马来酸三甲氧苯丁氨酯的镇痛作用

研究马来酸三甲氧苯丁氨酯（ＴＭ）的镇痛作用，结果显示，腹腔注射ＴＭ２４５、３５０、５００ｍｇ／ｋｇ能显著抑制小鼠扭体反应，５０、７０ｍｇ／ｋｇ能显著提高小鼠热板反应痛阈值，３５、５０、７０ｍｇ／ｋｇ则能够显著提高小鼠压尾痛阈值并减少甲醛致痛评分值，３７５、７００ｍｇ／ｋｇ可显著提高大鼠电刺激痛阈值．连续给小鼠腹腔注射ＴＭ７０ｍｇ／ｋｇ７天，每天用热板法测定小鼠痛阈值，表明其镇痛作用无耐受性．     

合成鱼腥草素对小鼠免疫功能的影响

对于脾切除致免疫功能低下小鼠,合成鱼腥草素（ＨＯＵ）６０ｍｇ／ｋｇ,１２０ｍｇ／ｋｇ灌胃给药均能增强其腹腔巨噬细胞的吞噬功能（Ｐ＜０００１）;迟发型超敏反应强度（Ｐ＜０００１）;明显提高血清溶血素水平（Ｐ＜００５;Ｐ＜０００１）;外周血淋巴细胞ＡＮＡＥ阳性百分率（Ｐ＜０００１）;ＨＯＵ６０ｍｇ／ｋｇ还能明显提高脾切小鼠腹股沟淋巴结中淋巴细胞个数（Ｐ＜００１）,表明ＨＯＵ对脾切除致免疫功能低下小鼠的特异性、非特异性免疫功能均有明显增强作用．     

云南产螺旋藻多糖的分离纯化及其生物活性的初步研究

从云南产螺旋藻中分离纯化出螺旋藻多糖（ＰＳＰ）。腹腔内注射ＰＳＰ１５０ｍｇ／ｋｇ能显著增加小鼠脾重，促进小鼠腹腔ＭΦ吞噬功能及小鼠血清溶血素的形成。并对环磷酰胺所致小鼠免疫器官萎缩、白细胞减少、腹腔ＭΦ吞噬功能降低及血清溶血素形成减少等有明显对抗作用。     

盐酸关附甲素注射液对实验性心律失常的作用

关附甲素是从关白附子块根中提取的一种新生物碱。实验表明ＩＧＦＡＨ（５０　ｇ／ｍｌ）对大鼠离体心脏结扎冠脉诱发的室性心律失常有明显的保护作用，ＩＧＦＡＨ３、６、１２ｍｇ／ｋｇｉｖ能显著提高电刺激麻醉兔心室致颤阈值，ＩＧＰＡＨ１３．４，１６．８，２１．０ｍｇ／ｋｇｉｖ能明显对抗Ｃａｌ２－Ａｃｈ液诱发小鼠房扑（颤），其ＥＤ５０为１２．４±１．５ｍｇ／ｋｇ。ＩＧＦＡＨ１０，２５，４０ｍｇ／ｋｇｉｖ对乌头碱诱发的大鼠室性心律失常有明显的保护作用。ＩＧＦＡＨ小鼠ｉｖ的ＬＤ５０为１６３．９ｍｇ／ｋｇ，其９６％可信限为１５１．９—１７６．７ｍｇ／ｋｇ。     

烟碱对M受体激动剂抑制自发活动的调节

间隔１０ｍｉｎ两次ｉｐ烟碱０．０２和０．２０ｍｇ·ｋｇ－１，小鼠对烟碱抑制自发活动的作用产生急性耐受，使Ｍ受体激动剂氧化震颤素５０μｇ·ｋｇ－１抑制自发活动的作用显著增强．间隔５ｍｉｎ两次ｉｐ烟碱０．２５和０．５０ｍｇ·ｋｇ－１，大鼠对烟碱抑制自发活动的作用产生急性耐受，使Ｍ受体激动剂槟榔碱５ｍｇ·ｋｇ－１抑制自发活动的作用也显著增强．提示反复注射烟碱诱导动物对烟碱急性耐受后，Ｍ受体激动剂抑制自发活动的作用显著增强．     

