Kanglemycin C vs ciclosporin on immunosuppression in mice

目的：与环孢素（Ｃｉｃ）比较,研究康乐霉素Ｃ（Ｋａｎ）对小鼠免疫系统的影响．方法：皮肤迟发性超敏反应（ＤＨ）和环磷酰胺（Ｃｙｃ）增强型ＤＨ;同种异型皮肤和心脏移植;脾细胞溶血素测定;腹腔巨噬细胞吞噬中性红．结果：Ｋａｎ（１２５,２５,５０ｍｇ·ｋｇ－１·ｄ－１,ｉｇ,８ｄ）与Ｃｉｃ相似,抑制小鼠皮肤ＤＨ和Ｃｙｃ增强型ＤＨ（Ｐ＜００１）;延长小鼠同种异型皮肤和心脏移植物存活时间（Ｐ＜００１）;对溶血素产生也有抑制作用（Ｐ＜００１）;Ｋａｎ５０ｍｇ·ｋｇ－１·ｄ－１,ｉｇ,５ｄ与Ｃｙｃ相似,对小鼠腹腔巨噬细胞吞噬中性红无明显作用（Ｐ＞００５）．结论：Ｋａｎ显著抑制小鼠细胞免疫和体液免疫,但不影响巨噬细胞的吞噬．     

脂必妥对大鼠高脂血症模型血脂水平的影响

目的：研究脂必妥的降脂疗效。方法：通过对大鼠腹腔注射脂酶抑制剂——１０％泰洛沙泊溶液（３ｍＬ／ｋｇ）后７ｍｉｎ，分别用脂必妥２．５９，１．２９，０．６５ｇ／ｋｇ，及洛伐他汀１０ｍｇ／ｋｇ灌胃给药。结果：脂必妥２．５９ｇ／ｋｇ组及洛伐他汀组（１０ｍｇ／ｋｇ）的胆固醇（ＴＣ）值分别降低３３％（Ｐ＜０．０１）及３１％（Ｐ＜０．０１），组间比较Ｐ＞０．０５；低密度脂蛋白胆固醇（ＬＤＬ－ｃｈ）值分别降低５０％（Ｐ＜０．０１）及４４％（Ｐ＜０．０１）；脂必妥１．２９ｇ／ｋｇ组亦能降低ＴＣ及ＬＤＬ－ｃｈ值１８％（Ｐ＜０．０５）及２６％（Ｐ＜０．０５）；小剂量０．６５ｇ／ｋｇ的脂必妥仅能降低ＴＣ１４％（Ｐ＜０．０５）；各组对三酰甘油（ＴＧ）值均无显著降低作用（Ｐ＞０．０５）。结论：脂必妥有显著降低血脂过多大鼠ＴＣ及ＬＤＬ－ｃｈ值的作用。     

达曲班对脑缺血的保护作用

结扎大鼠左侧颈总、颈外动脉，由颈内动脉注射花生四烯酸致脑缺血。达曲班（１）（３．５、４．４ｍｇ·ｋｇ－１，ｉｖ）可使大鼠脑组织乳酸和丙二醛含量均较溶剂对照组明显降低（Ｐ＜０．０１），１（４．４ｍｇ·ｋｇ－１，ｉｖ）使超氧化物歧化酶（ＳＯＤ）活性明显升高（Ｐ＜０．０５），１（３．５、４．４ｍｇ·ｋｇ－１）使脑电图（ＥＥＧ）较溶剂对照组有所改善。小鼠腹腔注射１（５、１０ｍｇ·ｋｇ－１）可使其断头后头部喘息时间明显延长（Ｐ＜０．０１）。小鼠尾静脉注射ＫＣＮ（２．７５ｍｇ·ｋｇ－１）致组织中毒性缺氧，１（４ｍｇ·ｋｇ－１，ｉｐ）可明显提高其存活率（Ｐ＜０．０５），并求得１对抗组织中毒性缺氧的ＥＤ５０为４．４５ｍｇ·ｋｇ－１。上述结果提示１对大、小鼠脑缺血缺氧均有明显的保护作用     

对平骨散镇痛、抗炎作用的药理研究

平骨散０．７７或２．４ｇ／ｋｇｐｏ能显著抑制小鼠醋酸扭体反应及提高热板法的痛阈值（Ｐ＜０．０１），且能抑制二甲苯性耳壳肿胀度（Ｐ＜０．０１）；平骨散０．５４或１．６４９／ｋｇｐｏ对大鼠角叉菜胶性足肿胀率亦有抑制作用（Ｐ＜０．０５）。实验研究表明：平骨散具有镇痛、抗炎作用，与临床疗效相符。     

