多萜醇体内代谢及其生物活性研究进展

多萜醇(dolichol)是一类广泛分布于自然界,存在于细菌、真菌、植物和哺乳动物体内的线状异戊烯聚合物。国外对多萜醇与聚戊烯醇(polyprenoid)及其衍生物的研究已有40多年,发现其具有抑制肿瘤、抗病毒、降血糖、护肝、造血等功能。聚戊烯醇及其衍生物在一些国家已经被作为药物应用于临床。现对多萜醇类物质的结构、分布、代谢、生物活性和临床应用进行综述。     

银杏叶聚戊烯醇联合60Co放疗Heps荷瘤鼠的药效研究

从银杏叶中分离聚戊烯醇有效部位，选择肝癌实体型(Heps)，以5，10和20mg/kg不同剂量的聚戊烯醇，分别联合^60Co放疗Heps荷瘤鼠，并与^60Co单独放疗Heps进行对比，分析抑瘤效果。结果：5，10和20mg/kg的聚戊烯醇，分别联合^60Co放疗Heps荷瘤鼠，对Heps的抑瘤率分别为67.33％，60.96％和57.69％，都明显高于^60Co单独放疗Heps的抑瘤率(54.58％)，尤其低剂量的聚戊烯醇联合^60Co放疗效果最好。结论：银杏叶聚戊烯醇联合^60Co放疗Heps荷瘤鼠，可明显提高^60Co单独放疗Heps的抑瘤效果。     

植物聚戊烯醇研究概述

聚戊烯醇（polyprenols）是由异戊烯基组成的一类类脂化合物，广泛存在于高等植物和微生物中，不同植物中聚戊烯醇含量不同。植物中聚戊烯醇主要分为三种类型，Rowland最早在1950年代从烟草中分离得到茄尼醇（solanesol），Lindgren等在1960年代从桦树和微生物中分离得到桦木醇（betulaprenol），Wellburn等从印度胶树中分离得到菲卡醇（ficaprenol）。     

正交设计法在银杏叶聚戊烯醇提取工艺中的应用

目的从银杏叶中提取聚戊烯醇同系物并对其提取工艺进行优化。方法用正交试验法以聚戊烯醇得率为指标对提取工艺进行优化,经硅胶柱色谱纯化,用高效液相色谱法(HPLC)测定聚戊烯醇含量。结果银杏聚戊烯醇提取工艺的最佳条件为以用7倍体积石油醚索氏提取10 h。结论优选出银杏聚戊烯醇提取工艺,验证试验符合要求。     

银杏叶聚戊烯醇联合化疗药对Heps和EC荷瘤小鼠的抗癌作用

目的研究聚戊烯醇联合化疗药对Heps和EC荷瘤小鼠的药效作用。方法从银杏叶中分离纯化聚戊烯醇 ,分别与氟脲嘧啶 (5 Fu)、环磷酰胺 (CTX)和顺铂 (PDD)联合应用 ,对移植性Heps和EC荷瘤小鼠进行抑瘤实验 ,并与 5 Fu、CTX和PDD单独用药比较。结果聚戊烯醇分别与CTX、PDD合用 ,对肝癌Heps的抑瘤率分别从4 2 .2 5 %、4 5 .0 4 %提高到 5 6 .4 9%、5 4 .96 % ;聚戊烯醇分别联合CTX、5 Fu用药 ,对艾氏腹水瘤EC的抑瘤率分别从37.6 4 %、39.89%提高到 6 2 .92 %、5 3.37%。结论聚戊烯醇对抗肿瘤药具有明显的辅助治疗和减毒增效的作用     

银杏叶聚戊烯醇抗癌作用的初步研究

目的 :研究银杏叶 (FoliumGinkgo)提取物—聚戊烯醇 (PolyprenolsGP 1 )的抗肿瘤作用。方法 :采用动物抗移植性肿瘤实验方法。结果 :1 0 0mg/kg的聚戊烯醇对移植性肝癌Heps和肉瘤S1 80 的实验抑制率分别为 49 1 3 %和 46 53% ,40 0mg/kg的聚戊烯醇对艾氏癌EC抑制率为 49 65 % (P <0 0 1 )。银杏叶聚戊烯醇对艾氏腹水癌EAC小鼠无明显延长寿命作用。结论 :银杏叶聚戊烯醇有良好的抗肿瘤作用 ,应进行深入研究     

