg/kg naloxone required a three-fold increase in the dose of morphine necessary to obtain decreased response rates, 0.1 mg/kg naloxone required a 30-fold increase in morphine, and 1.0 mg/kg required more than a 30-fold increase in morphine. Moreover, the administration of naloxone with morphine resulted in increased rates of responding at certain combinations of doses of the two drugs. The administration of d-amphetamine (0.03 or 0.1 mg/kg) alone increased mean response rates under the FI schedule; when combined with 0.03–0.3 mg/kg morphine the increases in responding were greater than obtained with d-amphetamine alone. The negative slope of the linear regression lines relating the effects of morphine to control rates of responding engendered under the FI schedule was decreased when morphine was combined with naloxone, but not with d-amphetamine. These results show that naloxone, but not d-amphetamine, can antagonize the response-rate decreasing effect of morphine when responding in the squirrel monkey is maintained by response-produced electric shock.     

The inhibitory effects of garlic and <Emphasis Type="Italic">Panax ginseng</Emphasis> extract standardized with ginsenoside Rg3 on the genotoxicity,biochemical, and histological changes induced by ethylenediaminetetraacetic acid in male rats

Ethylenediaminetetraacetic acid (EDTA) is widely used in food and other industries to sequester metal ions and to prevent their disadvantageous effects. The objective of the current study was to evaluate the protective effect of Panax ginseng extract standardized with ginsenoside Rg3 (ginsenoside Rg3 content was 3.6% w/w, i.e., 36 μg/mg P. ginseng extract) and garlic against EDTA-induced biochemical, genotoxic, and histological changes in rats. Forty male rats were divided into eight treatment groups and treated for 7 days as follows: the control group, the group treated with EDTA (20 mg/kg b.w) and the groups treated with P. ginseng extract (20 mg/kg b.w), garlic (5 mg/kg b.w), P. ginseng plus garlic alone or in combination with EDTA. In vivo bone marrow micronucleus test and random amplified polymorphism DNA-PCR (RAPD-PCR) method were performed to assess the antigenotoxic effect of both protective agents. The results indicated that EDTA administration caused a significant decrease in the serum biochemical parameters and antioxidant enzymes activity. The administration also increased lipid peroxidation and the incidence of micronucleated polychromatic erythrocytes (MnPCEs), caused appearance of some changes in polymorphism band patterns, and induced different histopathological lesions in the livers, kidneys, and testis. Treatment with P. ginseng, garlic alone or plus EDTA significantly improved all the tested parameters. Moreover, P. ginseng extract was found to be more effective than garlic in restoring the parameters that were altered by EDTA.     

左卡尼汀通过增加UCP1和p-AKT的表达活化高脂血症大鼠棕色脂肪细胞的研究

目的探讨左卡尼汀对高脂喂养大鼠棕色脂肪的影响及其相关机制。方法将30只SD大鼠随机分为对照组、模型组和左卡尼汀低、中、高剂量(100、200、300mg/kg)组,每组各6只。每日ig给药,治疗12周后称重、处死大鼠,收集血清和棕色脂肪组织,检测血清相关生化指标,测定棕色脂肪组织中解偶联蛋白1(UCP1)和磷酸化AKT(p-AKT)的表达水平。结果与模型组相比,左卡尼汀100、200、300 mg/kg组的总胆固醇(TC)、三酰甘油(TG)明显降低,高密度脂蛋白胆固醇(HDL-C)明显升高(P0.05);左卡尼汀100、200 mg/kg组的体质量明显降低,棕色脂肪组织(BAT)质量、BAT质量/体质量明显升高(P0.05)。与模型组相比,左卡尼汀100、200mg/kg组BAT中UCP1RNA明显增加,差异有统计学意义(P0.05)。与模型组相比,左卡尼汀组100、200、300mg/kg组BAT中UCP1和p-AKT蛋白表达明显增加,差异有统计学意义(P0.05、0.01),且呈剂量相关性。结论左卡尼汀具有降脂和促进棕色脂肪活化的作用,这可能与其增加棕色脂肪组织中UCP1和p-AKT的表达有关。     

