杜鹃花总黄酮的镇痛作用研究

目的研究杜鹃花总黄酮（TFR）的镇痛作用及其机制。方法镇痛试验采用小鼠扭体法、小鼠福尔马林试验、小鼠温浴法及小鼠热板法;血清和脑组织匀浆中NO和PGE2含量的测定分别采用Griess法和紫外分光光度法。结果灌胃TFR（100、200 mg／kg）可明显延长小鼠热板舔足反应潜伏期及小鼠热水缩尾时间且明显抑制小鼠福尔马林试验Ⅱ相反应。TFR（50、100 mg／kg）可明显抑制小鼠扭体反应数;100 mg／kgTFR能升高小鼠血清中NO的含量,200 mg／kg TFR能升高脑组织中NO的含量。TFR可明显降低小鼠脑组织PGE2含量,100 mg／kg可降低血清中PGE2含量。结论TFR具有明显镇痛作用,其镇痛作用机制可能为促进NO释放及抑制PGE2合成。     

蒺藜皂苷对β-淀粉样肽(25-35)所致衰老小鼠学习记忆障碍的改善作用及其机制

目的 研究蒺藜皂苷对凝聚态β-淀粉样肽(25～35)(Aβ25～35)致小鼠学习记忆障碍的改善作用及探讨其可能的作用机制.方法 采用一次性小鼠右侧脑室注射Aβ25～35 3 μl造成AD小鼠模型,应用避暗实验、Morris水迷宫实验观察腹腔注射蒺藜皂苷(50,150,450 mg/kg)对Aβ25～35模型小鼠记忆障碍的改善作用,并于侧脑室注射后14 d测定各组小鼠脑组织中一氧化氮(NO)含量及一氧化氮合酶(NOS)、诱导型一氧化氮合酶( iNOS)的活性.结果 单侧侧脑室一次注射Aβ25～35 3 μl可引起小鼠学习记忆障碍,同时使小鼠脑组织内NO含量增加, NOS和iNOS活性显著升高,而连续注射蒺藜皂苷14 d治疗后,可不同程度改善Aβ25～35造成的学习记忆障碍,同时蒺藜皂苷50 mg/kg治疗组可显著降低NO含量和NOS、iNOS的活性(P<0.05),而蒺藜皂苷150 mg/kg和450 mg/kg治疗组均可显著降低NO含量和NOS、iNOS的活性(P<0.01).结论 侧脑室注射Aβ25～35可引起小鼠学习记忆障碍,而蒺藜皂苷可能通过抑制iNOS/NO参与的在体条件下对Aβ25～35神经毒性的介导,改善Aβ25～35致小鼠学习记忆障碍.     

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.     

大黄酚对β-淀粉样蛋白25～35致小鼠学习记忆障碍的改善作用

μl可引起小鼠学习记忆障碍,同时使脑组织NO含量增加和NOS、iNOS活性升高(P<0.01);而大黄酚(0.1,1.0,10.0 mg/kg,ip,17 d)可不同程度改善Aβ25～35造成的学习记忆障碍,并降低脑组织NO含量及NOS、iNOS活性(P<0.01).结论 侧脑室注射Aβ25～35可引起小鼠学习记忆障碍,而大黄酚可能通过抑制iNOS/NO参与的在体条件下对Aβ25～35神经毒性的介导,改善Aβ25～35致小鼠学习记忆障碍.     

不同浓度五味子水提液对训练和炎症大鼠镇痛的作用

目的比较灌胃不同浓度的五味子水提液对训练和炎症痛大鼠的镇痛作用。方法用5.2和10.4 mg/ml浓度的五味子水提液为训练和炎症痛大鼠分别灌胃,通过热板和压力测试,观察不同的时间点上对伤害性热刺激和机械刺激引起的后爪缩爪反应潜伏期(HWL),比较二者在30 min时的镇痛效果。结果当灌胃浓度为5.2 mg/ml五味子水提液时,与炎症组相比,训练组左爪热板的镇痛效果有差异(P0.05);当灌胃浓度为10.4 mg/ml五味子水提液时,训练与神经痛大鼠相比,右爪热板镇痛效果差异显著(P0.01),同时左爪压板的镇痛效果也有差异(P0.05);表明炎症痛大鼠的镇痛效果弱于训练大鼠。结论相同浓度的五味子水提液对训练大鼠的镇痛作用强于炎症痛大鼠。     

