白芷香豆素的镇痛作用部位及其机制

目的 观察白芷香豆素(Coumarin of Angelicae Dahuricae,CAD)的镇痛作用部位及其机制.方法 利用小鼠福尔马林实验及侧脑室注射CAD对小鼠热板痛反应潜伏期的影响以分析CAD的镇痛作用部位;观察CAD对甲醛所致伤害性疼痛模型小鼠血清一氧化氮(NO)和脑组织中β-内啡肽(β-EP)含量的影响.结果 CAD(30,60,120 mg/kg)不同程度地抑制了小鼠福尔马林实验第一和第二时相反应.侧脑室注射CAD(6 mg/kg)明显延长小鼠热板痛反应潜伏期.CAD(30,60,120 mg/kg)连续给药4 d,使甲醛所致伤害性疼痛模型小鼠血清NO含量和脑中β-EP含量明显下降.结论 CAD对物理、化学等伤害性刺激具有明显镇痛作用,作用部位可能既在中枢也在外周,镇痛机制可能与抑制NO的合成或释放有关.     

熊果酸纳米脂质体的镇痛作用和抗炎活性

目的探讨熊果酸（UA）纳米脂质体的镇痛作用和抗炎活性。方法取昆明种小鼠若干只,随机分为生理盐水组、UA纳米脂质体低剂量组（9mg／kg）、UA纳米脂质体中剂量组（13．5mg／kg）、UA纳米脂质体高剂量组（18mg／kg）、安痛定组。采用醋酸扭体法、小鼠热板法评价UA的镇痛活性,采用甲醛致炎法评价UA的抗炎活性。结果UA纳米脂质体各剂量组小鼠扭体次数与生理盐水对照组比较明显减少,痛域明显提高,差异均有统计学意义（P〈0．05或〈0．01）。UA各剂量组与生理盐水对照组比较,甲醛致炎实验第2时相小鼠抬腿抖足次数明显减少（P〈0．05或〈0．01）。结论UA纳米脂质体具有一定的镇痛和抗炎活性。     

美洲大蠊提取物抗炎、镇痛作用的实验研究

目的本实验就美洲大蠊提取物的抗炎、镇痛等药理作用进行动物实验研究。方法采用二甲苯致小鼠耳廓肿胀和蛋清致大鼠足跖肿胀两种动物模型,考察美洲大蠊提取物抗炎作用;采用小鼠热板法镇痛试验及醋酸致小鼠扭体反应模型以考察其镇痛的效果。结果美洲大蠊提取物可抑制二甲苯所致的小鼠耳廓肿（P〈0.05）、蛋清所致的大鼠足跖肿胀（P〈0.05）,可使醋酸所致的扭体次数明显减少（P〈0.05）,并使小鼠热板法痛阈明显提高（P〈0.01）。结论初步证明美洲大蠊提取物具有抗炎消肿、镇痛的作用。     

利脑宁镇痛作用的药效学研究

目的研究中药复方制剂利脑宁的镇痛作用,为该药的临床应用提供理论依据。方法通过小鼠扭体法、小鼠热板法、大鼠电刺激法进行镇痛实验。结果利脑宁可显著抑制醋酸所致小鼠扭体反应,可提高热板法所致小鼠的痛阈及大鼠电刺激法所致的痛阈,其作用强度呈剂量依赖性。结论利脑宁具有镇痛作用。     

阿魏酸钠对结肠炎大鼠结肠巨噬细胞功能的影响

目的探讨阿魏酸钠在整体水平对结肠炎大鼠结肠巨噬细胞功能的影响及其机制。方法建立大鼠免疫性结肠炎模型。阿魏酸钠（SF）灌肠用药21d后检测结肠组织MDA、NO、PGE2含量，SOD、IL-1，TNF-α、MPO活性及NF-κB p65表达水平。结果阿魏酸钠（200，400，800mg／kg）灌肠后呈剂量依赖型降低模型组大鼠的MDA、NO、PGE2含量，IL-1、TNF—α、MPO活性及NF-κB p65表达水平，同时升高SOD活性。结论SF可减弱结肠炎大鼠结肠活化巨噬细胞的生物活性，缓解结肠炎症反应，机制可能与抑制NF-κB表达有关。     

通城虎镇痛抗炎作用及急性毒性的实验研究

目的 研究通城虎的镇痛抗炎作用并进行它的急性毒性试验.方法 采用醋酸致扭体反应、热板法测定痛阈,观察通城虎的镇痛作用;抗炎实验采用二甲苯致鼠耳肿胀法、角叉菜胶致大鼠足趾肿胀法和腹腔毛细血管通透性法;采用Bliss法测定了其半数致死量(LD50).结果 通城虎能减少醋酸所致小鼠扭体次数,明显提高小鼠的痛阈;抑制二甲苯所致小鼠耳廓肿胀、角叉菜胶引起的大鼠足趾肿胀和醋酸所致小鼠腹腔毛细血管通透性增加;其LD50为100.1 g/kg,LD50的95%可信限为87.2 ～115.1 g/kg.结论 通城虎对实验动物模型具有显著的镇痛抗炎作用,使用时一定要注意其不良反应.     

