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雷公藤甲素诱导胰腺癌细胞凋亡 总被引:2,自引:0,他引:2
目的:观察雷公藤甲素对胰腺癌细胞BxPC-3和PANC-1生长抑制及诱导细胞凋亡作用,探讨雷公藤甲素抗胰腺癌的机制。方法:雷公藤甲素处理BxPC-3和PANC—1细胞后,用M1rr法检测细胞的生长抑制,用流式细胞术检测细胞的凋亡率,用罗丹明123和DCFH—DA染色方法测定细胞线粒体膜跨膜电位变化和活性氧(ROS)的产生,用Western印迹检测Bcl-2、Bax蛋白表达的变化。结果:雷公藤甲素对胰腺癌细胞BxPC-3和PANC—1具有生长抑制和诱导细胞凋亡的作用,且呈时间和剂量依赖关系;处理72h后,胰腺癌细胞线粒体跨膜电位明显下降,Bax表达上调,Bcl-2表达下降。结论:雷公藤甲素能有效抑制胰腺癌细胞增殖,通过增强线粒体通透性诱导细胞凋亡。 相似文献
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采用HPLC法测定不同采收期雷公藤根、茎、叶的主要活性成分雷公藤甲素含量,掌握雷公藤甲素的动态积累。结果表明,雷公藤甲素浓度在7.75~250 μg·mL-1范围内线性关系良好(R2=0.9997),雷公藤加样回收率为99.21%,RSD值为1.578%,该方法回收率较好。雷公藤甲素的含量在不同生长期、不同部位存在一定差异,不同部位甲素含量由高到低依次为叶、根、茎,雷公藤叶片具有资源开发利用潜力。7~8月采收的雷公藤叶片甲素含量最高,11~12月雷公藤根部甲素含量达最高。雷公藤不同器官均具有较高的药用价值,研究结果为雷公藤人工采收、质量评价和资源开发提供一定的科学依据。 相似文献
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目的:观察雷公藤甲素引起急性肝损伤时肝细胞自噬的情况。方法:采用LC3-GFP质粒尾静脉高压注射的方法在体监测雷公藤甲素诱导肝细胞自噬的发生;用腺病毒双荧光载体m RFP-GFP-LC3感染体外培养的HepG2细胞,通过激光共聚焦显微镜和蛋白印记的方法检测细胞自噬流的强度。结果:小鼠腹腔注射雷公藤甲素(0.25 mg/kg和0.5 mg/kg)24小时,血清中ALT和AST水平均显著升高;肝组织病理结果显示肝细胞肿胀、空泡化及坏死;激光共聚焦显微镜下可检测到LC3-GFP质粒表达所呈现的绿色荧光;离体细胞实验结果证实雷公藤甲素可诱导肝细胞发生自噬流,且表现为一定程度的剂量、时间依赖性。结论:雷公藤甲素可引发急性肝损伤并伴随明显的细胞自噬。 相似文献
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雷公藤内生细菌的促生作用及其对雷公藤甲素生成的影响 总被引:2,自引:0,他引:2
从健康雷公藤植株体内分离得到23株内生细菌,对其有益生物学特征及对小麦萌发能力的影响进行评价,得出3株益生效果显著的内生细菌.这3株内生细菌均能产生植物生长素和铁载体,其中LG3、LJ10具有溶磷特性,LG3、LY4具有固氮功能并同时具有1-氨基环丙烷-1-羧酸脱氨酶(ACC脱氨酶)活性.经细菌16S rDNA序列鉴定及同源性分析发现,LG3、LY4属于肠杆菌属,LJ10属于泛菌属.回接试验表明,3株内生细菌不但能够促进雷公藤植株的生长,还能显著提高不同器官内雷公藤甲素的含量. 相似文献
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目的:观察雷公藤甲素诱导小鼠急性肝损伤的形态学特征,为进一步研究雷公藤甲素肝毒性的病理特点和毒理机制提供基础。方法:昆明种小鼠以雷公藤甲素LD50剂量(0.8 mg/kg)水溶液灌胃,分别于给药12 h及24 h后取肝组织,制备石蜡切片、冰冻切片,行常规HE染色、PCNA染色、TUNEL染色及光镜观察。部分肝组织经戊二醛固定、制备超薄切片,行透射电镜下观察。PCNA及TUNEL染色结果采用图像分析软件进行定量分析及统计学处理。结果:0.8 mg/kg雷公藤甲素灌胃后12 h即可诱导肝组织炎细胞浸润、结构破坏、肝细胞坏死及代偿性增生。透射电镜下可见肝细胞内细胞骨架结构异常、细胞器大量脱落、自噬体明显增多。PCNA及TUNEL染色结果表明,雷公藤甲素可诱导肝细胞出现显著的增殖及凋亡。结论:雷公藤甲素可诱导肝组织炎性反应发生,同时伴随肝细胞凋亡、坏死及代偿性增生。推测肝细胞自噬性凋亡是雷公藤甲素诱导急性肝损伤的关键病理环节。 相似文献
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自噬与凋亡被认为是细胞程序性死亡的两种重要途径,二者的交互联系对阐明药物的抗肿瘤机理有重要价值.众多的研究表明,雷公藤甲素对多种肿瘤细胞都具有显著的抑制作用.细胞凋亡与自噬可被相同的因素所诱导,p53蛋白可以同时对二者起调控作用,在自噬与凋亡的交互作用(crosstalk)中扮演着重要角色.本文以He La细胞为模型,研究雷公藤甲素诱导He La细胞发生自噬和凋亡的机制,并通过抑制p53依赖的转录,研究雷公藤甲素诱导He La细胞p53依赖的自噬和凋亡交互联系. 相似文献
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雷公藤的提取物在中国被用于治疗肾小球肾炎已经有30年的历史。雷公藤提取物的主要活性成分雷公藤内酯醇具有免疫抑制和抗炎的特性,然而,毒性作用限制了其临床应用。深入研究雷公藤内酯醇的药理机制,将有助于其临床应用和降低毒副反应。对国内外关于雷公藤内酯醇对肾脏影响的研究成果进行了综述。 相似文献
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Studying the molecular mechanisms that underlie the relationship between drugs and the side effects they produce is critical for drug discovery and drug development. Currently, however, computational methods are still unavailable to assess drug-protein interactions with the aim of globally inferring the contributions of various classes of proteins toward the etiology of side effects. In this work, we integrated data reflecting drug-side effect relationships, drug-target relationships, and protein-protein interactions to develop a novel network-based probabilistic model, SidePro, to evaluate the contributions of proteins toward the etiology of side effects. For a given side effect, the method applies an expectation---maximization algorithm and a diffusion kernel-based approach to estimate each protein’s contribution. We applied this method to a wide range of side effects and validated the results using cross-validation and records from the Side Effect Resource database. We also studied a specific side effect, nephrotoxicity, which is known to be associated with the irrational use of the Chinese herbal compound triptolide, a diterpenoid epoxide in the Thunder of God Vine, Tripterygium wilfordii Lei-Gong-Teng. Using triptolide as an example, we scored the target proteins of triptolide using our model and investigated the high-scoring proteins and their related biological processes. The results demonstrated that our model could differentiate between the potential side effect targets and therapeutic targets of triptolide. Overall, the proposed model could accurately pinpoint the molecular mechanisms of drug side effects, thus making contribution to safe and effective drug development. 相似文献