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。     

电针预处理对福尔马林致痛大鼠行为学及脊髓后角NOS表达的影响

目的探讨重复电针顸处理对福尔马林致痛大鼠行为学及脊髓后角一氧化氮合酶(NOS)表达影响的可能机制.方法采用行为学观察和NADPH-d组织化学方法相结合,观察大鼠一侧足底注射5%福尔马林50μL后,病灶所属脊髓节段(L4～L5)NOS阳性反应.结果福尔马林组注射侧脊髓背角浅层的NOS免疫活性增高,对照侧脊髓NOS阳性反应与生理盐水组和电针组的对照侧比较有统计学意义;电针可以显著抑制疼痛的Ⅱ时相反应,电针组脊髓背角NOS阳性反应较FOR组免疫活性显著减弱.结论电针可起镇痛效应,其作用机制可能是抑制NO合成,影响了脊髓神经元放电,阻遏伤害性疼痛信息向中枢传递;镇痛效应应该是脑内和脊髓共同作用的结果.     

蒺藜皂苷对老年痴呆小鼠脑组织中H2O2、CAT、GSH-Px含量及海马超微结构的影响

目的 研究蒺藜皂苷对凝聚态β-淀粉样肽(Aβ25～35)致衰老小鼠脑组织中过氧化氢(H2O2)、过氧化氢酶(CAT)、谷胱甘肽过氧化氢酶(GSH-Px)含量及海马超微结构的影响.方法 采用一次性小鼠右侧脑室注射Aβ25～35 3 μl造成AD小鼠模型,并于侧脑室注射后14 d测定各组小鼠脑组织中H2O2的含量、CAT、GSH-Px的活力并于光镜、电镜下观察小鼠大脑皮质及海马组织超微结构.结果 侧脑室注射Aβ25～35 3 μl后可引起小鼠脑组织内H2O2含量增加,同时使小鼠脑组织内CAT和GSH-Px活力显著降低,而连续蒺藜皂苷14 d治疗后,与模型组相比蒺藜皂苷150 mg/kg治疗组可显著降低H2O2含量、提高CAT和GSH-Px活性(P<0.05),蒺藜皂苷450 mg/kg治疗组可显著降低H2O2含量、提高CAT和GSH-Px的活性(P<0.01);光镜下观察结果显示正常对照组海马CA1区神经元密集、神经元结构正常;模型组神经元间隙加大,说明有轻度水肿,部分神经元核、质界限模糊,细胞嗜酸性增强;电镜下观察结果显示正常对照组神经元、神经纤维超微结构正常;模型组神经元轻度水肿,脂褐素样包含物增多,线粒体减少或消失;蒺藜皂苷各治疗组可不同程度的减轻上述病理学改变.结论 侧脑室注射Aβ25～35可引起小鼠大脑自由基增加,海马超微结构改变,蒺藜皂苷能明显改善衰老小鼠大脑组织的超微结构并呈剂量效应关系.     

朱砂莲提取物镇痛作用的实验研究

目的 观察朱砂莲提取物的镇痛作用.方法 昆明小鼠50只,随机分为对照组、哌替啶组、朱砂莲醇提取物低剂量组(ZhSL-L)、中剂量组(ZhSL-M)、高剂量组(ZhSL-H),每组10只.将所有小鼠置于恒温(55±0.5)℃热板上,以小鼠接触热板至出现舔后足的时间(s)作为痛阈指标.同时哌替啶组(0.05 g/kg)、ZhSL-L(0.2 g/kg)、ZhSL-M(0.4 g/kg)、ZhSL-H(0.8 g/kg)按相应剂量灌胃给药1次,对照组给予生理盐水0.1 ml/10g.应用热板法观察朱砂莲提取物对小鼠疼痛的镇痛作用.结果 与对照组比较,朱砂莲提取物各组均能明显延长小鼠痛阈,中、高剂量组尤为明显;与哌替啶组比较,朱砂莲提取物镇痛作用弱但维持时间长.结论 朱砂莲提取物能明显延长痛阈,且镇痛作用维持时间较长.     