银杏叶聚戊烯醇抗癌作用的初步研究

目的:研究银杏叶(Folium Ginkgo)提取物—聚戊烯醇(Polyprenols GP-1)的抗肿瘤作用。方法:采用动物抗移植性肿瘤实验方法。结果:10.0mg/kg的聚戊烯醇对移植性肝癌Heps和肉瘤S₁₈₀的实验抑制率分别为49.13%和46.53%,40.0mg/kg的聚戊烯醇对艾氏癌EC抑制率为49.65%(P<0.01)。银杏叶聚戊烯醇对艾氏腹水癌EAC小鼠无明显延长寿命作用。结论:银杏叶聚戊烯醇有良好的抗肿瘤作用,应进行深入研究。     

马尾松针叶聚戊烯醇对CCl4致大鼠急性肝损伤的保护作用

目的观察马尾松针叶聚戊烯醇对CCl4所致大鼠急性肝损伤的保护作用。方法将SD大鼠随机均分为正常对照组、模型组、联苯双酯组(50 mg·kg-1)及聚戊烯醇低、中、高剂量组(10、20、40 mg·kg-1),连续7 d ig给予相应的药物后,ip含60%CCl4的橄榄油溶液,建立大鼠急性肝损伤模型,测定血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)的水平,在光镜下观察肝脏组织的病理学变化。结果马尾松针叶聚戊烯醇20、40 mg·kg-1剂量组能明显抑制急性肝损伤大鼠ALT、AST活性的升高,减轻CCl4引起的肝脏组织病理损伤。结论马尾松针叶聚戊烯醇对CCl4致大鼠急性肝损伤具有一定的保护作用。     

Protective effect of polyprenols from pine needles of Pinus massoniana on CCl4 - induced acute liver injury in rats

目的 观察马尾松针叶聚戊烯醇对CCl4所致大鼠急性肝损伤的保护作用.方法 将SD大鼠随机均分为正常对照组、模型组、联苯双酯组(50 mg·kg-1)及聚戊烯醇低、中、高剂量组(10、20、40 mg· kg-1),连续7 dig给予相应的药物后,ip含60％CCl4的橄榄油溶液,建立大鼠急性肝损伤模型,测定血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)的水平,在光镜下观察肝脏组织的病理学变化.结果 马尾松针叶聚戊烯醇20、40 mg· kg-1剂量组能明显抑制急性肝损伤大鼠ALT、AST活性的升高,减轻CC14引起的肝脏组织病理损伤.结论 马尾松针叶聚戊烯醇对CCl4致大鼠急性肝损伤具有一定的保护作用.     

马尾松针叶聚戊烯醇对阿尔茨海默病模型小鼠学习记忆的影响

目的:观察马尾松针叶聚戊烯醇对阿尔茨海默病(AD)模型小鼠学习记忆能力的影响。方法:将140只小鼠随机分为正常对照组、假手术组、AD模型组、石杉碱甲组(0.3 mg.kg-1)、聚戊烯醇低、中、高剂量组(20,408,0 mg.kg-1),灌胃给药14 d后,一次性右侧侧脑室注射聚集态β-淀粉样蛋白(Aβ1～42)5μg制备AD小鼠模型,继续给药7 d后,通过避暗实验和Morris水迷宫实验测定AD小鼠学习记忆能力。结果:马尾松针叶聚戊烯醇408,0 mg.kg-1剂量组能明显提高AD小鼠被动回避记忆能力和空间学习记忆能力(P<0.05或0.01),且高剂量针叶聚戊烯醇(80 mg.kg-1)与0.3 mg.kg-1石杉碱甲的效果相似。结论:马尾松针叶聚戊烯醇能明显改善AD小鼠学习记忆的能力,提示马尾松针叶聚戊烯醇对AD小鼠具有一定的防治作用。     

Polyprenols isolated from Picea abies L.spruce needles influence atorvastatin-mediated muscle strength weakness in Wistar female rats