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Matthew R. Wright 《Chirality》1994,6(6):467-471
Although the implications of stereochemistry for pharmacokinetics are relatively well appreciated only recently has its influence on pharmacodynamics begun to be examined. The implications of different pharmacological interactions between enantiomers with similar and different kinetic properties are examined through the use of simulation of the pharmacological effect vs. time profile. The influences of assuming that the pharmacological effect is solely the result of the more active enantiomer are also discussed. The simulations demonstrate that the less pharmacologically active enantiomer may have a significant influence on the observed effect vs. time profile and that the assumption that all of the observed pharmacological activity arises from the more active enantiomer may lead to highly inaccurate prediction of the pharmacodynamic parameters. Finally, these observations suggest that the pharmacodynamic profiles of a drug administered as a racemate or as a “pure” formulation of the more active enantiomer may be significantly different. © 1994 Wiley-Liss, Inc. 相似文献
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绿原酸的药理学研究进展 总被引:48,自引:1,他引:48
绿原酸(chlorogenic acid,CGA)存在于多种植物之中,具有广泛的药理作用。近年来,对绿原酸的研究发展较快,目前研究表明绿原酸口服吸收率低,在血浆中主要以代谢产物的形式存在,主要经过肾脏排泄,具有抗氧化、抗肿瘤、抗菌、抗病毒、免疫调节、降糖等多种作用。对CGA的深入研究,将为我们科学制药与合理用药提供重要的理论依据。 相似文献
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Golub MS Kaufman FL Campbell MA Li LH Donald JM 《Birth defects research. Part B, Developmental and reproductive toxicology》2006,77(5):455-470
BACKGROUND: A variety of progestational agents have been used therapeutically and evaluated for adverse effects over the last 50 years. However, progesterone itself has come into use as a therapeutic agent only recently with the development of an orally bioavailable \"micronized\" preparation. METHODS: The current review examines progesterone adverse effects as identified in the larger literature on the toxicity of progestational agents and pharmacokinetics. RESULTS: Progesterone has cytoplasmic and membrane receptors in a variety of reproductive and nonreproductive tissues including the brain and is a potent inhibitor of GnRH. Limited information is available on progesterone receptors and actions in the fetus. Concern about exogenous progestagen effects on fetal reproductive tract development have led to considerable human research over the years, but this literature review demonstrates that contemporary developmental toxicology research on progesterone is lacking. CONCLUSIONS: Progesterone is a potent, multi-faceted endocrine agent with an expanding therapeutic profile and a minimal scientific database for evaluating safe use during pregnancy. 相似文献
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A. B. P. van Kuilenburg J. G. Maring A. Schalhorn C. Terborg H. Schmalenberg D. Behnke 《Nucleosides, nucleotides & nucleic acids》2013,32(6-7):692-698
5-Fluorouracil (5FU) and capecitabine are two of the most frequently prescribed chemotherapeutic drugs for the treatment of patients with cancer. Administration of test doses of 5FU to eight patients heterozygous for the IVS14+1G > A mutation and five control patients showed that the AUC and clearance were weak parameters with respect to the identification of patients with a DPD deficiency. However, highly significant differences were observed for the terminal half life of 5FU between DPD patients and controls. Thus, a DPD deficiency could be predicted from 5FU blood concentrations measured after the administration of a test dose of 5FU. 相似文献
