中药癌痛克抗炎镇痛的实验研究

目的 :研究中药抗癌痛克抗炎镇痛的作用效果。方法 :取小鼠随机分成 4组 ,每组 11～ 12只。阴性对照组给予生理盐水 30mL/kg ,阳性对照组给予消炎痛 1 2 5mg/kg ,中药大剂量组给予癌痛克2 5 0mg/kg ,中药小剂量组给予癌痛克 12 5mg/kg ,连续灌胃给药 3～ 8d ,每天 1次 ,每次 0 6 5mL ,将二甲苯涂于各组小鼠右耳致炎 ;腹腔注射 0 6 %的醋酸溶液致痛使其产生扭体反应 ;将小鼠置于YSD IX药理热板仪中 ,调节温度 5 5℃ ,观察记录小鼠在不同时间内接触热板至舔后足的时间。结果 :中药癌痛克对二甲苯致炎的小鼠耳肿胀具有明显的抑制作用 ,同时能显著抑制小鼠扭体反应的发生率和延长小鼠舔足反应的潜伏期。结论 :实验研究表明 ,中药癌痛克具有较强的抗炎镇痛作用。     

中药癌痛克抗炎镇痛的实验研究

目的：研究中药抗癌痛克抗炎镇痛的作用效果。方法：取小鼠随机分成4组，每组11－12只。阴性对照组给予生理盐水30mL/kg，阳性对照组给予消炎痛1.25mg/kg,中药大剂量组给予癌痛克250mg/kg，中药小剂量组给予癌痛克125mg/kg，连续灌胃给药3－8d，每天1次，每次0.65mL，将二甲苯涂于各组小鼠右耳致炎；腹腔注射0．6％的醋酸溶液致痛使其产生扭体反应；将小鼠置于YSD－IX药理热板仪中，调节温度55℃，观察记录小鼠在不同时间内接触反至舔后足的时间。结果：中药癌痛克对二甲苯致炎的小鼠耳肿胀具有明显的抑制作用，同时能显著抑制小鼠扭体反应的发生率和延长小鼠舔足反应的潜伏期。结论：实验研究表明，中药癌痛克具有较强的抗炎镇痛作用。     

脑瘤消胶囊镇痛和抗炎作用的药理学研究

目的观察脑瘤消胶囊对动物的镇痛和抗炎作用。方法①热板法,②扭体法,③二甲苯诱发小鼠耳廓肿胀法,④卵蛋白诱发大鼠足跖肿胀法,研究脑瘤消胶囊的抗炎止痛作用。结果0.5～2.0g/kg脑瘤消胶囊(每克药粉相当生药量13.69g)灌胃给药可①抑制热刺激和化学刺激引起的疼痛反应;②减轻二甲苯引起的小鼠耳廓肿胀;③减轻卵蛋白引起的大鼠后足跖肿胀。结论脑瘤消胶囊具有一定的抗炎止痛作用。     

脑瘤消胶囊镇痛和抗炎作用的药理学研究

目的 观察脑瘤消胶囊对动物的镇痛和抗炎作用。方法 （1）热板法,（2）扭体法,（3）二甲苯诱发小鼠耳廓肿胀法,（4）卵蛋白诱发大鼠足跖肿胀法,研究脑瘤消胶囊的抗炎止痛作用。结果 0.5-2.0g/kg脑瘤消胶囊（每克药粉相当生药量13.69g)灌胃给药可;（1）抑制热刺激和化学刺激引起的疼痛反应;（2）减轻二甲苯引起的小鼠耳廓肿长;（3）减轻卵蛋白引起的大鼠后足跖肿胀。结合 脑瘤消胶囊具有一定的抗炎止痛作用。     

