科博肽肠溶胶囊治疗晚期中、重度癌症疼痛疗效观察

目的 探讨科博肽肠溶胶囊对晚期癌症患者的止痛效果。方法 每6h口服科博肽肠溶胶囊280μg/次,常规剂量每天560μg,在用药过程中根据疼痛缓解程度调整剂量由280μg～420μg～560μg递增。结果 68例中、重度癌痛患者,显效41例,有效21例,无效6例,总有效率91．2％,药物最小日剂量280μg,最大日剂量为840μg,所有患者均可耐受,未见有药物依赖性。结论 科博肽肠溶胶囊作为控制中、重度癌痛的药物,其镇痛效果满意,副反应少,服用方便,安全,值得临床推广应用。     

大鼠脊髓内甲啡肽、强啡肽A-(1—13)和吗啡在镇痛中的相互加强作用

1.大景以辐射热甩尾法测痛。应用脊髓蛛网膜下腔,连续累加注射法观察药物的镇痛作用。脊髓蛛网膜下腔单独注射甲啡肽100nmol不能提高痛阈,但与吗啡或强啡肽A-(1—13)合用时,可明显加强后者的镇痛作用。 2.脊髓蛛网膜下腔单独注射强啡肽A-(—13)2.5nmol本身无镇痛作用,但与吗啡合用时,却能明显加强吗啡的镇痛作用。 3.本文对连续累加注射法的特点及三类阿片受体及其配基对痛觉的调制作用,进行了讨论。     

四味镇痛中药对内腓肽降解酶作用的实验研究

目的 :研究四味镇痛中药对内腓肽降解酶的作用。方法 :从大鼠的肾脏制备含有内腓肽降解酶的物质 ,建立内腓肽降解酶活性检测模型 ;并用此模型观察四味镇痛中药提取物对内腓肽降解酶特别是对中性内肽酶活性 (NEP2 4 .11)的抑制作用。结果 :(1)钩藤和羌活的水提物显示很强的NEP2 4 11酶抑制作用 ;(2 )无论是有机提取物还是水提物 ,延胡索和川芎对NEP2 4 11的抑制作用都弱于钩藤和羌活 ;(3)钩藤和羌活不仅是氨肽酶和中性内肽酶的双重抑制剂 ,而且是氨肽酶、中性内肽酶和血管紧张素转化酶的三重抑制剂。结论 :四味镇痛中药具有不同的镇痛机制 ,其中 ,钩藤和羌活通过抑制氨肽酶和中性内肽酶而发挥镇痛作用     

鱼皮胶原蛋白肽复方制品对小鼠免疫功能的影响

本试验旨在研究鱼皮胶原蛋白肽与壳寡糖、人参提取物、黄芪提取物、当归提取物的药物组合物(鱼皮胶原蛋白肽复方制品)对免疫功能的影响。将336只SPF级健康ICR雌性小鼠随机分为四批(N=84),分别进行细胞免疫功能、脏器/体重比值及体液免疫功能、单核-巨噬细胞功能及NK细胞活性检测。每批随机分为7组(n=12),阴性对照组、高(3.0 g/kg)、中(1.0 g/kg)、低(0.5 g/kg)剂量复方制品组和鱼皮胶原蛋白肽组,连续灌胃30天后,测定各项功能指标。结果发现,与阴性对照组相比,各剂量组小鼠的迟发变态反应、脏器/体重比值、抗体生成细胞数无显著差异(P>0.05);复方制品各剂量组小鼠的淋巴细胞增殖能力、血清溶血素水平以及单核-巨噬细胞碳廓清吞噬指数明显增强,且效果优于鱼皮胶原蛋白肽组。由此得出,鱼皮胶原蛋白肽复方制品具有较好的增强小鼠免疫力的作用。     

家兔中脑导水管周围灰质中甲七肽样免疫活性物质具有镇痛作用并参与电针镇痛

以辐射热照射家兔鼻嘴部皮肤,测定甩头反应潜伏期(ERL)作为痛阈。通过预先埋植的慢性套管向中脑导水管周围灰质(PAG)注射甲七肽降解酶抑制剂 Captopril,观察其镇痛作用以及加强电针镇痛的作用能否被特异的甲七肽抗血清所对抗。(1)单侧 PAG 注射 Captopril240 nmol 的镇痛作用可为同一部位注射甲七肽抗血清(1μl)所翻转,注入甲啡肽抗血清则无效。(2)单侧 PAG 注射 Captopril 60 nmol 有加强电针镇痛的作用。该作用可被1μl 甲七肽抗血清所完全取消,将抗血清量减少到0.1μl 则无效。以上结果说明 PAG 内的甲七肽样免疫活性物质在镇痛和电针镇痛中发挥重要作用。     