白芷香豆素的镇痛作用和身体依赖性研究

目的 观察白芷香豆素(CAD)的镇痛作用和身体依赖性.方法 采用热板法、扭体法观察CAD的镇痛作用;用小鼠跳跃反应实验、小鼠竖尾反应实验观察CAD的身体依赖性,并用耐受性实验考察其耐受性.结果 CAD 30、60、120 mg/kg对物理、化学等伤害性刺激的镇痛作用确切,作用维持时间长;小鼠跳跃反应实验表明,吗啡组小鼠出现明显的跳跃反应,而CAD组则无;小鼠竖尾反应实验表明CAD组小鼠未出现竖尾反应;耐受性实验表明连续应用CAD不易出现耐受性.结论 CAD具有明显的镇痛作用且对小鼠无身体依赖性作用.     

琼枝麒麟菜多糖对衰老模型小鼠血浆和肝中SOD、CAT、MDA的影响

目的 探讨琼枝麒麟菜多糖（Eucheuma gelatinae polysaccharide,EGP）对衰老模型小鼠氧化自由基的影响.方法 检测小鼠血浆和肝脏超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和丙二醛（MDA）并进行对比分析.结果 200 mg/kg和400 mg/kg的EGP不仅能明显降低衰老模型小鼠血清和肝脏的MDA含量,而且能够提高SOD和CAT活性,并呈剂量依赖性增强.100 mg/kg的EGP对衰老模型小鼠肝脏SOD、小鼠血浆和肝脏CAT也有明显的促进作用.结论 琼枝麒麟菜多糖具有清除衰老模型小鼠自由基和抑制脂质过氧化的作用.     

乌头注射液对疼痛小鼠的镇痛作用

目的观察乌头注射液在多种疼痛模型下的镇痛作用。方法 ICR小鼠随机分为对照组,乌头注射液低、中、高剂量(0.5、1.0、2.0 mg/kg)组,阳性对照药益赛普组(14 mg/kg);对照组和益赛普组于实验第1、4天皮下注射给药,乌头注射液各组肌肉注射给药,连续7 d。Wistar大鼠随机分为对照组,乌头注射液低、中、高剂量(0.4、0.8、1.6 mg/kg)组,阳性对照药益赛普(10 mg/kg)组;对照组和益赛普组于实验第1、4天皮下注射给药。乌头注射液各组肌肉注射给药,连续7 d。采用小鼠醋酸扭体实验、小鼠热板实验、大鼠光热致痛甩尾实验3个疼痛模型,研究乌头注射液的镇痛作用。结果乌头注射液能显著减少醋酸引起的小鼠扭体次数,提高小鼠热板法和大鼠光热致痛法痛阈。结论乌头注射液对多种疼痛模型均具有明显对抗作用。     

芡实超微粉的小鼠体内延缓衰老功效

目的研究芡实超微粉对D-半乳糖致衰老小鼠的抗衰老作用。方法将60只小鼠随机分为正常组、衰老模型组、维生素(V)E组(100 mg/kg)及芡实低(300 mg/kg)、中(600 mg/kg)、高(1 200 mg/kg)剂量组。通过腹腔注射200 mg/(kg·d)的D-半乳糖建立衰老小鼠模型,同时每天灌胃相应药物。给药6 w后测定各组血清、肝脏和脑组织中丙二醛(MDA)、一氧化氮(NO)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、总抗氧化能力(T-AOC)水平和端粒酶含量及脏器指数。结果芡实超微粉能显著降低小鼠机体MDA和NO含量,显著提高SOD、GSH-Px活性和T-AOC水平,显著提高端粒酶含量及拮抗脑萎缩。结论芡实超微粉具有良好的体内延缓衰老功效。     

Blockade of tolerance to morphine but not to kappa opioids by a nitric oxide synthase inhibitor.