3,4‘,5—三羟基芪—3—β—单—D—葡萄糖苷减轻动脉内皮损伤性血栓形…

３，４＇，５－三羟基芪－３－β－单－Ｄ－葡萄糖苷对兔颈动脉内皮损伤性血栓形成的影响，方法：采用胰蛋白酶损伤兔颈动脉内皮诱导血栓形成模型。结果：Ｐｏｌｉｖ５或１０ｍｇ．ｋｇ＾－１均可显著减少血栓湿重（＜０．０５，＜０．０１）并抑制血小板聚集（Ｐ＜０．０５，Ｐ＜０．０１）并抑制血小板聚集（Ｐ，０．０５，Ｐ＜０．０１）．Ｐｏｌ０．３０－１．１５ｍｍｏｌ．Ｌ＾－１抑制血小板ＴＸＡ２生成（Ｐ＜０．０５，Ｐ＜     

米非司酮,环氧司坦及其合并用药的抗生育作用

大鼠妊娠ｄ１０，ＲＵ－４８６单用及与Ｅｐｏ１２ｍｇ·ｋｇ＾－１合用的ｉｇ抗生育ＤＥ５０（９５％可信限）分别为７．８（５．３－１０．０）及２．６（２．０－３．３）ｍｇ·ｋｇ＾－１（Ｐ〈０．０５）；Ｅｐｏ单用及与ＲＵ－４８６ ４ ｍｇ·ｋｇ＾－１合用的ｉｇ抗生育ＥＤ５０（９５％可信限）分别为２５．５（１９．４－３３．６）及５．１（４．７－７．４）ｍｇ·ｋｇ＾－１（Ｐ〈０．０５）。Ｅｐｏ１２ｍｇ·ｋｇ＾…     

肝胆结石片对动物胆红素结石的防石作用研究

研究结果表明：连续ｉｇ肝胆结石片１．５ｇ、３．０ｇ（生药）／（ｋｇ·ｄ）９８天，可使豚鼠的成石率由８８．９％分别降至３３．３％、１１．１％（ｐ均＜０．０１），有显著的防石作用。能抑制成石豚鼠血清、胆汁中游离胆红素、降低有或无石囊壁重，且能促进大鼠的胆汁分泌量增加（ｐ＜０．０５或０．０１）；有良好的利胆作用。对正常小鼠血清甘胆酸影响不明显，无明显急性毒性反应。     

红毛五加对免疫低下小鼠的影响

要环磷酰胺（ＣＹ）４０ｍｇ／ｋｇ造成小鼠免疫功能低下的实验证明：ｉｇ红毛五加水提取物６．０，３．０，１．５ｇ／（ｋｇ·ｄ）均能增加脾脏器官重量（ｒ＜０．０１）；在血清凝集素和给药量之间存在量效关系。本文还报道了外周Ｔ淋巴细胞阳性百分率动态变化特征。     

健脑降脂丸对小鼠空间分辨学习和记忆的影响

采用Ｙ型迷宫法证明，健脑降脂丸于实验前５日连续灌胃５．４ｇ／ｋｇ，２．７ｇ／ｋｇ，每日１次，均能提高小鼠学习记忆能力（Ｐ＜０．０１），且能巩固小鼠记忆成绩（Ｐ＜０．０５），其一次训练即达到学习指标的小鼠数比对照组高７０％．对小鼠学习记忆的作用与脑复康作用基本相同．健脑降脂丸对东莨菪碱所致学习障碍与脑复康有同样的保护作用     

海洋生物酸性多糖的抗银屑病作用及对免疫功能的影响

利用鼠阴道上皮模型及鼠尾鳞片表皮模型研究了酸性多糖类海洋药物ＨＡＩ－０９１３抗银屑病的作用，并进一步研究了对机体细胞免疫功能的影响。结果表明，ＨＡＩ－０９１３２５、５０、１００ｍｇ·ｋｇ－１可明显抑制雌激素期小鼠和大鼠阴道上皮细胞有丝分裂指数（Ｐ＜０．０１），显著提高小鼠尾鳞片颗粒层形成数（Ｐ＜０．０５），与阳性对照药氨甲喋呤（１ｍｇ·ｋｇ－１，ｉｐ）比较均无显著性差异。ＨＡＩ－０９１３２５、５０、１００ｍｇ·ｋｇ－１还可显著提高小鼠脾脏Ｔ淋巴细胞增殖活性（Ｐ＜０．０１）。结果提示ＨＡＩ－０９１３可能具有抑制银屑病患者表皮细胞增生，提高颗粒层形成及改善患者免疫功能低下状态的作用。     