β—榄香烯对小鼠脑内接种G422模型的治疗及镇痛作用的研究

目的 观察β-榄香烯水剂对小鼠脑内接种神经胶质瘤（G422）的治疗作用及β-榄香烯乳剂的镇痛作用。方法 小鼠脑内接种神经胶质瘤,分别腹腔注射β-榄香烯水剂及乳剂，观察荷脑瘤小鼠生命周期；以热板法观察β-榄香烯乳剂对小鼠的镇痛作用。结果 β-榄香烯水剂80、60、40mg/kg能延长荷脑瘤小鼠的生命周期，延长率依次为24．0％、37．0％、36．0％及22．0％；β-榄香烯乳剂20、15、及10mg/kg能显著提高小鼠的痛阈。结论 β-榄香烯能延长小鼠的生命周期，具有抗G422脑瘤的作用。能显著提高小鼠的痛阈，具有镇痛作用。     

化坚拔毒膜对内脏疼痛模型大鼠的镇痛作用及其机理探讨

目的:观察化坚拔毒膜对内脏疼痛模型大鼠的镇痛作用及对脑内单胺类神经递质含量的影响.方法:在大鼠腹部涂抹不同剂量的化坚拔毒膜后,腹腔注射冰醋酸致痛造模,观察各组大鼠对疼痛的扭体反应;用高效液相-电化学法检测脑内5-羟色胺(5-HT)、多巴胺(DA)、去甲肾上腺素(NE)含量. 结果:化坚拔毒膜各剂量组对大鼠扭体反应均有显著的抑制作用;能明显提高大鼠脑内5-HT含量,降低NE的含量,对DA影响不大.结论: 化坚拔毒膜对内脏疼痛模型大鼠有明显的镇痛作用,其镇痛机制可能与调整脑内单胺类神经递质含量密切相关.     

东莨菪亭和橙皮素联用的镇痛效果定量分析

目的：应用均匀设计法,定量分析海滩牵牛中东莨菪亭和橙皮素联用对冰醋酸所致小鼠扭体实验的镇痛效果。方法：设置5个水平的东莨菪亭（S）和橙皮素（H）联用比例和剂量,采用冰醋酸致小鼠扭体模型,观察不同组合的镇痛效果,综合数理分析结果,确定最优配方。结果：联合使用橙皮素194.5mg/kg和东莨菪亭15.36mg/kg对冰醋酸所致小鼠扭体实验可达到最佳的抑制作用。最佳剂量范围,H：175～215mg/kg;S：14～17mg/kg。结论：本实验采用均匀设计法确定了海滩牵牛中东莨菪亭和橙皮素联用对冰醋酸所致小鼠扭体实验的镇痛效果的最佳配比。均匀设计法可用于多药物联用的定量分析,但有一定的局限,其结果需经实验确证。     

无花果提取液镇痛作用的研究

本品系桑科植物无花果(Ficus Carica L)经迴流蒸溜提取配制而成,具有镇痛作用。本研究采用热板法和化学物质刺激扭腹法,测定本品的镇痛效果。 方法与结果 热板法:将合格小鼠(许可证号:苏科采动13号)皮下接种艾氏腹水癌(EAS)、肉瘤180(S180),使成为荷瘤小鼠。8天后随机分组(每组10只,雌雄各半),并将恒温水浴调节至55±0.5℃,分别测定给     

中药癌痛克的实验研究与临床观察

[目的]研究中药癌痛克的作用机理,为临床用药提供理论依据.[方法]取小鼠44～48只,随机分成4组,每组11～12只.阴性对照组给予凉开水,阳性对照组给予西药消炎痛,实验大小剂量组给予中药癌痛克.连续灌胃给药5d、6d、30d,每天1次,每次0.65 ml.用显微视像循环测定仪测定小鼠耳廓小动脉血流变化,观察记录小鼠在15 min内的扭体反应次数,并计算扭体抑制率,用微量快速检测法测定SOD的含量.临床观察癌症疼痛病人40例,其中轻度疼痛(Ⅱ级)6例,中度疼痛(Ⅲ级)24例,重度疼痛(Ⅳ级)8例,难以忍受的剧烈疼痛(V级)2例.[结果]中药癌痛克能加快小鼠耳廓小动脉的血流速度,抑制小鼠扭体反应的发生率和提高小鼠血中SOD的活性.40例癌痛患者,完全缓解9例占22.5%;明显缓解15例占37.5%;轻度缓解7例占17.5%;无效10例占25%,总有效率为75%.[结论]中药癌痛克具有明显的活血化淤及良好的镇痛作用,同时,具有加快清除自由基的功效.对癌症疼痛病人有较好的止痛作用.     