淫羊藿总黄酮的免疫调节作用

淫羊藿总黄酮４００ｍｇ／ｋｇ显著增加正常小鼠单核巨噬细胞的吞噬功能,提高血清溶血素抗体生成水平,对迟发型超敏反应强度无明显影响;２００ｍｇ／ｋｇ,４００ｍｇ／ｋｇ可显著拮抗环磷酰胺所致小鼠单核巨噬细胞吞噬能力,血清溶血素抗体生成水平和迟发型超敏反应强度降低;２００ｍｇ／ｋｇ可显著降低致敏前给予环磷酰胺所致的迟发型超敏反应增强．进一步研究表明;淫羊藿总黄酮的免疫调节作用与其对ＴＨ／ＴＳ比值的调节作用有关．     

醋己氨酸锌的抗胃溃疡作用

目的：观察醋己氨酸锌（ＺＡ）抗大鼠或小鼠实验性胃溃疡作用。方法与结果：设ＺＡ，雷尼替丁（Ｒａｎ）和空白对照组。ＺＡ２５，５０，１００ｍｇ／ｋｇ，ｉｐ和Ｒａｎ１２．５，２５，５０ｍｇ／ｋｇｉｐ均能明显降低幽门结扎大鼠的胃酸和胃蛋白酶活力（Ｐ＜０．０１），ＺＡ还能明显提高胃液中己糖胺含量，对ＨＣｌ０．６ｍｏｌ／Ｌ，２５％ＮａＣｌ和无水乙醇所致小鼠胃溃疡有明显的阻抑作用，ＺＡｉｇ７５－３００ｍｇ／ｋｇ明显抑制大鼠冷应激和束水应激诱发的胃溃疡及胃粘膜肥大细胞数的下降，但Ｒａｎ对后者没有抑制作用。结论：ＺＡ对大鼠或小鼠实验性胃溃疡有明显的阻抑作用。     

蝎毒多肽的镇痛及抗炎作用

采用热板法和醋酸扭体法证明腹腔注射蝎毒多肽０．６５０，０．４３３ｍｇ／ｋｇ能明显升高小鼠痛阈和减少小鼠的扭体次数．腹腔注射蝎毒多肽０．４３３，０．２１６ｍｇ／ｋｇ能明显对抗蛋清所致的大鼠足肿胀；连续７天腹腔注射蝎毒多肽０．２６０，０．１３０ｍｇ／ｋｇ能明显抑制大鼠棉球肉芽肿形成；腹腔注射蝎毒多肽０．６５０，０．４３３ｍｇ／ｋｇ能降低小鼠腹腔毛细血管通透性     

五灵脂乙酸乙酯提取物抗炎作用研究

五灵脂乙酸乙酯提取物（ＷＬＺ）腹腔注射４００ｍｇ／ｋｇ对二甲苯所致小鼠耳壳肿胀及对角叉菜胶所致大鼠足跖肿胀有显著抑制作用；灌胃６００ｍｇ／ｋｇ能明显抑制由醋酸引起的小鼠腹腔毛细血管渗出；腹腔注射８００ｍｇ／ｋｇ对小鼠棉球肉芽组织增生有明显抑制作用．ＷＬＺ能显著降低炎症组织的前列腺素Ｅ（ＰＧＥ）含量，但对小鼠血清皮质酮水平无显著性影响，表明ＷＬＺ的抗炎作用与其抑制ＰＧＥ合成或释放有关．     

蝎毒多肽的镇痛及抗炎和作用

采用热板法和醋酸扭体法证明腹腔注射蝎毒多肽０．６５０，０．４３３ｍｇ／ｋｇ能明显升高小鼠痛阈和减少小鼠的扭体次数，腹腔注射蝎毒多肽０．４３３，０．２１６ｍｇ／ｋｇ能明显对抗蛋清所致的大鼠中肿用连续７天腹腔注射蝎毒多肽０．２６０，０．１３０ｍｇ／ｋｇ能明显抑制大鼠棉球肉芽肿形成；腹腔注射蝎毒多肽０．６５０，０．４３３ｍｇ／ｋｇ能降低小鼠腹腔毛细血管通透性。     

赖氨酸锗和环磷酰胺合用对小鼠S-180肉瘤抑瘤作用

赖氨酸锗(Ge401)是国内新近研制的含微量元素锗有机物。测得小鼠gi LD_(50)为9.26g/kg,ip LD_(50)为5.62g/kg;采用ig、ip、iv途径给药,对小鼠S-180肉瘤均有显著抑瘤作用,其中iv给药的抑瘤率(55%)最高;Ge401(30mg/kg·5d~(-1))和环磷酰胺(30mg/kg·2d~(-1))合用具有明显增强抑瘤作用。     