齐考诺肽——新一类治疗慢性疼痛的药物

在过去的40年里,治疗严重慢性疼痛一直没有理想的药物。随着对离子通道与疼痛的深入研究,现已研发出一个具有全新作用机制的肽类药物齐考诺肽（ziconotide）,它通过阻断N型钙离子通道而达到镇痛的目的。目前,齐考诺肽在欧美国家已上市,其对慢性疼痛镇痛的疗效和安全性得到确证。以N型钙离子通道为靶标研发新型慢性疼痛镇痛药受到药理研究者和临床工作者的广泛重视,这为无成瘾性镇痛药的研究指出了新的发展方向。简要阐述了齐考诺肽的结构、主要药理作用机制、应用现状及前景等。     

胆囊收缩素颉颃阿片源性镇痛

胆囊收缩素(CCK)作为神经肽类物质,其作用已被阐明:(1)调节饱感;(2)调制儿茶酚胺活性;(3)调节下丘脑肽类物质释放。目前还发现:在某些情况下,CCK的作用与阿片类物质的作用相反,例如:摄食、多巴胺更新速度、应激性摄食,遗传性肥胖的小鼠脑内β-内啡肽的含量增高而CCK含量减少。最近,Faris等又报道,CCK可颉颃阿片源性镇痛。用前足电击测定甩尾潜伏期的方法作为阿片源性镇痛的模型。给大鼠腹腔分别注射0.75、1.5、3.0、6.0μg/kg(体重)的八肽CCK,以注射同体积的生理盐水为对照,30分钟后,给予前足电击。结果极低剂量的CCK-8即可减弱内源性阿片类物质引起的镇痛作用。另外,用前足电击作为非条件刺激而形成条件反射的动物模型上,CCK-8也能减弱此种镇痛效果。     

大鼠侧脑室及鞘内注射孤啡肽对痛反应及电针镇痛的影响

孤啡肽（ＯＦＱ）是最近发现的一种１７肽,为阿片受体家族中一个新成员－“孤儿受体”的内源性配基。ＯＦＱ在痛觉调制中的作用与内阿片肽明显不同。本实验在大鼠电刺激甩尾测痛模型上,观察了侧脑室（ＩＣＶ）及鞘内注射（ＩＴ）ＯＦＱ对伤害性电刺激引起的痛反应及电针镇痛的影响。结果发现,大量ＩＣＶ及ＩＴ０．１μｇ（０．０５５ｎｍｏｌ）ＯＦＱ对痛觉反应无影响,而１．０μｇ（０．５５ｎｍｏｌ）的ＯＦＱ可明显降低痛阈;     

八肽胆囊收缩素对抗吗啡对丘脑束旁核痛反应神经元放电的影响

已知脑室注射硫化八肽胆囊收缩素(CCK-8)对吗啡镇痛效应(用辐射热甩尾反应的潜伏期作测痛指标)有对抗作用。本工作研究了脑室注射CCK-8对吗啡引起的大鼠丘脑两侧束旁核痛反应神经元同时电变化的影响。结果如下:(1)腹腔注射吗啡(10mg/kg)可抑制痛兴奋神经元(PEN)和加强痛抑制神经元(PIN)的电活动。(2)脑室注射CCK-8(15ng/15μl)能对抗吗啡引起PEN放电的抑制作用和PIN电活动的加强作用。无硫CCK-8对吗啡的效应没有对抗作用。(3)注射CCK-8可同时对抗吗啡对束旁核中一个PEN的抑制作用和一个PIN的加强作用。上述结果与甩尾阈测痛的结果一致,即CCK-8对吗啡引起的镇痛效应有明显的对抗作用。     

牛骨胶原低聚肽对小鼠伤口愈合作用的研究

目的：研究牛骨胶原低聚肽对正常小鼠伤口愈合的影响及探讨其可能作用机制。方法：SPF级ICR雄性小鼠240只,随机分为1个对照组和5个BCOPs剂量组（0.375、0.75、1.5、3.0、6.0g/kg·BW）。用打孔器建立皮肤打孔手术模型,术后连续灌胃16 d,并在术后第4、8、12、16 d分批处死老鼠,测量不同时间点小鼠伤口剩余面积,检测血清中基质细胞衍生因子（SDF 1α）浓度,并进行HE染色行病理组织学观察。结果：与对照组相比,牛骨胶原低聚肽组小鼠术后伤口面积明显缩小（P＜0.05）,血清SDF 1α浓度显著增加（P＜0.05）。并且同一时间点HE染色显示,牛骨胶原低聚肽组小鼠皮肤伤口上皮化水平、血管增生及纤维母细胞水平均优于对照组。结论：牛骨胶原低聚肽具有促进小鼠术后伤口愈合的作用,其机制可能与提高血清SDF 1α浓度有关。     