莪术醇生物修饰构建的瘤苗治疗胃癌的实验研究

目的探讨中药莪术的提取物——莪术醇修饰构建的肿瘤细胞疫苗对SGC-7901胃癌的抗瘤效应及联合新城鸡疫病毒(NDV)疫苗的综合效应。方法对SGC-7901胃肿瘤细胞进行系列处理,用莪术醇及NDV对其进行系列生物构建,修饰构建的瘤苗经免疫小鼠(1次/周×3)21天后,接种SGC-7901胃肿瘤细胞,根据设计观察各组抑制肿瘤肺转移、皮下结节形成、生存时间状况及LAK细胞的杀伤效应。结果经莪术醇修饰构建的SGC-7901肿瘤疫苗与对照组相比能明显阻止胃癌细胞的肺转移,显著抑制皮下肿瘤结节形成,明显延长荷瘤鼠的生存时间(P<0.05);用各组免疫接种后长期存活的脾细胞制备的LAK细胞,较同龄未免疫小鼠的脾细胞制备的LAK细胞具有更强的抗瘤效应(P<0.05);由NDV构建的疫苗的抗瘤作用低于莪术醇瘤苗组,莪术醇与NDV联合构建的瘤苗其抗瘤作用未呈现生物放大及相加效应。结论莪术醇修饰构建的SGC-7901新型肿瘤疫苗可以增强胃肿瘤细胞的免疫原性,对胃癌有较好的实验治疗作用。     

Acetic acid, a potent stimulator of mouse epidermal macromolecular synthesis and hyperplasia but with weak tumor-promoting ability.

The effects of a single application of various dose levels of acetic acid or the weak tumor promoter, phorbol-12,13-ditetradecanoate, on the incorporation of tritiated thymidine (3H-TDR), 3H-cytidine, and 3H-leucine into DNA, RNA, and protein of mouse epidermis, respectively, were determined and compared with histologic changes in the skin. Treatment with either 500 or 833 mumoles acetic acid induced a sequential and sustained stimulation of RNA, protein, and DNA synthesis, which was followed by extensive epidermal hyperplasia similar to that reported for the strong promoter and irritant, 12-O-tetradecanoyl-phorbol-13-acetate. A dose-response relationship between the amount of acetic acid and the rate of DNA synthesis was found between the dose levels of 33 to 833 mumoles of acetic acid per application. The latter dose induced the maximum activation of 3H-TDR into DNA at 723% of control at 2 days, whereas 33 mumoles stimulated DNA synthesis earlier and peaked at 210% of control at 3 hours. Phorbol-12,13-ditetradecanoate also stimulated macromolecular synthesis in a similar sequence, though to a lesser degree. No observable inflammation and only a slight hyperplastic response were noted with phorbol-12,13-ditetradecanoate. Weekly applications of 667 mumoles of acetic acid produced a maximal tumor response of 0.73 papilloma/mouse after 32 weeks of promotion. However, a weekly dose of 677 mumoles of acetic acid was essentially inactive when given in two divided doses. When croton oil was administered twice weekly at a 0.25%-dose level, 10.2 papillomas/mouse were induced after 32 weeks of promotion. The results showed that the previously considered nonpromoting inflammatory agent, acetic acid, must be a weak promoter. However, there was no correlation between stimulated macromolecular synthesis or hyperplasia and tumor promotion when phorbol esters were compared with acetic acid.     

