苦参碱和氧化苦参碱的抑菌活性及增效作用

研究了苦参碱、氧化苦参碱对几种林木病原真菌孢子萌发和菌丝生长的抑制活性.结果表明苦参碱和氧化苦参碱对供试林木病原真菌孢子萌发均有抑制作用,其中苦参碱对杨褐斑病菌和龙竹材霉变菌抑制作用较强,致死中量EC50分别为123、272 μg/mL.氧化苦参碱对杉木猝倒病菌抑制作用最强,EC50为26μg/mL,活性比供试的75%百菌清可湿性粉剂(EC50=91μg/mL)和70%甲基托布津可湿性粉剂(EC50=283 μg/mL)的活性高.苦参碱和氧化苦参碱对供试林木病原真菌菌丝生长有抑制作用,其中苦参碱对松枯梢病菌抑制作用较强,EC50为428μg/mL;氧化苦参碱对华山松腐烂病菌的抑制作用较强,EC50为323μg/mL.以苦参碱(氧化苦参碱)与合成农药按1:5质量比混合进行林木病原真菌菌丝生长抑制增效试验,结果表明混剂的EC50均低于34 μg/mL,共毒系数明显大于100,对华山松腐烂病菌具显著增效作用,对杉木猝倒病菌具不同程度的相加或增效作用.     

苦参碱Fe（Ⅲ）化合物的合成和抗肿瘤活性

以广西主产中药广豆根的抗肿瘤活性成份苦参碱为天然活性配体,与Fe(Ⅱ)反应得到黄色的离子型苦参碱Fe(Ⅱ)化合物[H-Matrine][FeCl4],用X射线单晶衍射分析其晶体结构,并通过MTT法对苦参碱配体及其Fe(Ⅱ)化合物的体外抗肿瘤活性进行研究.体外抗肿瘤活性测试结果表明,相比于苦参碱配体,化合物对肾癌7860、肝癌BEL7404、结肠癌HCT116、结肠癌LOVO、鼻咽癌CNE1等肿瘤株的抑制活性明显增强,其中对肝癌细胞BEL7404和结肠癌细胞HCT116表现出较强的抑制活性.     

苦参碱对心血管的作用及其机制的研究进展

苦参碱作为一种广泛存在于豆科植物的天然产物,具有多方面的药理活性,对人体心血管系统具有抗心律失常、抗慢性心功能不全、抗心肌细胞纤维化,保护心肌缺血等作用.近10年来国内外研究者通过大量实验分别探讨了苦参碱对于心血管系统的药理活性及其机制,本文对苦参碱的心血管系统药理作用及其机制进行了综述性研究,研究表明苦参碱通过作用于细胞的离子通道,活性蛋白以及信号转导通路等来发挥作用.     

苦参碱对MPTP诱导帕金森多巴胺能 神经元损伤的保护作用

目的观察苦参碱在1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森(FD)小鼠中对多巴胺能神经元损伤的保护作用和机制.方法将25只C57BL雄性小鼠随机分为5组,由空白对照组(A组)、MPTP组(B组)和3种苦参碱(4,8和16 mg/kg)加MPTP治疗组(分别为C,D和E组)组成.记录攀岩测试和运动活动实验的结果.4 d后处死小鼠并进行解剖,检测超氧化物歧化酶(SOD)和谷胱甘肽(GSH)的水平,应用免疫荧光分析酪氨酸羟化酶(TH)的水平,通过蛋白质印记分析腹侧中脑核因子红细胞2相关因子2(Nrf2)的水平.结果苦参碱可以缓解PD相关联的典型行为,且随着增加苦参碱浓度,症状明显减轻.PD小鼠具有较低的SOD和GSH活性,且苦参碱部分扭转了SOD和GSH活性的变化.使用苦参碱的小鼠出现较高TH水平和TH阳性细胞的表达,Nrf2在PD小鼠中脑腹侧表达显著下降,而苦参碱能够扭转这种现象.结论通过促进在中脑腹侧抗氧化应激相关的Nrf2信号通路,苦参碱可以抑制PD多巴胺能神经元的氧化损伤.     

HPLC法同时测定苦豆子中苦参碱与氧化苦参碱

用反相高效液相色谱法分离并测定了苦豆子中苦参碱和氧化苦参碱建立了该中药中苦参碱与氧化苦参碱分离、测定的色谱方法．色谱条件：ＯＤＳ柱，甲醇－水－三乙胺（５５：４５：０．０２Ｖ／Ｖ）为流动相，紫外检测波长为２１５ｎｍ．     