Action of anti-tussive drugs on the emetic reflex of Suncus murinus (house musk shrew)

The cough and emetic reflexes involve a synchronized firing of motor neurones involved in respiratory control. Tachykinin NK1 receptor antagonists and 5-HT1A receptor agonists are examples of centrally acting drugs that reduce cough and emesis. In the present studies, therefore, we examined the possibility that other classes of drugs known to reducing cough have anti-emetic properties to prevent emesis induced by diverse challenges. We examined the potential of codeine (1-10 mg/kg), baclofen (1-10 mg/kg), scopolamine (0.3-10 mg/kg), diphenhydramine (1-10 mg/kg), imperialine (1-30 mg/kg) and verticine (0.3-3 mg/kg) to inhibit emesis induced by nicotine (5 mg/kg, s.c.), copper sulphate (120 mg/kg, intragastric), and provocative motion (4 cm horizontal displacement, delivered at 1 Hz) in Suncus murinus (house musk shrew). Only codeine had broad inhibitory properties (P<0.05) to antagonize emesis induced by all challenges with ID50 values ranging from 1.2 to 2.3 mg/kg. Baclofen antagonized emesis induced by nicotine (maximum reduction was 44.9%, P<0.05) and motion (maximum reduction was 97.3%, P<0.01), but potentiated copper sulphate-induced emesis (maximum potentiation was 73.0%, P<0.05). Scopolamine antagonized copper sulphate-induced emesis (maximum reduction was 61.2%, P<0.05) and imperialine antagonized nicotine-induced emesis (maximum reduction was 30.2%, P<0.01), but verticine potentiated motion-induced emesis (maximum potentiation was 60.0%, P<0.05). Diphenhydramine did not significantly reduce emesis induced by any of the challenges (P>0.05). In conclusion, codeine has broad inhibitory anti-emetic actions but a known ability to reduce coughing does not necessarily predict broad inhibitory anti-emetic properties.     

Effects of 6-[p-(4-phenylacetylpiperazin-1-yl)phenyl]-4,5-dihydro-3(2H)pyridazinone (CCI 17810) and aspirin on platelet aggregation and adhesiveness.

1. The effects of 6-[p-(4-phenylacetylpiperazin-1-yl)]-4,5-dihydro-3(2H)pyridazinon (CCI 17810) on platelet aggregation and adhesiveness have been investigated and compared with those of aspirin. 2. In vitro, CCI 17810 was a potent inhibitor of the aggregation of human platelets induced by collagen, adenosine 5'-diphosphate (ADP) (primary response), thrombin and arachidonic acid, with EC50 values in the range 0.5 to 10 micrograms/ml. The second phase of the response to adrenaline was blocked by concentrations in the range 15 to 25 micrograms/mg. Platelets from rats, rabbits and dogs were as sensitive as human platelets to the effects of CCI 17810. Aspirin was nearly as effective as CCI 17810 against collagen, and adrenaline but about 10 times less active against arachidonic acid; it did not inhibit the primary response to ADP and was only a weak inhibitor of thrombin-induced aggregation. 3. In mice, single oral doses of CCI 17810 in the range 12.5 to 100 mg/kg inhibited collagen-induced thrombocytopenia. Arachidonic acid-induced mortality was markedly reduced by 10 mg/kg and possibly slightly reduced by 1 mg/kg. Aspirin was considerably less active than CCI 17810 in inhibiting collagen-induced thrombocytopenia but was almost as active as CCI 17810 in reducing arachidonic acid-induced mortality. 4. In vitro, CCI 17810 reduced the adhesiveness of human platelets to glass beads (retention of platelets in glass bead columns). Single oral doses of CCI 17810 in the range 25 to 200 mg/kg reduced mouse platelet adhesiveness; rat platelet adhesiveness was reduced by doses in the range 12.5 to 100 mg/kg. Aspirin (20 or 200 mg/kg) slightly increased mouse platelet adhesiveness.     