Inflammatory effects of the tumor promoter croton-oil in BALB/c mice skin

A single dose of 0.25% croton oil induced an edema when applied to the ears of BALB/c mice. The maximal edematous response resulted from a single application of 4% croton oil. At any dose level, edema maximized 6-7 h after croton oil application, waning thereafter to the control level by 30 h. When topically applied on the shaved back skin, a single dose of 0.25% croton oil induced an inflammatory effect characterized by epidermal hyperplasia and infiltration of polymorphonuclear leucocytes (PMNs) in the dermis. Higher doses of croton oil caused more remarkable inflammatory response. The histological changes which were slightly detected in the skin 4 h after application of croton oil, reached a maximal level by 20-27 h, but substantially subsided by 72 h. Results proved that the tumor-promoter croton oil induces an inflammation in mice skin in a dose- and time-dependent process.     

白藜芦醇对癌的化学预防作用

背景与目的：白藜芦醇广泛存在于药食两用植物中,其开发利用已得到越来越多的关注。本研究旨在依据癌发生、发展的多阶段理论,选用经典的动物模型,从多个靶点探讨白藜芦醇对癌的化学预防作用。方法：采用抗Ames法、抗微核法检测白藜芦醇抗突变作用。巴豆油诱发的小鼠耳肿胀和小鼠表皮组织中鸟氨酸脱羧酶的活性来判断其抗促癌作用。通过检测二甲基苯蒽／巴豆油诱发的小鼠皮肤二阶段乳头状瘤模型全面观察其对肿瘤发生的抑制作用。结果：白藜芦醇可以明显减少致癌剂诱发的鼠伤寒沙门氏菌TA100回复突变菌落数,每皿用量100μg对甲基磺酸甲酯作用的抑制率达42．2％,每皿200μg对苯并芘作用的抑制率达91．8％。提前灌喂白藜芦醇可以显著对抗环磷酰胺诱发的小鼠骨髓嗜多染红细胞微核增加,并呈现较好的剂量依赖关系。将白藜芦醇以每日30mg／kg剂量灌喂6天,能有效减轻致炎剂引起的小鼠耳部急性炎性反应。以每日180mg／kg剂量给药3天,对巴豆油激发的小鼠表皮组织鸟氨酸脱羧酶活性增高抑制率达69．3％。应用白藜芦醇可以推迟二甲基苯蒽／巴豆油诱发的小鼠皮肤乳头状瘤发生时间,降低肿瘤发生率,减少平均荷瘤数。结论：白藜芦醇在癌发生的突变、促癌及演进各阶段均可发挥积极的对抗作用。作为癌化学预防剂,具有较好的开发应用前景。     

藏茵陈总萜酮的致突变及抗突变作用

目的：研究藏茵陈总萜酮的致突变及抗突变作用。方法：致突变实验采用Ames实验及小鼠体内微核实验。Ames实验采用常规掺入法;微核实验采用连续灌胃给药10 d的骨髓嗜多染红细胞微核计数法。抗突变实验采用体内、体外两种方法,体外法选用TA100及TA102菌株与环磷酰胺(每皿200 μg)和丝裂霉素C(每皿2 μg)共孵育30 min后,分别给予藏茵陈总萜酮每皿156、312、625、1 250及2 500 μg,检测其对阳性剂诱发的已突变菌落的保护作用;体内实验采用藏茵陈总萜酮25、50及100 mg/kg小鼠连续灌胃给药10 d后,给予40 mg/kg环磷酰胺或2 mg/kg丝裂霉素C,计算微核率,检测其对未发生突变的骨髓细胞的保护作用。结果：致突变实验中,藏茵陈总萜酮在每皿< 2 500 μg剂量下,未诱发Ames实验各菌株回变菌落数增加;在每皿< 40 mg/kg剂量下,未诱发骨髓嗜多染红细胞微核率增高。抗突变实验中,藏茵陈总萜酮在每皿625~ 2 500 μg范围内,可使阳性致突变剂环磷酰胺和丝裂霉素C所诱发的高回变菌落数出现明显降低;藏茵陈总萜酮在50~ 100 mg/kg剂量范围,可使阳性剂环磷酰胺或丝裂霉素C所诱发的高微核率出现明显降低。结论：本实验条件下,藏茵陈总萜酮未表现出诱导基因突变和染色体畸变作用,且有显著的抗突变作用。     