苦参碱的药用价值

介绍了中草药苦参的化学成分及其所含的苦参碱和氧化苦参碱的药用价值。     

HPLC测定苦参配方颗粒中苦参碱与氧化苦参碱含量

采用高效液相色谱法,以氨基键合硅胶为填充剂,以乙腈-无水乙醇-3%磷酸溶液(80:10:10)为流动相,检测波长为220 nm,建立了一种可同时测定苦参配方颗粒中苦参碱与氧化苦参碱含量的方法。结果表明:苦参碱回归方程为Y=499.412 2X-8.070 1,R=0.999 9,线性范围为0.158～1.580μg。氧化苦参碱回归方程为Y=557.152 4X-15.568 8,R=0.999 9,线性范围为0.1 68 6～1.686 0μg。苦参配方颗粒中苦参碱和氧化苦参碱的总量的平均含量为4.60%,回收率在98%～103%之间,RSD为1.52%。     

中药诱导肝癌细胞凋亡的研究进展

通过综述近几年来关于中药诱导肝癌细胞凋亡的文献,综合分析了人参皂甙、紫杉醇、氧化砷、苦参碱等多种抗肿瘤中药以及合剂对肝癌细胞凋亡的影响,认为中药诱导肝癌细胞凋亡主要是通过影响肝癌细胞周期,抑制癌发生相关基因的表达以及端粒酶活性来达到防癌和抗癌的目的.某些中药诱导肝癌细胞凋亡的途径有可能是偏向其中某一种,而某些中药诱导凋亡也很有可能是多种途径共同作用的结果.     

氧化苦参碱抗猪血清诱导的免疫性大鼠肝纤维化作用研究

目的:研究氧化苦参碱对猪血清诱导的大鼠免疫性肝纤维化的影响.方法:采用猪血清诱导的肝纤维化模型,肝脏病理学检测天狼星红染色观察纤维化程度,ELISA检测血清中TGF-beta1和IL-10的含量.结果:氧化苦参碱可明显降低实验大鼠肝脏胶原沉积,肝脏羟脯氨酸含量相对于模型组显著下降(P0.05);与模型组相比,治疗组血清ALT和TGF-beta1的含量显著降低(P0.05),IL-10含量显著升高(P0.05).结论:苦参素可明显降低试验所用大鼠肝脏纤维化程度,对猪血清诱导的大鼠肝纤维化有良好的防护作用,对IL-10表达的影响或是其作用机制之一.     

西藏不同区域砂生槐在不同采收时间的花、茎、叶及种子中苦参碱、氧化苦参碱含量比较

目的：测定西藏不同区域产砂生槐在不同采收时间花、茎、叶及种子中的苦参碱与氧化苦参碱的含量,为其合理采收利用提供科学依据。方法：使用高效液相色谱（HPLC）：SHIMADZUC18色谱柱（150X4．6）;流动相：甲醇（0．05mol／L）-磷酸二氢钠溶液（含磷酸2ml／L）一高氯酸钠（15ml：85ml：O．5g）,检测波长为215rim,流速为0．7ml／min,柱温为室温。结果：种子中氧化苦参碱、苦参碱含量较高,最高的为日喀则七月份采种子,苦参碱含量（24．48mg／g）,氧化苦参碱含量（51．125mg／g）。结论：砂生槐花、茎、叶及种子中均合有苦参碱和氧化苦参碱,不同区域、不同采收时间其含量有差异,种子采收7月份最佳,利用叶子应在6-7月。     

人参皂甙Rh2抗肿瘤作用机制的研究

恶性肿瘤治疗至今尚无好的方法.传统化疗药因其缺乏特异性的细胞毒性作用,治疗中容易造成正常细胞的损伤,从而引起一系列的并发症.人参皂甙Rh2是人参中提取的天然活性成分,具有很高的抗肿瘤活性,而对正常细胞无毒副作用.文章从人参皂甙Rh2的抗肿瘤作用机制(抑制细胞增殖、诱导细胞凋亡、诱导分化、抑制肿瘤DNA合成、提高荷瘤机体的免疫功能和抑制肿瘤转移、抗肿瘤耐药性增强、其他化疗药物对耐药肿瘤作用)等方面进行研究.     

Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting

Cancer immunoediting, the process by which the immune system controls tumour outgrowth and shapes tumour immunogenicity, is comprised of three phases: elimination, equilibrium and escape. Although many immune components that participate in this process are known, its underlying mechanisms remain poorly defined. A central tenet of cancer immunoediting is that T-cell recognition of tumour antigens drives the immunological destruction or sculpting of a developing cancer. However, our current understanding of tumour antigens comes largely from analyses of cancers that develop in immunocompetent hosts and thus may have already been edited. Little is known about the antigens expressed in nascent tumour cells, whether they are sufficient to induce protective antitumour immune responses or whether their expression is modulated by the immune system. Here, using massively parallel sequencing, we characterize expressed mutations in highly immunogenic methylcholanthrene-induced sarcomas derived from immunodeficient Rag2(-/-) mice that phenotypically resemble nascent primary tumour cells. Using class I prediction algorithms, we identify mutant spectrin-β2 as a potential rejection antigen of the d42m1 sarcoma and validate this prediction by conventional antigen expression cloning and detection. We also demonstrate that cancer immunoediting of d42m1 occurs via a T-cell-dependent immunoselection process that promotes outgrowth of pre-existing tumour cell clones lacking highly antigenic mutant spectrin-β2 and other potential strong antigens. These results demonstrate that the strong immunogenicity of an unedited tumour can be ascribed to expression of highly antigenic mutant proteins and show that outgrowth of tumour cells that lack these strong antigens via a T-cell-dependent immunoselection process represents one mechanism of cancer immunoediting.     