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Lifang Guo Xingchao Geng Li Liu Yufa Miao Zhi Lin Min Yu Yan Fu Lihong Liu Bo Li Yongzhang Luo 《Journal of biochemical and molecular toxicology》2019,33(3)
Endostar, a potent endogenous antiangiogenic factor, is wildly used in clinics. However, it was easily degraded by enzymes and rapidly cleared by the kidneys. To overcome these shortcomings, PEGylated recombinant human endostatin was developed. In this study, the purity of M2ES was evaluated by silver stain and reversed‐phase high‐performance liquid chromatography. Ultraviolet spectrum was used to examine the structural of M2ES and endostar. The bioactivity and antitumor efficacy of M2ES were evaluated using an in vitro endothelial cell migration model and athymic nude mouse xenograft model of a heterogeneous lung adenocarcinoma, respectively. A preclinical study was performed to evaluate the acute toxicity and safety pharmacology in rhesus monkeys. The purity of M2ES was more than 98%; PEG modification has no effect on endostatin structure. Compared with the control group, M2ES dramatically retards endothelial cell migration and tumor growth. After intravenous (IV) infusions of M2ES at a dose level of three and 75 mg/kg in rhesus monkeys, there was no observable serious adverse event in both acute toxicity and safety pharmacology study. On the basis of the quality and bioactivity study data of M2ES and the absence of serious side effect in rhesus monkeys, M2ES was authorized to initiate a phase I clinical trial. 相似文献
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Habibeh Mashayekhi-Sardoo Amir Hooshang Mohammadpour Homa Nomani Amirhossein Sahebkar 《Journal of cellular physiology》2019,234(11):19339-19351
Diabetes mellitus (DM) and cancer are global problems carrying huge human, social, and economic impact. Type 2 diabetes (T2DM) is associated with an increased risk for a number of cancers, including breast, pancreatic, and liver cancer. Moreover, adverse drug reactions are higher in paitents with cancer with T2DM compared to cancer patients without T2DM. Cellular mechanisms of hyperglycemia and chemotherapy efficacy may be different depending upon the particular cancer type and the condition of the patient. This review evaluates the effect of DM on the pharmacokinetic, pharmacodynamic, and adverse drug reactions of commonly used anticancer drugs such as cisplatin, methotrexate, paclitaxel, doxorubicin, and adriamycin in both clinical and animal models. A literature search was conducted in scientific databases including Web of Science, PubMed, Scopus, and Google Scholar including the relevant keywords. The results of the effectiveness of anticancer therapies in patients with DM are, however, inconsistent because DM can negatively impact multiple diverse entities including nerves and vascular structures, insulin-like growth factor 1, the function of the innate immune system, drug pharmacokinetics, the expression levels of hepatic CYP450, Mdr 1b and enzymes that then lead to drug toxicity. However, in a few circumstances, DM led to attenuation of the toxicity of anticancer drugs secondary to attenuation of the energy-dependent renal uptake process. Overall, the impact of DM on patients with cancer is variable because of the diverse types of cancers and the spectrum of anticancer drugs. With respect to the evidence for cancer involvement in DM pathophysiology and the response to anticancer treatment in patients with DM, many questions still remain and further clinical trials are needed. 相似文献