Comparison of physical dependence of ohmefentanyl stereoisomers in mice

Stereo-structural difference of ohmefentanyl stereoisomers on analgesic action and receptor affinity has been studied. To assess the difference of ohmefentanyl stereoisomers in physical dependence, the potency of physical dependence was quantified by estimating the ED50 value of ohmefentanyl stereoisomers in the naloxone-precipitated jumping test in mice. Morphine was used to assess the method and as a drug of comparison. The results indicate that the degree of physical dependence of morphine can been quantified by estimating the ED50 value of morphine withdrawal jumping induced by naloxone. A significant difference was observed in withdrawal jumping ED50 values among ohmefentanyl stereoisomers. Of these isomers, F9202 and F9204 had similarly potent analgesic action, but very significant difference in naloxone precipitated withdrawal response. Dependent potency index of F9204 was 618-fold weaker than that of F9202. It is concluded that a stereo-structural difference in physical dependence is found to exist among ohmefentanyl stereoisomers. Compound F9204 displayed a strong analgesic action and weak physical dependent potency.     

II - Prostaglandin hyperalgesia: The peripheral analgesic activity of morphine, enkephalins and opioid antagonists

Morphine, enkephalins, nalorphine, naloxone and pentazocine are shown to have a peripheral analgesic effect. In our modification of the Randall-Selitto test these substances were 50–100 times more potent than a standard local anaesthetic, lidocaine. At this peripheral site, naloxone did not antagonize the effect of morphine. Morphine had a marked analgesic effect on the hyperalgesia induced by PGE₂ and PGI₂, BaCl₂, Ca²⁺ ionophore A23187, isoprenaline but not on that induced by dibutyryl cyclic AMP. It was suggested that the peripheral analgesic effect of morphine is due to an inhibition of adenylate-cyclase activity.     

Antinociceptive effect of amitriptyline in mice of acute pain models

Tricyclic antidepressant drugs induce antinociceptive effect and suggest that their analgesic action could be related to the monoaminergic activity of the drugs. The analgesic activity of amitriptyline was observed in mouse models of acute pain. Mice were divided into different groups and were given amitriptyline in different doses alone and in combination with morphine. Reaction time in Hot-Plate and Tail-Flick tests was observed. Results showed that amitriptyline had antinociceptive effect in acute pain state in experimental models. Amitriptyline in combination with morphine had better analgesic effect than the morphine alone in Hot-Plate test.     

钩藤散浸膏对小鼠记忆障碍模型的影响

目的观察钩藤散浸膏的益智作用。方法小鼠随机均分为6组,3个实验组每天灌胃高、中、低剂量的钩藤散浸膏,模型对照组与正常对照组每天灌胃蒸馏水(0.2 mL/10 g),阳性对照组每天给与茴拉西坦溶液(三乐喜,0.2 g生药/kg.bw),连续给药3周后,除正常对照组外,用东莨菪碱、亚硝酸钠、40%乙醇分别复制小鼠记忆获得障碍、记忆巩固障碍、记忆再现障碍模型,用Y型迷宫法测定小鼠训练和测试成绩。结果三种模型实验组的训练、测试成绩都显著好于模型对照组(P<0.01),记忆再现障碍模型的实验组测试成绩明显高于正常对照组(P<0.01)。结论钩藤散浸膏对各模型小鼠的记忆障碍皆有明显的改善作用,说明钩藤散浸膏有一定的益智作用。     

II - Prostaglandin hyperalgesia: the peripheral analgesic activity of morphine, enkephalins and opioid antagonists.

Morphine, enkephalins, nalorphine, naloxone and pentazocine are shown to have a peripheral analgesic effect. In our modification of the Randall-Selitto test these substances were 50--100 times more potent than a standard local anaesthetic, lidocaine. At this peripheral site, naloxone did not antagonize the effect of morphine. Morphine had a marked analgesic effect on the hyperalgesia induced by PGE2 and PGI2, BaCl2, Ca2+ ionophore A23187, isoprenaline but not on that induced by dibutyryl cyclic AMP. It was suggested that the peripheral analgesic effect of morphine is due to an inhibition of adenylate-cyclase activity.     

Blockade of morphine supersensitivity by an antisense oligodeoxynucleotide targeting the delta opioid receptor (DOR-1)

An antisense oligodeoxynucleotide (ODN) targeting 20 bases of the coding sequence of the cloned delta opioid receptor (DOR-1), a mismatched ODN (different from the antisense ODN at 4 bases) or saline was administered to 3 groups of CD-1 mice implanted with naltrexone pellets (7.5 mg) for 7 days. Morphine supersensitivity (i.e., increased potency as defined by decreased morphine ED₅₀ values) was observed 24 h after pellet removal (day 8) in mice treated with saline or mismatch ODN, but not in antisense ODN treated mice. Antisense ODN alone had no effect on basal nociceptive thresholds or morphine analgesia but reduced the analgesic potency of the delta₂ opioid agonist [D-Ala²]deltorphin II. These data suggest that the delta₂ opioid receptor system participates in the adaptive changes contributing to increased morphine potency following chronic naltrexone treatment.     