2-巯基苯并噻唑衍生物类小分子抑制剂对人结直肠癌细胞SW620的生长抑制作用

拟研究2-巯基苯并噻唑衍生物类小分子抑制剂(SKLB-163)对结直肠癌细胞SW620增殖及凋亡的影响;并探讨可能的作用机制。使用流式细胞术检测药物处理后肿瘤细胞凋亡的情况;利用MTT实验检测细胞增殖情况。在裸鼠人结直肠癌细胞SW620移植瘤模型中评估药物灌胃给药时能否抑制肿瘤生长。流式细胞术和MTT表明,SKLB-163能够促进SW620细胞凋亡,且能够显著抑制SW620细胞的增殖。动物实验表明,口服灌胃给药SKLB-163(200 mg/kg)能够显著抑制裸鼠人结直肠癌细胞SW620移植模型肿瘤的生长。总之,SKLB-163具有较好的抗肿瘤活性;为进一步发展新型2-巯基苯并噻唑类抗肿瘤药物提供了依据。     

海嘧啶抗肿瘤作用机制的研究

研究了海嘧啶抗肿瘤作用的机制,观察了海嘧啶对荷瘤小鼠红细胞免疫粘附肿瘤细胞的功能以及对红细胞膜及肿瘤细胞膜上唾液酸的含量的影响.结果表明海嘧啶可以提高荷瘤小鼠抗肿瘤免疫功能,提高红细胞膜上唾液酸的含量,而使肿瘤细胞上的唾液酸含量降低.这可能其抗肿瘤作用的机制之一.     

Netrin-1 controls colorectal tumorigenesis by regulating apoptosis

The expression of the protein DCC (deleted in colorectal cancer) is lost or markedly reduced in numerous cancers and in the majority of colorectal cancers due to loss of heterozygosity in chromosome 18q, and has therefore been proposed to be a tumour suppressor. However, the rarity of mutations found in DCC, the lack of cancer predisposition of DCC mutant mice, and the presence of other tumour suppressor genes in 18q have raised doubts about the function of DCC as a tumour suppressor. Unlike classical tumour suppressors, DCC has been shown to induce apoptosis conditionally: by functioning as a dependence receptor, DCC induces apoptosis unless DCC is engaged by its ligand, netrin-1 (ref. 3). Here we show that inhibition of cell death by enforced expression of netrin-1 in mouse gastrointestinal tract leads to the spontaneous formation of hyperplastic and neoplastic lesions. Moreover, in the adenomatous polyposis coli mutant background associated with adenoma formation, enforced expression of netrin-1 engenders aggressive adenocarcinomatous malignancies. These data demonstrate that netrin-1 can promote intestinal tumour development, probably by regulating cell survival. Thus, a netrin-1 receptor or receptors function as conditional tumour suppressors.     

树突状细胞与妇科肿瘤的免疫治疗

树突状细胞(DC)是目前所知机体内功能最强的专职抗原提呈细胞,可在体内外向T细胞提呈抗原并诱发CTL反应,在抗肿瘤免疫中发挥重要作用.近年采用DC疫苗进行抗肿瘤治疗已成为当今肿瘤生物治疗领域备受关注的焦点之一.针对DC抗肿瘤机制、妇科肿瘤的免疫逃逸及在妇科肿瘤上的应用进行了研究.     

Gene expression profiling related to powdery mildew resistance in wheat with the method of suppression subtractive hybridization

“Bainong 3217 × Mardler” BC₅F₄ wheat line at the initial stage of inoculation with powdery mildew pathogen (Erysiphe graminis DC) was used to construct a suppression subtractive hybridization (SSH) cDNA library. Totally 760 ESTs were obtained through sequencing. Similarity analysis of ESTs based on BLASTn and BLASTx with the sequences in GenBank, in combination with macroarray differential screening, revealed that 199 ESTs of 65 kinds were known to be functionally disease resistance related. Based on the gene expression profiling in the present study, it is postulated that salicylic acid (SA) and MAP-related signal transduction pathways were involved in powdery mildew resistance in wheat. System acquired resistance genes were predominant in terms of kinds and quantity. With the initiation of cell defense reaction, the genes conferring anti-oxidation substances were largely expressed and thus cell protection mechanism was activated. Much evidence revealed that phenylpropanes metabolic pathway was involved in phytoalexin synthesis in wheat powdery mildew resistance. Genes conferring some enzymes of structural modification of cell walls and proteinase inhibitors inhibiting pathogen growth were also detected. The genes controlling a few proteinases (mainly cysteine proteinase) had a considerable redundancy of expression.