The cellular events associated with regression and progression of murine (Moloney) sarcomas

Tumors were induced in adult and neonatal mice by intramuscular injections of either 10⁴ or 10⁶ cells from a cultured murine (Moloney) sarcoma line. Neoplasms that progressed were induced in neonates by either dose, and in adults only by the larger dose; adult mice receiving 10⁴ cells usually developed tumors that regressed. Light microscopic examinations were performed at 2–3 day intervals throughout the course of tumor development and subsequent regression or progression. Initially all tumors became infiltrated with polymorphonuclear leukocytes—mainly neutrophils—and edema was extensive. By the end of the second week post inoculation, this acute inflammatory infiltrate had been replaced in adult mice by one consisting of mononuclear cells; neonatal mice never developed significant numbers of these inflammatory cells in their tumors. Of particular significance, since mononuclear inflammatory cells were associated intimately with tumors during the process of regression, was the disappearance of these cells 12–14 days post inoculation from tumors destined to progress in adult mice. Hyperplastic changes were found in the cortices and medullae of regional lymph nodes draining both progressing and regressing sarcomas. Secondary neoplasms developed commonly, and the distribution of these lesions was related to the ages of mice at the time of inoculation.     

糖皮质激素在肿瘤周围血管源性脑水肿中的临床应用

脑肿瘤可以引起肿瘤周围水肿,水肿是血液-肿瘤屏障漏渗形成的,当大脑无法清除多余的液体时,持续水肿状态并进一步发展,是引起发病率和死亡率上升的主要原因.糖皮质激素在围术期应用的益处,包括减轻术后恶心呕吐、协调镇痛、提高病人康复治疗等,吸引了人们的目光.早在几十年以前,就已经将糖皮质激素应用于肿瘤周围脑水肿的治疗中,并取得...     

Effect of resiniferatoxin pretreatment on the inflammatory response to phorbol-12-myristate-13-acetate in mouse strains with different susceptibilities to phorbol ester tumor promotion

All tumor-promoting phorbol esters induce inflammation in mouse skin. The correlation between promoting and inflammatory activities is only partial, however, indicating that only some events in inflammation may be closely coupled to the process of tumor promotion. Resiniferatoxin (RTX), an extremely inflammatory phorbol-related diterpene, acts as an ultrapotent analog of capsaicin to stimulate and then to block the neurogenic inflammatory pathway. In CD-1 mice, we have used pretreatment with RTX to show that the erythema and edema responses to phorbol and 12-deoxyphorbol esters in significant part involve this neurogenic inflammatory pathway. We report here that mouse strains with differing sensitivities to phorbol-ester-induced promotion displayed marked differences in the effect of pretreating with RTX on the edema response following phorbol-12-myristate-13-acetate (PMA) application. In the highly promotion-sensitive SENCAR mouse, RTX pretreatment had little inhibitory effect; the edema response to PMA was similar with or without RTX pretreatment 6 h before PMA application. On the other hand, in C57BL/6J mice, which are resistant to promotion by phorbol esters under the usual protocols, the edema response to PMA was totally eliminated by RTX pretreatment during the first 8 h after PMA administration. DBA/2J mice, which are similar to CD-1 mice in their susceptibility to PMA promotion, responded similarly to CD-1: the edema response was blocked partially by RTX pretreatment during the early phase (up to 8 h) of inflammation. Our results suggest that the RTX-resistant component of PMA-induced edema may correlate better with the sensitivity to promoting action than does the overall inflammatory response.     