Cyclophosphamide treatment causes impairment of sperm and its fertilizing ability in mice

This study is focused on the toxicological effect of cyclophosphamide on male mice reproductive system. In the present study, cyclophosphamide was injected intraperitoneally (ip) at the level of 50-200mg/kg body weight into 6-weeks old ICR male mice once in a week for a period of 5 weeks. The animals were sacrificed after 1st and 5th week of last injection. Reduction in weight of testis and epididymis were observed both in 1st and 5th week group mice after administration with increasing concentration of cyclophosphamide. The weight of the body significantly decreased in both 1st and 5th week group in mice treated with 200mg/kg cyclophosphamide. The weight of the testis significantly decreased with all doses of cyclophosphamide in 1st week group, whereas, in 5th week group significant reduction was observed only in 200mg/kg dose of cyclophosphamide. The sperm motility was analyzed with Computer-Assisted Sperm Analysis (CASA). The motility of caudal sperm decreased with increasing concentration of cyclophosphamide in the 1st week group, whereas, it revived after 5th week. The total sperm counts in the epididymis of 1st week group mice declined significantly while significant restoration of the same was observed with mice treated with 50,100 and 150 mg/kg doses in the 5th week group. The intact acrosome was lower with 150 and 200mg/kg doses in both 1st and 5th week group. The live sperm was reduced to 29% in mice treated with 200mg/kg in the 5th week group. The decrease in the pregnancy rate of female mice was 17, 50, 58 and 100% when mated with male mice injected with 50, 100, 150 and 200mg/kg dose, respectively. Seminiferous tubules of mouse testis were severely damaged in the 1st week group. However, reinstate of sperm within the seminiferous tubules was observed in the 5th week group mice. Significant decrease in serum luteinizing hormone (LH) was observed in the 1st week group treated with 50, 100, 150 and 200mg/kg dose of cyclophosphamide. However, no significant difference was observed in the serum follicle-stimulating hormone (FSH), whereas, a decrease of about 98% in serum testosterone level was observed in cyclophosphamide treated mice. The decrease in the mean testosterone levels of cyclophosphamide treated mice served as proof for the damage of testis. These results demonstrate that cyclophosphamide caused temporary interference of normal male reproductive system with low dose treatment, but might be permanent dysfunction in high dose treatment.     

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.     

Behavioural pharmacology of polygalasaponins indicates potential antipsychotic efficacy.

Polygalasaponins were extracted from a plant (Polygala tenuifolia Willdenow) that has been prescribed for hundreds of years to treat psychotic illnesses in Korean traditional medicine. Previous in vitro binding studies suggested a potential mechanism for its antipsychotic action, as polygalasaponin was shown to have an affinity for both dopamine and serotonin receptors [Psychopharmacol. Bull. 31 (1995) 139.]. In the present study we have investigated the functional in vivo actions of this material in tests that are predictive of dopamine and serotonin antagonist activities. Polygalasaponin (25-500 mg/kg) was shown to produce a dose-related reduction in the apomorphine-induced climbing behaviour (minimum effective dose [ED(min)] 25 mg/kg ip, 250 mg/kg sc and po), the 5-hydroxytryptamine (5-HTP)-induced serotonin syndrome (ED(min) 50 mg/kg ip) and the MK-801-induced hyperactivity (ED(min) 25 mg/kg ip) in mice. This compound also reduced the cocaine-induced hyperactivity (ED(min) 25 mg/kg ip) in rats. These results demonstrated that polygalasaponin has dopamine and serotonin receptor antagonist properties in vivo. This might suggest its possible utility as an antipsychotic agent.     

Toxicologic evaluation of injectable acemannan in the mouse, rat and dog.