The nitric oxide synthase inhibitor NG-nitro-L-arginine (NO2Arg) blocks morphine tolerance in mice. After implantation of morphine pellets the analgesic response decreases from 100% on the first day to 0% on the third. Coadministration of NO2Arg along with the pellets markedly retards the development of tolerance; 60% of mice are analgesic after 3 days, and 50% of mice are analgesic after 5 days. In a daily injection paradigm the analgesic response to morphine is reduced from 60% to 0% by 5 days. Concomitant administration of morphine along with NO2Arg at doses of 2 mg/kg per day prevents tolerance for 4 weeks. A single NO2Arg dose retards morphine tolerance for several days, and dosing every 4 days is almost as effective as daily NO2Arg. NO2Arg slowly reverses preexisting tolerance over 5 days despite the continued administration of morphine along with NO2Arg. NO2Arg also reduces dependence and reverses previously established dependence. NO2Arg does not prevent tolerance to analgesia mediated by the kappa 1 agonist trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolindinyl)cyclohexyl]- benzene-acetamide (U50,488H) or the kappa 3 agent naloxone benzoylhydrazone, indicating a selective action of NO in the mechanisms of mu tolerance and dependence.     

Acetaminophen-induced hypothermia in mice is mediated by a prostaglandin endoperoxide synthase 1 gene-derived protein

Acetaminophen is a widely used antipyretic analgesic, reducing fever caused by bacterial and viral infections and by clinical trauma such as cancer or stroke. In rare cases in humans, e.g., in febrile children or HIV or stroke patients, acetaminophen causes hypothermia while therapeutic blood levels of the drug are maintained. In C57/BL6 mice, acetaminophen caused hypothermia that was dose related and maximum (>2 degrees C below normal) with a dose of 300 mg/kg. The reduction and recovery of body temperature was paralleled by a fall of >90% and a subsequent rise of prostaglandin (PG)E(2) concentrations in the brain. In cyclooxygenase (COX)-2(-/-) mice, acetaminophen (300 mg/kg) produced hypothermia accompanied by a reduction in brain PGE(2) levels, whereas in COX-1(-/-) mice, the hypothermia to this dose of acetaminophen was attenuated. The brains of COX-1(-/-) mice had approximately 70% lower levels of PGE(2) than those of WT animals, and these levels were not reduced further by acetaminophen. The putative selective COX-3 inhibitors antipyrine and aminopyrine also reduced basal body temperature and brain PGE(2) levels in normal mice. We propose that acetaminophen is a selective inhibitor of a COX-1 variant and this enzyme is involved in the continual synthesis of PGE(2) that maintains a normal body temperature. Thus, acetaminophen reduces basal body temperature below normal in mice most likely by inhibiting COX-3.     

Influence of Kupffer cells on hepatic signal transduction as demonstrated by second messengers and nuclear transcription factors

AIM: TO understand the influence of Kupffer cell (KC) on signal transduction pathways in the liver. METHODS: To decrease selectively the number and function of KC, Kunming mice were ip injected with a single dose of gadolinium chloride (GdCl3, 20mg.kg^-1), the time-effect relationship assessment was performed after 1d, 3d and 6d. sALT, sGST, liver glycogen content, phagocytic index, and expression of CD68 were assessed as the indexes of hepatotoxicity and functions of KC respectively, and morphology of KC was observed with transmission electron microscopy. Furthermore, cAMP, PGE2 level, nitric oxide(NO) content, and mRNA expression of NFkappaBp65, Erkl, STAT1were examined. RESULTS: GdCI3 could selectively cause apoptosis of KC and obvious reduction of KC‘‘s activity, but no hepatotoxicity was observed. One day after KC blockade, NO, PGE2, cAMP contents in the liver were reduced 21.0 %, 6.94-fold, 8.3%, respectively, and mRNA expression of NFkappaBp65 was decreased 3.0-fold. The change tendency of NO, PGE2, and cAMP contents and mRNA expression of NFkappaBp65 were concomitant with recovery of the functions of KC. The contents of NO, PEG2, cAMP were increased when the functions of KC was recovered. However, all of the changes could not return to the normal level except NO content after 6 d Gdcl3 treatment. No obvious changes were found in STAT1 and Erkl mRNA expression in thepresent study. CONCLUSION: Hepatic NO, PGE2, cAMP level and mRNA expression of NFkappaBp65 are closely related with the status of KC. It suggests that KC may play an important role in the cell to cell signal transduction in the liver.     

Pharmacological properties of a potent and selective nonpeptide substance P antagonist.