Alteration of strain background and a high omega‐6 fat diet induces earlier onset of pancreatic neoplasia in EL‐Kras transgenic mice

Diets containing omega‐6 (ω‐6) fat have been associated with increased tumor development in carcinogen‐induced pancreatic cancer models. However, the effects of ω‐6 fatty acids and background strain on the development of genetically‐induced pancreatic neoplasia is unknown. We assessed the effects of a diet rich in ω‐6 fat on the development of pancreatic neoplasia in elastase (EL)‐Kras^G12D (EL‐Kras) mice in two different backgrounds. EL‐Kras FVB mice were crossed to C57BL/6 (B6) mice to produce EL‐Kras FVB6 F1 (or EL‐Kras F1) and EL‐Kras B6 congenic mice. Age‐matched EL‐Kras mice from each strain were compared to one another on a standard chow. Two cohorts of EL‐Kras FVB and EL‐Kras F1 mice were fed a 23% corn oil diet and compared to age‐matched mice fed a standard chow. Pancreata were scored for incidence, frequency, and size of neoplastic lesions, and stained for the presence of mast cells to evaluate changes in the inflammatory milieu secondary to a high fat diet. EL‐Kras F1 mice had increased incidence, frequency, and size of pancreatic neoplasia compared to EL‐Kras FVB mice. The frequency and size of neoplastic lesions and the weight and pancreatic mast cell densities in EL‐Kras F1 mice were increased in mice fed a high ω‐6 fatty acid diet compared to mice fed a standard chow. We herein introduce the EL‐Kras B6 mouse model which presents with increased frequency of pancreatic neoplasia compared to EL‐Kras F1 mice. The phenotype in EL‐Kras F1 and FVB mice is promoted by a diet rich in ω‐6 fatty acid.     

Erythropoietin restores the antitumor effectiveness of photodynamic therapy in mice with chemotherapy-induced anemia.

PURPOSE: The study was designed to examine the impact of anemia on the antitumor efficacy of photodynamic therapy (PDT) in a murine colon-26 adenocarcinoma model syngeneic with BALB/c mice. EXPERIMENTAL DESIGN: Acute hemolytic anemia was induced by a single i.p. injection of phenylhydrazine hydrochloride (150 mg/kg). Anemia induced by i.p. administration of carboplatin (100 mg/kg) was corrected by s.c. treatment with recombinant human erythropoietin (1000 units/kg/day). The effectiveness of PDT (10 mg/kg Photofrin, 150 J/cm2 laser dose) was evaluated by measurements of the footpad edema and tumor volume. All of the RBC-related parameters were measured from the tail vein. RESULTS: Phenylhydrazine hydrochloride injection resulted in a blunted response of normal tissues to Photofrin-mediated PDT-induced edema formation. Similarly, the antitumor response in mice with hemolytic anemia was nearly completely abrogated. The antitumor effectiveness of PDT was also significantly diminished in a more realistic clinical situation when anemia was induced by administration of carboplatin. Importantly, administration of recombinant human erythropoietin completely restored the sensitivity of the tumor to PDT in carboplatin-treated mice. CONCLUSIONS: These results indicate that anemia can negatively influence the therapeutic effectiveness of PDT. For optimal antitumor response anemia should be corrected before PDT procedure.     

Immunomodulation of natural killer cell activity by flavone acetic acid: occurrence via induction of interferon alpha/beta

The investigational drug flavone acetic acid (FAA) systemically augments natural killer (NK) cell activity in normal and tumor-bearing mice and in human cancer patients. The results from the present investigation demonstrate that in vivo administration of FAA induces in a dose-dependent manner high levels of serum interferon (IFN) within 4 hours in BALB/c, C57BL/6, and BALB/c nude mice. Antibody neutralization studies indicated that FAA induced IFN of the alpha/beta type, while molecular hybridization studies demonstrated that FAA rapidly stimulated the production of IFN alpha mRNA in splenic leukocytes. In vivo administration of anti-IFN alpha/beta antibodies to FAA-treated mice inhibited the FAA-induced augmentation of splenic NK cell activity at 4 hours. These results suggest that FAA mediates its anti-tumor effects indirectly by immunomodulation as well as directly by antiproliferative or cytotoxic activity.