Acemannan, the USAN-accepted name for long-chain polydispersed beta-(1,4)-acetylated polymannose with interspersed 0-acetyl groups with a mannose monomer/acetyl ratio of approximately 1:1 and extracted from Aloe vera (barbadensis Miller), was administered as a 1.0 mg/ml solution to mice, rats and dogs, either as single dose or repeated at 4-d intervals for 8 doses by iv or ip routes. No significant signs of intoxication and no deaths occurred in animals treated with the single injection of acemannan at dosages of 80 mg/kg iv or 200 mg/kg ip in mice, 15 mg/kg iv or 50 mg/kg ip in rats, and 10 mg/kg iv or 50 mg/kg ip in dogs. On repeated injections systemic toxicity was limited to obvious transient discomfort that appeared dose related. There was accumulation of macrophages and monocytes without subsequent inflammatory reaction in lungs of the iv-treated animals, and in liver and spleen and on peritoneal surfaces of ip-treated animals. The effects were not considered adverse, but were consistent with the known immune stimulating activity of acemannan. A few deaths occurred in mice and rats that were suggestive of resulting from improper injection or sequella of necrosis of the injection site. The NOAELs for acemannan determined from these repeated injection studies were 20 mg/kg iv or ip in the mouse, 4.0 mg/kg iv and 50 mg/kg ip in the rat, and 1.0 mg/kg iv in dogs; 5.0 mg acemannan/kg ip in the dog was considered to be LOAEL, based on the emesis and abdominal discomfort induced.     

Antineoplastic activity of ASTA Z 7557 (NSC-345842, INN mafosfamide) on transplantable murine tumors

Summary The antitumor activity of ASTA Z 7557, a stabilized primary metabolite of cyclophosphamide, was evaluated in comparison with cyclophosphamide (CP) against different rodent tumor systems. At equimolar doses, which corresponded in mg/kg to the optimal doses of each compound, Z 7557 showed a higher therapeutic activity than CP when both drugs were administered intraperitoneally (ip) during 5 consecutive days. The drug remained active against a P388 subline totally resistant to CP, but to a much lesser extent. The ipimplanted B16 melanoma was highly sensitive to 100 and 50 mg/kg administered during 9 consecutive days: an increase in lifespan (ILS) of 244% was produced and 5 mice out of 10 were cured. This treatment administered against Lewis lung carcinoma (LL) transplanted intravenously (iv) induced an ILS of 179% and 3 mice out of 10 survived on day 60. This effect was slightly inferior to that produced by 50 mg/kg of CP, but is balanced by the number of long-term survivors recorded after administration of low doses of Z 7557. When mice bearing the subcutaneously (sc) implanted colon 38 (C38) tumor were treated with 200 mg/kg on days 2 and 9, the tumor growth was inhibited by 83% in comparison to the control mice. The wide range of activity of Z 7557, its stability and its different chemical reactivity as compared to CP appear to justify interest in this activated oxazaphosphorine.     

7-Nitroindazole, but not NG-nitro-L-arginine, enhances the anticonvulsant activity of pregabalin in the mouse maximal electroshock-induced seizure model

The objective of this study was to determine the effects of 7-nitroindazole (7NI--a preferential neuronal nitric oxide synthase (NOS) inhibitor) and NG-nitro-L-arginine (NNA--a non-selective NOS inhibitor) on the anticonvulsant action of pregabalin (PGB--a third-generation antiepileptic drug) in the maximal electroshock (MES)-induced seizure model in mice. Electroconvulsions were produced in mice by means of an alternating current (50 Hz, 500 V, 25 mA, ear-clip electrodes, 0.2 s stimulus duration, tonic hindlimb extension taken as the endpoint). The anticonvulsant action of PGB in the MES test was expressed as median effective doses (ED50 values) of the drug, protecting 50% of animals tested against MES-induced seizures. The acute adverse-effect potentials of PGB in combination with 7NI and NNA were evaluated in the chimney test (motor coordination), step-through passive avoidance task (long-term memory) and grip-strength test (skeletal muscular strength) in mice. 7NI (50 mg/kg, ip) significantly enhanced the anticonvulsant action of PGB by reducing the ED50 value of PGB from 145.0 mg/kg to 74.4 mg/kg (p<0.01). Similarly, 7NI at the lower dose of 25 mg/kg also potentiated the anticonvulsant action of PGB by lowering the ED50 value of PGB from 145.0 mg/kg to 117.9 mg/kg, although the results did not attain statistical significance. In contrast, NNA (40 mg/kg, ip) had no impact on the anticonvulsant effects of PGB. Moreover, none of the examined combinations of PGB with 7NI and NNA affected motor coordination, long-term memory and skeletal muscular strength in mice. Based on this preclinical study, one can conclude that 7NI significantly enhanced and NNA had no effect on the anticonvulsant activity of PGB against MES-induced seizures in mice.     

螺旋藻多糖对环磷酰胺所致小鼠骨髓抑制的实验研究

目的研究螺旋藻多糖对小鼠骨髓造血功能的增强作用。方法将小鼠分成4组对照组、环磷酰胺模型组、螺旋藻多糖30mg