阿司匹林抑制兔腹主动脉粥样斑块破裂及MMP-2表达的研究

目的研究阿司匹林稳定粥样斑块的作用及其可能的作用机制。方法采用♂新西兰兔高脂饮食加腹主动脉内膜剥脱术制成高脂性动脉粥样硬化模型,然后给予阿司匹林5~20mg·kg-1治疗4wk,实验末诱发斑块破裂,运用图像分析方法测定斑块破裂处血栓形成的面积,利用光镜观察破裂斑块的形态学特征,采用免疫组化方法测定巨噬细胞的蛋白表达,原位杂交方法分别测定COX-2 mRNA和MMP-2 mRNA表达。结果阿司匹林5mg·kg-1和10mg·kg-1组可以抑制粥样斑块破裂处血栓的形成(P<0.01,P<0.05),且5mg·kg-1组的作用更明显;阿司匹林可以抑制斑块中泡沫细胞的形成和聚集,使纤维帽尤其是肩部区的结构保持得较为完整;阿司匹林5~10mg·kg-1可明显减少斑块内巨噬细胞数目(P<0.05),也能降低斑块中COX-2 mRNA的表达,且随着剂量的增加作用增强,在10~20mg·kg-1组的作用较为明显(P<0.05),还能明显降低粥样斑块中MMP-2 mRNA表达,但以阿司匹林5mg·kg-1组的作用较好(P<0.05)。结论阿司匹林可通过降低粥样斑块中MMP-2的表达增加动脉粥样斑块的稳定性。     

雷公藤茎、叶的抗炎镇痛药理作用研究

雷公藤叶吕提取物４００、２００ｍｇ／ｋｇｉ．ｇ给药,可明显减轻角又菜胶引起大鼠足跖肿胀和二甲苯引起小鼠耳廓的肿胀作用,对醋酸和小鼠扭体反应有明显抑制作用,表明雷公藤叶具有明显的抗炎,镇痛作用。     

Toxicity of Secalonic acid D

Toxicity of secalonic acid D was examined by using lethality, growth retardation, and histopathology as indexes. The ip LD50 values of 37, 31, and 27 mg/kg were obtained for Charles River CD-1, Texas (ICR), and Sprague-Dawley (CF-1) strains of mice, respectively. The ip LD50 was 52 mg/kg in female CD-1 mice. The iv LD50 was 25 mg/kg in CD-1 male mice. Oral LD50 values of 400 mg/kg in male CD-1 mice and 25 and greater than 400 mg/kg in Sprague-Dawley day-old and weanling (21 d) rats of both sexes, respectively, were obtained. Doses of 20 mg/kg or more ip retarded growth and doses of 30 mg/kg or more ip were lethal to CD-1 mice. Oral doses required to produce such effects in day-old rats were 5 and 20 mg/kg (or higher), respectively. All ip doses of secalonic acid D caused pulmonary atelectases and foccal peritonitis in male CD-1 mice. The latter involved surfaces of abdominal viscera and produced limited subcapsular necrosis of hepatic parenchyma. Exposure to a single lethal dose iv (25 mg/kg or more) of secalonic acid D caused limited hepatic portal necrosis but no peritonitis or other associated local effects observed in CD-1 male mice after ip exposure. Cytoplasmic liposis and loss of glycogen and RNA from hepatocytes were observed in a single mouse receiving 50 mg/kg iv. Death resulting from cardiac and/or pulmonary insufficiency was suggested by atelectasis, pulmonary hemorrhages and edema, and massive atrial dilation in mice that died after lethal ip or iv doses of secalonic acid D. Five daily sublethal ip doses in CD-1 male mice resulted in dose-dependent mortality (LD50, 11.5 mg/kg) indicating cumulative effects.     

白介素-2的抗炎作用和免疫调节作用

研究重组人白介素-2(rhI卜2)的抗炎和免疫调节作用。选择小鼠鼠耳肿胀和大鼠足拓肿胀模型研究，hlL-2的抗炎作用；选择碳廓清率实验、迟发性变态反应实验研究rhIL2的免疫调节作用。RhlL-2注射液，剂量为20，10，5，2．5．1．25万u／kg时，对小鼠鼠耳肿胀模型有抑制作用，其中剂量为2．5～5万u／kg时，抑制率最大；剂量为2．5万u／kg时，对大鼠足拓肿胀模型有显著的抑制作用；rhIL-2注射液每日SC用药剂量为10万u／kg，连续给药9d后，可以明显增强小鼠单核吞噬细胞功能；rhIL-2注射液每日SC用药剂量为5万u／kg，连续给药6d后，可明显减轻由免疫抑制剂引起的小鼠迟发性变态反应降低的强度。rhIL-2在一定剂量范围内可以起到抗炎和免疫调节作用。     