We describe here the pharmacological properties of RP 67580 [(3aR,7aR)-7,7-diphenyl-2-[1-imino-2-(2-methoxyphenyl)ethyl] perhydroisoindol-4-one], a nonpeptide antagonist of substance P (SP). In vitro, the compound was found to inhibit in a competitive manner (Ki = 4.16 +/- 0.59 nM) [3H]SP binding to neurokinin receptors type 1 (NK1 receptors) in rat brain membranes. Contractions induced by SP and septide (a selective NK1 agonist) in guinea pig ileum were competitively inhibited by RP 67580 (pA2 = 7.16 and 7.59, respectively). Moreover, RP 67580 displayed the profile of a specific antagonist of NK1 receptors: it was not active on NK2 and NK3 receptors as seen in binding assays and in isolated preparations of rabbit pulmonary artery and rat portal vein. In the rat, low intravenous doses of RP 67580 totally inhibited the plasma extravasation induced by SP in the urinary bladder (ED50 = 0.04 mg/kg i.v.) and by antidromic electrical stimulation of the saphenous nerve in the hind paw skin (ED50 = 0.15 mg/kg i.v.). This compound was also active in two classical analgesic tests in mice: phenylbenzoquinone-induced writhing (ED50 = 0.07 mg/kg s.c.) and the formalin test (ED50 = 3.7 mg/kg s.c.). Its potency was of the same order as that of morphine. Thus we conclude that RP 67580, a SP antagonist, belongs to a class of drugs that may be useful in the management of various clinical pathologies where pain and neurogenic inflammation are involved.     

Role of bradykinin, nitric oxide, and angiotensin II type 2 receptor in imidapril-induced angiogenesis

The angiotensin II (Ang II)-Ang II type 1 receptor pathway is proangiogenic, whereas studies showed that some angiotensin-converting enzyme inhibitors also stimulate angiogenesis in the setting of tissue ischemia, leaving a controversy of Ang II-mediated angiogenesis. We investigated whether an angiotensin-converting enzyme inhibitor imidapril-induced angiogenesis might be mediated via the tissue bradykinin pathway. To rule out the conventional effects of Ang II on angiogenesis, we used Ang II type 1a receptor knockout (AT1aKO) mice. We examined the effects of the angiotensin-converting enzyme inhibitor imidapril on angiogenesis in a hindlimb ischemia model using AT1aKO mice. After induction of hindlimb ischemia, AT1aKO mice were treated with or without imidapril (1.0 or 0.1 mg/kg per day for 21 days). Angiogenesis was quantified by laser Doppler blood flowmetry and capillary density. Angiogenesis was reduced in AT1aKO mice compared with wild-type mice. Imidapril with either low or high doses enhanced angiogenesis in AT1aKO mice (P<0.01). Ang II type 2 receptor antagonist (PD123319; 30 mg/kg per day) and B1 receptor antagonist (DesArg9-[Leu8]-bradykinin; 50 nmol/kg per day) suppressed the imidapril-induced angiogenesis in AT1aKO mice to an extent even lower than that of nontreated AT1aKO mice. B2 receptor antagonist (Hoechst 140; 100 microg/kg/d) and NO synthase inhibitor (N(G)-nitro-L-arginine methyl ester; 20 mg/kg per day) moderately attenuated the imidapril-mediated angiogenesis. RT-PCR revealed that vascular endothelial growth factor receptor 2 mRNA was reduced with PD123319, DesArg9-[Leu8]-bradykinin, or Hoechst 140, and vascular endothelial growth factor mRNA abundance was suppressed with PD123319 or DesArg9-[Leu8]-bradykinin. In conclusion, imidapril elicited angiogenesis in the setting of tissue ischemia in AT1aKO mice. This angiogenic effect might involve the Ang II-Ang II type 2 receptor pathway in addition to the bradykinin-B1 and bradykinin-B2 receptor/NO-dependent pathways.     