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.     

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.     

β-Endorphin Antagonizes the Effects of α-MSH on Food Intake and Body Weight

Proopiomelanocortin (POMC) is posttranslationally processed to several peptides including α-MSH, a primary regulator of energy balance that inhibits food intake and stimulates energy expenditure. However, another POMC-derived peptide, β-endorphin (β-EP), has been shown to stimulate food intake. In this study we examined the effects of intracerebroventricular (icv) β-EP on food intake and its ability to antagonize the negative effects of α-MSH on energy balance in male rats. A single icv injection of β-EP stimulated food intake over a 2- to 6-h period during both the light and dark cycles. This effect was, however, not sustained with chronic icv β-EP infusion. In the next study, a subthreshold dose of β-EP was injected together with Nle(4), d-Phe(7) (NDP)-MSH after a 16-h fast, and the negative effects of NDP-MSH on refeeding and body weight gain were partially reversed. Finally, peptide interactions were studied in a chronic icv infusion model. Weight gain and food intake were significantly suppressed in the NDP-MSH group during the entire study. A subthreshold dose of β-EP antagonized these suppressive effects on food intake and weight gain for the first 3 d. However on d 4-7, β-EP no longer blocked these effects. Of note, the stimulatory effect of β-EP on feeding and its ability to antagonize MSH were specific for β-EP(1-31) and were not observed with β-EP(1-27). This study highlights the importance of understanding how the balance between α-MSH and β-EP is maintained and the potential role of differential POMC processing in regulating energy balance.     

补骨脂与双氢青蒿素合剂治疗小鼠隐孢子虫病的实验研究

用补骨脂和双氢青蒿素合剂治疗经地塞米松诱导的隐孢子虫病小鼠, 剂量为补骨脂3.4 g/kg, 双氢青蒿素60 mg/(kg·d), 灌胃, 连用7 d。 结果粪检隐孢子虫卵囊数、 全血CD4⁺、 CD3⁺ T细胞比例、 血清γ干扰素 (IFN-γ) 浓度, 以及小肠组织匀浆一氧化氮 (NO) 浓度均高于感染对照组 (P值均＜0.01)。小肠组织病变程度均轻于感染对照组。表明补骨脂和双氢青蒿素合剂可通过调节血清IFN-γ、 全血CD4⁺、 CD3⁺ T 细胞比例, 以及提高肠组织NO浓度, 参与宿主免疫应答和炎症反应过程, 抑杀虫体、 治疗小鼠隐孢子虫病。     

Analgesic and anti-inflammatory activities of Piper nigrum L.

ObjectiveTo evaluate and compare the analgesic and anti-inflammatory activity of pure compound, piperine along with hexane and ethanol extracts of Piper nigrum L. fruit in mice and rats.MethodsThe analgesic activity was determined by tail immersion method, analgesy-meter, hot plate and acetic acid induced writhing test. While the anti-inflammatory activity was evaluated by carrageenan-induced paw inflammation in rats.ResultsPiperine at a dose of 5 mg/kg and ethanol extract at a dose of 15 mg/kg after 120 min and hexane extract at a dose of 10 mg/kg after 60 min exhibited significant (P<0.05) analgesic activity by tail immersion method, in comparison to ethanol extract at a dose of 10 mg/kg using analgesy-meter in rats. However, with hotplate method, piperine produced significant (P<0.05) analgesic activity at lower doses (5 and 10 mg/kg) after 120 min. A similar analgesic activity was noted with hexane extract at 15 mg/kg. However, in writhing test, ethanol extract significantly (P<0.05) stopped the number of writhes at a dose of 15 mg/kg, while piperine at a dose of 10 mg/kg completely terminated the writhes in mice. In the evaluation of anti-inflammatory effect using plethysmometer, piperine at doses of 10 and 15 mg/kg started producing anti-inflammatory effect after 30 min, which lasted till 60 min, whereas hexane and ethanol extracts also produced a similar activity at a slightly low dose (10 mg/kg) but lasted for 120 min.ConclusionsIt is concluded from the present study that Piper nigrum L possesses potent analgesic and anti-inflammatory activities.     