注射用羟基红花黄色素A对家兔血小板聚集、超微结构及血小板活化因子诱导后富血小板血浆中GMP-140含量的影响

目的:观察注射用羟基红花黄色素A(HSYA)对家兔血小板聚集功能及超微结构的影响。方法:采用体内实验法,观察3种剂量的注射用HSYA(10、5和2.5mg/kg)对由花生四烯酸(AA)、二磷酸腺苷(ADP)和血小板活化因子(PAF)(3.6nmol/L)诱导的家兔血小板聚集作用的影响,以及血小板超微结构的变化;并单独研究了以PAF为诱导剂的情况下,富血小板血浆(PRP)中α-颗粒膜蛋白-140(GMP-140)的含量。结果:各剂量HSYA注射剂能抑制AA、PAF诱导的家兔血小板聚集(P<0.05,P<0.01);扫描电镜显示:各剂量HSYA注射剂能减少AA和PAF诱导后的聚集型血小板数量并使树突型血小板突起变少变短(P<0.05,P<0.01);另外,各剂量HSYA注射剂还能降低经PAF诱导后GMP-140的含量(P<0.01)。结论:注射用羟基红花黄色素A具有显著的抗PAF诱导的血小板聚集作用,抑制血小板的活化,从而为临床抗血小板聚集药物的使用提供更多选择。     

Synergistic effect of peplomycin in combination with bleomycin on L5178y mouse lymphoma cells in vivo

Studying the treatment of NMRI mice with ip injections of bleomycin (BLM) for 5 days we found an approximate LD50 of 35 mg/kg; the toxicity of peplomycin (PEP) was slightly higher (LD50: approximately 25 mg/kg). The effect of the two drugs on growth of L5178y mouse lymphoma cells in NMRI mice was examined. BLM alone caused at a concentration of 2.5 mg/kg an almost complete inhibition of tumor cell growth; the same effect was determined with 1 mg PEP/kg. At these concentrations the drugs caused an increase of the survival time of 110% (BLM) or 104% (PEP). Given in combination, one-sixth of the optimal doses yielded an 100% increase of the median survival time. These results indicate a significant synergistic activity of the PEP-BLM combination on L5178y cell growth in vivo (FIC index: 0.34).     

Acute toxicity profile of maprotiline in the rat

The aim of the present study was to examine the toxic effects of single oral administrations of the antidepressant maprotiline at 150 mg/kg or 300 mg/kg using female Sprague-Dawley rats. Body-weight gain was significantly reduced in the group receiving 300 mg/kg on days 1-5 of the study (P<0.01). A significant reduction in food and water intake was observed on days 1 and 2 of the study (P<0.01) in the 300 mg/kg group and on day 1 in the 150 mg/kg group (P<0.05). There was a significant decrease in nocturnal home cage activity over the first five days of the study in the 300 mg/kg group (P<0.01). A significant hypothermic response was observed in both 150 and 300 mg/kg groups at 1, 2 and 4 hr after dosing (P<0.01), that had returned to control values within 8 hr following administration. This study demonstrates that a multi-parameter approach is appropriate for the investigation of high doses of antidepressants in rodents.     

Acute Toxicity of Three New Selective COMT Inhibitors in Mice with Special Emphasis on Interactions with Drugs Increasing Catecholaminergic Neurotransmission

Abstract: 3-Nitropyrocatechols are very potent and selective inhibitors of catechol-O-methyltransferase (COMT). LD50 values of three of these compounds were assessed after intraperitoneal administration with a special emphasis on interactions with drugs increasing catecholaminergic neurotransmission. LD50 values of the inhibitors varied from 137 mg/kg (Ro 41–0960. to 507 mg/kg (OR-462) and 544 mg/kg (OR-611). The LD50 value of Ro 41–096. was significantly lower than that of OR-462 and OR-611 (P<0.05). At toxic dose levels all inhibitors caused convulsions and hypomotility. OR-462 and OR-611 had statistically significant mortality increasing interaction with 20 mg/kg of nomifensine (P<0.05) and the former also with 10 mg/kg of amphetamine (P<0.05). Owing to their high therapeutic indexes these compounds can be considered useful new tools in pharmacological research.