Analgesic effects of crude extracts and fractions of Omani frankincense obtained from traditional medicinal plant Boswellia sacra on animal models

ObjectiveTo investigate the analgesic effect of Boswellia sacra (B. sacra), which could support the Omani traditional uses of frankincense for muscle, stomach, and arthritis pain.MethodsThe crude extract, the essential oils and various sub-fractions of the crude methanol extract (each 300 mg/kg of the body weight of the animal) obtained from the resin of B. sacra were administered orally, and were evaluated for their analgesic activities by using two well known models of pain in mice, viz. acetic acid induced writhing test and formalin induced pain test in mice.ResultsOf 13 samples, almost all of them were effective at an orally administered dose of 300 mg/kg of the body weight. The acetic acid induced writhes were inhibited in all the three phases with comparable values to the standard drug aspirin (300 mg/kg of body weight) with inhibition of 67.6% in phase I, 66.8% in phase II, and 37.9% in phase III. At the same time, all the tested samples were found effective in both the early and the late phases of formalin test. In formalin test, most of the tested samples showed more inhibitory effects as compared to the standard drug aspirin (300 mg/kg of body weight), which showed 36.2% and 29.6% inhibition in early and late phases respectively. Among the tested samples, the most significant inhibition was produced by Shabi frankincense oil (57.5% in early phase, and 55.6% in late phase). Interestingly, the extracts showed comparable percentage of inhibition to the oil and found in the following order: 60% chloroform/n-hexane sub-fraction (55.3% in early phase, and 66.7% in late phase), and 70% chloroform/n-hexane sub-fraction (59.6% in early phase, and 63.0% in late phase).ConclusionsThe present study provided the scientific justification about the analgesic properties of the essential oils, extract, and various sub-fractions obtained from the resin of B. sacra, thus validating its use in traditional folk medicines and other products; and hence supporting the development in the analgesic properties of bioactive natural substances.     

黄芪甲苷对甲状腺功能减退雌性大鼠子宫氧化应激反应的影响

目的观察黄芪甲苷(AST)对甲状腺功能减退雌性大鼠子宫氧化应激反应的影响。方法将60只大鼠[4周龄,体质量(110±10)g],采用随机数表法分为对照组,模型组,AST 20、40、80 mg/kg组和左甲状腺素钠9×10-3 mg/kg组,给予0.1%丙基硫氧嘧啶复制甲状腺功能减退动物模型,以左甲状腺素钠作为阳性对照药,检测各组大鼠血清髓过氧化物酶(MPO)、过氧化氢酶(CAT)活性和一氧化氮(NO)含量;子宫组织超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性,丙二醛(MDA)、乳酸脱氢酶(LDH)含量,钙离子(Ca²⁺)浓度和高能磷酸化合物(HEP)水平;离体子宫平滑肌收缩张力(CT)、收缩频率(CF)和子宫活动力(UM)。采用SPSS 17.0统计软件进行数据分析。多组间比较采用方差分析,组间两两比较采用SNK检验。结果AST组大鼠血清MPO活性和NO含量降低,CAT活性升高(P<0.05);子宫组织中三磷酸腺苷、二磷酸腺苷、一磷酸腺苷、总腺嘌呤核苷酸和SOD、GSH-Px明显升高,LDH和MDA明显降低(P<0.05);离体子宫平滑肌CT、CF、UM以及Ca^(²⁺)浓度均明显升高(P<0.05),以AST 80 mg/kg效果最为显著。结论AST具有抑制甲状腺功能减退雌性大鼠子宫氧化应激损伤的作用,可能与其能够有效改善抗氧化酶活性、开放Ca²⁺通道、增强离体子宫平滑肌的敏感性、并促进能量代谢有关。     

Antiplasmodial and analgesic activities of Clausena anisata

ObjectiveAntiplasmodial and analgesic activities of the leaf extract and fractions of Clausena anisata (C. anisata) were evaluated for antimalarial and analgesic activities.MethodsThe crude leaf extract (39–117 mg/kg) and fractions (chloroform and acqeous; 78 mg/kg) of C. anisata were investigated for antiplasmodial activity against chloroquine-sensitive Plasmodium berghei (P. berghei) infections in mice using suppressive, prophylactic and curative models and analgesic activity against acetic acid, formalin and heat-induced pains. Artesunate, 5 mg/kg and pyrimethamine, 1.2 mg/kg were used as positive controls. Thin films made from tail blood of each mouse were used to assess the level of parasitaemia of the mice.ResultsThe extract and its fractions dose-dependently reduced parasitaemia induced by chloroquine-sensitive P. berghei in prophylactic, suppressive and curative models in mice. These reductions were statistically significant (P<0.001). They also improved the mean survival time (MST) from 17 to 21 days relative to control (P<0.01 ? 0.001). On chemically and thermally-induced pains, the extract inhibited acetic acid and formalin-induced inflammation as well as hot plate-induced pain in mice. These inhibitions were statistically significant (P<0.001) and in a dose-dependent fashion.ConclusionsThe antiplasmodial and analgesic effects of this plant may in part be mediated through its chemical constituents and it can be concluded that the C. anisata possess significant antimalarial and analgesic properties.