Analgesic and anti-inflammatory effects of honey: the involvement of autonomic receptors

The use of honey for therapeutic purposes is on the increase and many studies have shown that honey has the ability to influence biological systems including pain transmission. Therefore, this study was designed to investigate the analgesic and anti-inflammatory effects of honey and the effects of concurrent administration of autonomic nervous system blocking drugs. Studies on analgesic activities was carried out using hotplate and formalin-induced paw licking models while the anti-inflammatory activity was by the carrageenan paw oedema method. Animals were distributed into six groups consisting of five animals each. They were administered saline, honey (600 mg/kg), indomethacin (5 mg/kg), autonomic blockers (3 μg/kg of tamsulosin, 20 mg/kg (intraperitoneally) of propranolol, 2 ml/kg of atropine or 10 mg/kg (intra muscularly) of hexamethonium) or honey (200 and 600 mg/kg) with one of the blockers. The results showed that honey reduced pain perception especially inflammatory pain and the administration of tamsulosin and propranolol spared the effect of honey. Hexamethonium also spared the effects of honey at the early and late phases of the test while atropine only inhibited the early phase of the test. However, atropine and hexamethonium spared the anti-inflammatory effects of honey but tamsulosin abolished the effects while propranolol only abolished the anti-inflammatory effects at the peak of the inflammation. The results suggest the involvement of autonomic receptors in the anti-nociceptive and anti-inflammatory effects of honey although the level of involvement depends on the different types of the receptors.     

Prenatal Exposure to Ethanol Alters the Ontogeny of the β-Endorphin Response to Stress

To determine whether prenatal exposure to ethanol alters the response of the β-endorphin (β-EP) system to stress, the effect of two types of stressful stimuli, ether and cold, was examined in the offspring of rats which during pregnancy were: (a) fed with an ethanol-containing diet; (b) pair-fed with an isocaloric sucrose diet; and (c) fed ad libitum with standard lab chow (basic control group). The effect of stress on the content of β-EP in the serum, pituitary gland and hypothalamus, as well as on the serum corticosterone and hypothalamic corticotropin-releasing factor (CRF) content was examined. Pups prenatally exposed to ethanol had significantly higher serum β-EP levels on Day 1 and higher serum corticosterone levels on Days 1-3 when compared to their pair-fed or basic controls. On all days tested pituitary β-EP content was lower in the offspring of the ethanol-treated rats than in the control groups. There was no difference in the total hypothalamic β-EP content between the three treatment groups; however, during the first 10 days of life a higher concentration (ng/mg protein) of β-EP was observed in the hypo-thalami of the ethanol and the pair-fed group when compared to the basic control pups. Hypothalamic CRF levels, though significantly lower in the pups exposed to ethanol in utero than in the control groups on Day 3, increased significantly in the ethanol group between Days 14 and 22, while no significant change was observed during this period in either of the control groups. From Days 1 to 10 significant elevations in serum corticosterone, levels were observed following both types of stress in the pair-fed and the basic control group, while no significant response, to either type of stressful stimuli, was observed prior to Day 14 in the pups exposed to ethanol prenatally. On Day 14 cold stress induced small increases in the serum β-EP and corticosterone levels of the offspring treated prenatally with ethanol which, however, were less pronounced than the elevations observed in both of the control groups. Furthermore, exposure to ether stress on Day 14 elicited no response by the β-EP system of the ethanol-exposed offspring. In contrast, the 22-day-old offspring of the ethanol-treated rats exhibited greater elevations in serum β-EP and corticosterone levels, following stress, than the offspring of the pair-fed and basic control groups. The elevations of serum β-EP levels following stress were associated with small decreases in the pituitary β-EP and hypothalamic CRF contents. Thus, the response of the β-EP system to stress was modified by prenatal exposure to ethanol, being suppressed at early postnatal life and enhanced at later stages of development. The transition from reduced to enhanced responsiveness seemed to occur during the third week of life.     