OBJECTIVE To assess the effects of polyprenols(isolated from Picea abies L.spruce needles)on muscle strength/tone and coordination,and to investigate whether polyprenols may protect atorvastatin-mediated muscle strength/tone weakness in female Wistar rats.METHODS Polyprenols at doses of 1,10 and 20mg·kg-1,atorvastatin 80mg·kg-1 or their combination were administered once daily per os for 16 consecutive days in Wistar female rats(n=9-10 per group).Assessment of muscle strength was performed by grip strength test(on day 15)and wire hang test(on day 16).Rotarod test was used to measured locomotor coordination and muscle tone(on day 16).General locomotor activity was evaluated in open field test(on day 15).Assessment of plasma cholesterol level and creatine kinase activity was done on day 17.RESULTS Atorvastatin-treated rats exhibited a marked decrease in grasping strength and hanging time.PP(20mg·kg-1)significantly protected against atorvastatin-induced muscle weakness in grip strength test,and restored it to control values.At all doses,polyprenols prolonged hanging time which was decreased by atorvastatin in wire hang test.Polyprenols per se at 1 and 10mg·kg-1 did not show difference compared to control group animals,while only at 20mg·kg-1 h anging time was prolonged vs.control in wire hang test.No changes between control and tested groups were observed in rotarod and open field tests.Blood cholesterol level was not changed in any of tested groups in female Wistar rats.Polyprenols(20mg·kg-1)significantly(by 25%)increased plasma creatine kinase activity but it was not affected by the combined treatment.CONCLUSION Since polyprenols acted as protectors of atorvastatin-induced muscle weakness,the combination of polyprenols with atorvastatin may be helpful for reducing muscle-related side effects in patients receiving a long-term atorvastatin therapy.     

Pharmacological effects of Abies polyprenols and carsil on alcohol-induced hepatitis

The introduction of polyprenols isolated from fir (Abies) tree in male rats weighing 170 - 180 g with alcohol-induced hepatitis favored reduction in hepatocyte cytolysis and cholestasis and led to an improvement of the protein- and glycogen-synthesizing function of liver. A clear tendency to normalization of the maintenance of total lipids, triglycerides and phospholipids and the inhibition of lipid peroxidization processes in the damaged organ was observed. The introduction of Abies polyprenols also improved the process of bile secretion and its chemical composition.     

Isolation and identification of an anti-inflammatory principle from Capparis spinosa

The homologous polyprenols cappaprenol-12 (1), cappaprenol-13 (2) and cappaprenol-14 (3) with 12, 13 and 14 isoprene units, respectively, could be isolated by preparative HPLC from alcoholic extracts of Capparis spinosa. Testing 2 for its anti-inflammatory activity an inhibition of the carrageenan-induced paw edema in rats of 44 vs. 67% for the standard oxyphenbutazone was found.     

A prototype prophylactic anti-influenza preparation in aerosol form on the basis of Abies sibirica polyprenols.

This research investigates a promising antiviral compound based on polyprenols from Siberian silver fir (Abies sibirica). The physico-chemical characteristics of a preparation developed in aerosol form and an estimation of its protective efficacy against aerosol challenge of laboratory animals are presented. It is shown that (1) by using a simple ultrasonic disperser one can obtain aerosol of three formulations studied with about 70% of its mass accumulated in the size range below 1.8 microm; (2) 40-100% of aerosol particles contain preparation for different formulations; (3) after delivering under specified schedules, the preparations as developed can protect up to 100% of mice against 5 LD(50) of influenza A/Aichi/2/68 (H3N2) virus aerosol infection. Animals inhaled twice the preparation doses (which were 100 times lower than injection ones of the same efficacy) and did not exceed 10 microg/mouse. It was shown that the mode of action of this immunomodulating preparation was nonspecific stimulation of immune cells' various activities.     

德国药房概况及对我国药房的启示

笔者通过在德国进修学习和查阅文献,并参考德国药师协会(Bundesvereinigung Deutscher Apothekerverb nde,ABDA)的调查数据,对德国药房的基本情况进行介绍.德国实行严格的医药分开,参考德国药房数量、药师密度、药师从业分布等情况,对我国药房今后的改革有一定借鉴意义。     

Toxins in anti-nociception and anti-inflammation.

The use of toxins as novel molecular probes to study the structure-function relationship of ion-channels and receptors as well as potential therapeutics in the treatment of wide variety of diseases is well documented. The high specificity and selectivity of these toxins have attracted a great deal of interest as candidates for drug development. This review highlights the involvement of the proteins and peptide toxins as well as non-proteinaceous compounds derived from both venomous and non-venomous animals, in anti-nociception and anti-inflammation. The possible mechanisms of these potential therapeutic agents and possible clinical applications in the treatment of pain and inflammation are also summarized.     

我国麻醉药品和精神药品政府管制中存在的问题及改革设想

通过分析我国麻醉药品和精神药品医疗使用不足和非法流失并存的问题,探讨目前我国政府管制中存在的经济性管制过多和社会性管制不足的现状,提出改革设想。从我国当前的监管制度入手,运用政府管制的相关理论,结合卫生统计数据和实例,展开综合分析。我国麻醉药品和精神药品政府管制的改革方向是减少直至消除经济性管制,不断加强和完善社会性管制。