Studies on the mechanism of methyl-Dopa-induced mydriasis in the cat

Summary alpha-methyl-Dopa (10–100 mg/kg, i.v.) produced a dose-dependent mydriasis in cats anaesthetized with pentobarbital (30 mg/kg, i.p.). The onset was gradual, reaching a maximum plateau in 2–2.5 h. Intracerebroventricular administration of 1 or 3 mg of alpha-methyl Dopa (MD) also produced pupillary dilation with a similar time course. These dosages were without effect when given intravenously. Pretreatment with the alpha ₂-adrenoceptor antagonist, yohimbine (0.5 mg/kg, i.v.), blocked the pupillary response to MD. The alpha ₁-adrenoceptor antagonist, prazosin (1.0 mg/kg, i.p.), was ineffective. Selective enzymatic blockade with 3-hydroxy-benzyl-hydrazine (NSD-1015; 25 mg/kg, i.p.), a Dopa-decarboxylase enzyme inhibitor, as well as with bis (4-methyl-homopiperazinyl-thiocarbonyl) disulfide (FLA-63; 2.5 mg/kg, i.p.), a dopamine-beta-hydroxylase blocker, prevented the mydriatic effect of MD. These results support the hypothesis that MD produces a clonidine-like, CNS mediated mydriasis in the cat, primarily by action of its metabolite alpha-methyl-noradrenaline acting on alpha ₂-adrenoceptors.     

Interaction between d-amphetamine and ethanol with respect to locomotion,stereotypies, ethanol sleeping time,and the kinetics of drug elimination

The interaction between d-amphetamine and ethanol with respect to locomotor activity, stereotyped behavior, and sleeping time was investigated in rats. Ethanol 0.8 g/kg i.p. enhanced and prolonged locomotor activity produced by d-amphetamine 1 mg/kg s.c. The increased motility after 5 mg/kg d-amphetamine was not influenced by alcohol 0.8 g/kg i.p. or 3.2 g/kg orally, but slightly protracted. Stereotyped head and paw movements as well as stereotyped licking, were distinctly strengthened and protracted by 3.2 g/kg ethanol orally. The modified d-amphetamine motility and stereotypies can be explained by alcohol-induced prolongation of the life of d-amphetamine. The effect is produced by alcohol's inhibition d-amphetamine p-hydroxylation in rat liver. After 3.2 g/kg ethanol i.p., the sleeping time of male rats amounted to 153 min. Simultaneous administration of 5 mg/kg d-amphetamine s.c. reduced the sleeping time to 84 min. This is obviously based on a central antagonism.     

Altered sensitivity to d-methylamphetamine,apomorphine, and haloperidol in rhesus monkeys depleted of caudate dopamine by repeated administration of d-methylamphetamine

The long-term neurochemical and behavioral effects of repeated d-methylamphetamine (d-MA) administration were investigated using four male rhesus monkeys trained to lever-press for food on a DRL-40 s schedule of reinforcement. Dose-response curves for d-MA (0.0625–2.0 mg/kg), apomorphine (0.025–0.4 mg/kg), and haloperidol (0.005–0.04 mg/kg) on responding showed that repeated d-MA administration (0.5–16.0 mg/kg/day) decreased sensitivity to d-MA and to apomorphine but increased sensitivity to haloperidol. At 3–6 months after the last injection of d-MA, a 48.1% decrease in caudate dopamine (DA) was observed, with the frontal cortex, midbrain, and ponsmedulla showing no significant change. A trend toward increasing concentrations of norepinephrine was noted in the same brain areas, but only in the frontal cortex did this change reach significance. Specific binding of 3H-spiroperidol to caudate membrane preparations was not changed, while the V _max of the caudate DA re-uptake process declined 32%, with no change in K _m. These results suggest that exposure of DA neurons in the caudate nucleus to high concentrations of d-MA can lead to nerve terminal degeneration.     

Behavioural effects of amphetamine in a small primate: Relative potencies of the d- and l-isomers

Acute administration of d-amphetamine (up to 8 mg/kg) or l-amphetamine (up to 12 mg/kg) in the marmoset results in a dose-dependent increase in small head movements (checking), an almost total suppression of activities including eating, grooming, playing, and social interaction, but little change in the amount of movement. Severe stereotypy is seen at high doses of both isomers. The d-isomer has approximately twice the potency of the l-isomer in increasing checking behaviour.