低浓度乙醇对大鼠血管内皮损伤的保护作用

目的研究低浓度乙醇对低密度脂蛋白(LDL)诱导的血管内皮损伤的保护作用与内源性一氧化氮合酶抑制物的关系。方法SD大鼠在乙醚麻醉下,舌下静脉注射人血清LDL(4mg/kg)诱发血管内皮功能损伤。检测血中非对称性二甲基精氨酸(ADMA)、丙二醛(MDA)和一氧化氮(NO)的含量,并观察离体胸主动脉环的内皮依赖性舒张反应。结果单次静注LDL(4mg/kg)显著抑制乙酰胆碱(ACh)诱导的内皮依赖性舒张,增加血液中ADMA和MDA,降低NO水平。低浓度乙醇(10%,4ml/kg)能显著减轻LDL所致ACh诱导内皮依赖性舒张的损伤,能显著抑制ADMA和MDA浓度升高,降低NO浓度。但其他浓度乙醇(5%、15%,4ml/kg)对ADMA和NO浓度有较小的影响。结论低浓度乙醇对LDL诱导的血管内皮细胞损伤有保护作用,其保护作用与降低ADMA浓度有关。     

The effect of N-nitro-L-arginine methyl ester on morphine-induced changes in the plasma corticosterone and testosterone levels in mice.

Effects of the nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg i.p.), on morphine-induced changes in the plasma corticosterone and testosterone levels were studied in male mice. Acute morphine administration (15 and 30 mg/kg i.p.) enhanced the corticosterone level after 1 and 2 hr (at a dose of 30 mg/kg only). A 4-day treatment with increasing doses of morphine, from 15 to 50 mg/kg i.p., increased the plasma corticosterone concentration at 2 hr after the last injection. Single administration of L-NAME (30 mg/kg i.p.) had no effect on the corticosterone level, whereas its repeated injections (30 mg/kg i.p., twice a day for four days) elevated the hormone concentration at 2 hr after the last dose. Pretreatment of mice with L-NAME enhanced the stimulatory effects of both acute and repeated morphine administration on the corticosterone level. D-NAME (30 mg/kg i.p.), an inactive form of the nitric oxide synthase inhibitor, had no effect on the morphine-induced changes in the corticosterone level. Acute morphine administration had no effect on the plasma testosterone level after 1 or 2 hr, whereas repeated drug injections decreased the hormone concentration after 2 hr. Single or repeated L-NAME administration did not influence the testosterone level in either control or morphine-treated animals. The above results indicate that inhibition of nitric oxide synthase enhances the stimulatory effect of morphine on corticosterone secretion, but does not influence the inhibitory effect of repeated morphine on the plasma testosterone concentration in mice.     

Melatonin decreases nitric oxide production and lipid peroxidation and increases interleukin-1 beta in the brain of mice infected by the Venezuelan equine encephalomyelitis virus

Melatonin, a potent antioxidant, has shown to be beneficial in murine Venezuelan equine encephalomyelitis (VEE) virus infection. In addition, melatonin can induces the production of interleukin-1 beta (IL-1beta), a cytokine capable of inducing increased expression of inducible nitric oxide synthase; the activity of this enzyme is increased in the brain of mice infected with VEE virus. The aim of this study was to determine the effect of VEE virus on the nitric oxide (NO) production, lipid peroxidation and IL-1beta production in the brain and serum of mice infected with VEE virus, and to investigate the modulatory role of melatonin during this viral infection. Mice were infected with 10 LD(50) of VEE virus and treated with melatonin (500 microg/kg of body weight) starting 3 days before and continuing for 5 days after virus inoculation. Mice were sacrificed on days 1, 3 and 5 postinfection and brains and blood samples were obtained. NO and IL-1beta production and lipid peroxidation levels were measured in perfused brain homogenates and serum. Increased production of brain nitrite was found on days 1, 3 and 5 postinfection and lipid peroxidation products were increased at day 5. Levels of serum nitrite were found elevated on days 3 and 5 postinfection; however, lipid peroxidation products remained similar to basal levels. Melatonin treatment decreased nitrite concentration in brain and serum of infected mice as well as the lipid peroxidation products in the brain. IL-1beta was found to be increased in the brain and serum of infected animals, and melatonin treatment induced higher levels of this cytokine (brain: about 4-fold; serum: about 8-fold). These results may be related to the beneficial effect of melatonin in the VEE experimental disease and address the possible therapeutic potential of the indoleamine in human VEE virus infection.