Tolerance to effects of clonidine and morphine on sulfobromophthalein disposition in mice

Chronic treatment of mice with clonidine or morphine caused tolerance to the analgesic and thermoregulatory effects of these drugs. After chronic morphine, mice also became tolerant to the analgesic and thermoregulatory effects of clonidine. Cross tolerance to the hypothermic effect of morphine was demonstrated after chronic clonidine administration, but no diminution of morphine-induced analgesia could be shown. Morphine and clonidine acutely increased the retention of sulfobromophthalein (BSP) in plasma and liver. Chronic dosing with morphine or clonidine caused partial tolerance and cross-tolerance to the rise in hepatic BSP caused by an acute challenge with either agonist. However, both drugs elevated plasma BSP levels similarly in tolerant and non-tolerant mice. Thus, regimens which readily induced tolerance to the analgesic and hypothermic effects of morphine or clonidine were only partially effective in modifying the acute hepatobiliary effects of these drugs.     

L-阿拉伯糖对尿酸的调节作用

转录因子是一类在生物生命活动过程中起到调控作用的重要因子,参与了各种信号转导和调控过程,可以直接或间接结合在顺式作用元件上,实现调控目标基因转录效率的抑制或增强,从而使植物在应对逆境胁迫下做出反应。 WRKY转录因子在大多数植物体内都有分布,是一类进化非常保守的转录因子家族,参与植物生长发育以及响应逆境胁迫的生理过程。众多研究表明,WRKY转录因子在植物中能够应答各种生物胁迫,如细菌、病毒和真菌等;多种非生物胁迫,包括高温、冷害、高光和高盐等;以及在各种植物激素,包括茉莉酸( JA)、水杨酸( SA)、脱落酸( ABA)和赤霉素( GA)等,在其信号传递途径中都起着重要作用。 WRKY转录因子家族蛋白至少含有一段60个氨基酸左右的高度保守序列,被称为WRKY结构域,其中WRKYGQK多肽序列是最为保守的,因此而得名。该转录因子的WRKY结构域能与目标基因启动子中的顺式作用元件W￣box( TTGAC序列)特异结合,从而调节目标基因的表达,其调控基因表达主要受病原菌、虫咬、机械损伤、外界胁迫压力和信号分子的诱导。该文介绍了植物WRKY转录因子在植物应对冷害、干旱、高盐等非生物胁迫与病菌、虫害等生物胁迫反应中的重要调控功能,并总结了WRKY转录因子在调控这些逆境胁迫反应过程中的主要生理机制。     

III - Prostaglandin hyperalgesia: relevance of the peripheral effect for the analgesic action of opioid-antagonists

Morphine injected into the rat cerebral ventricles had a marked analgesic effect, while no effect was observed with pentazocine and naloxone or nalorphine caused a strong hyperalgesia. Administered systemically (IP) naloxone and nalorphine caused a transitory analgesia followed by a long lasting hyperalgesic effect; morphine and pentazocine showed only an analgesic effect. It was concluded that the site of analgesic action of opioid-antagonists is peripheral rather than central. The peptidase-resistant enkephalin-analog, BW 180c, which does not cross the blood brain barrier, caused a marked analgesia by IP administration to paws made hyperalgesic by PGE2 or carrageenin. It is suggested that agents derived from morphine, morphine-antagonists, enkephalins or cGMP devoid of central effect but having a strong peripheral effect may constitute a new class of safer analgesics.     

III - Prostaglandin hyperalgesia: Relevance of the peripheral effect for the analgesic action of opioid-antagonists

Morphine injected into the rat cerebral ventricles had a marked analgesic effect, while no effect was observed with pentazocine and naloxone or nalorphine caused a strong hyperalgesia. Administered systemically (IP) naloxone and nalorphine caused a transitory analgesia followed by a long lasting hyperalgesic effect; morphine and pentazocine showed only an analgesic effect. It was concluded that the site of analgesic action of opioid-antagonists is peripheral rather than central. The peptidase-resistant enkephalin-analog, BW 180c, which does not cross the blood brain barrier, caused a marked analgesia by IP administration to paws made hyperalgesic by PGE₂ or carrageenin. It is suggested that agents derived from morphine, morphine-antagonists, enkephalins or cGMP devoid of central effect but having a strong peripheral effect may constitute a new class of safer analgesics.