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1.
将 6月龄雌性SD大鼠随机分为假手术组 (sham)、去卵巢组 (OVX)和去卵巢 +氨基胍组 (OVX +AG)。去除双侧卵巢 2周后用氨基胍治疗 13周。禁食 2 4h ,放血处死动物 ,取血和主动脉 ,分别测定主动脉AGEs、血脂和血清过氧化物含量。结果表明 ,与假手术组比较 ,去卵巢组主动脉AGEs、甘油三脂 (TG)、氧化低密度脂蛋白 (OX LDL)、丙二醛 (MDA)均明显升高 (分别为P <0 0 1,P <0 0 5 ,P <0 0 5和P <0 0 1) ;高密度脂蛋白 胆固醇 (HDL C)、载脂蛋白AⅠ (apo AⅠ )和超氧化物歧化酶 (SOD)活性均显著降低 (均P <0 0 1)。氨基胍组与病理组比较 ,主动脉AGEs、血清TG、MDA和OX LDL均明显降低 (分别为P <0 0 1,P <0 0 5、P <0 0 5和P <0 0 1) ;HDL C、apo AⅠ和SOD活性均显著升高 (均P <0 0 1)。提示氨基胍通过降低去卵巢大鼠主动脉AGEs含量 ,降低大鼠血清OX LDL和TG水平 ,升高HDL C、apo AⅠ水平和SOD活性 ,发挥其对心血管的保护作用  相似文献   
2.
水飞蓟素对乳腺癌细胞系的作用及其机制研究   总被引:5,自引:0,他引:5  
韩月恒  韩炯  李莹  刘新平  药立波 《中草药》2003,34(3):238-241
目的:研究水飞蓟素在体外对不同乳腺癌细胞系的作用,并进一步探讨其作用机制。方法:MTT实验测定水飞蓟素对乳腺癌细胞系MCF-7和SK-BR-3的半数抑制浓度(IC50);软琼脂克隆形成试验检测加药后两种细胞在软琼脂内的增殖能力。在此基础上,用Her-2抑制剂AG825进行干预,对水飞蓟素的作用机制进行初步探讨。结果:水飞蓟素对两种乳腺癌细胞有不同程度的抑制作用,其中对MCF-7细胞的作用较强,IC50≤0.02%,而对SK-BR-3的作用较弱。Her-2抑制剂AG825可增加SK-BR-3细胞对药物的敏感性,抑制了水飞蓟素作用后该细胞在软琼脂中集落的形成。结论:水飞蓟素在体外对MCF-7细胞具有明显的抑制作用,而AG825可增强SK-BR-3细胞对药物的敏感性。因此,SK-BR-3细胞中Her-2的高表达可能是该细胞对水飞蓟素敏感性差的原因,而水飞蓟素也可能通过Her-2调节某个或某几个下游分子起作用。  相似文献   
3.
Purpose: We studied the effects of purine depletion on the cell cycle using a specific inhibitor of de novo purine biosynthesis, AG2034, an inhibitor of glycinamide ribonucleotide formyltransferase (GARFT). Methods: Cytotoxicity was determined by clonogenic assays, and cell cycle perturbations by flow cytometry. Ribonucleotide pools were measured by anion exchange high-pressure liquid chromatography, and DNA strand-breaks were determined by alkaline elution and by the TUNEL assay. Results: When cells were maintained in standard tissue culture medium, which contained 2.2 μM folic acid, AG2034 was cytostatic in all the cell lines tested. Under low-folate conditions (50 nM folic acid), AG2034 caused up to 50% cell death in cell lines that possessed a functional G1 checkpoint (A549, MCF-7), but was only cytostatic to the remaining cells, even at very high concentrations (100 μM ). In contrast, AG2034 at 10 nM or 100 nM killed all the cells in cultures of HeLa/S3 or SW480 cells, which lack a functional G1 checkpoint. Flow cytometry studies indicated that in G1 checkpoint-competent cells, AG2034 caused a G1 arrest. Those cells (up to 50%) that were already in S phase died, but the cells that were in G1 arrest maintained viability, based upon clonogenic assays, for many days. In G1 checkpoint-deficient cells, no G1 arrest was seen after AG2034 treatment, all cells progressed into S phase, and all cells died. Measurement of DNA strand-breaks, either by alkaline elution or by the dUTP end-labelling technique, indicated no DNA strand-breaks 24 h after AG2034 treatment, indicating that purine nucleotide depletion can trigger the G1 checkpoint in the absence of DNA damage. Conclusion: Purine depletion causes slow cell death in cells that have passed the G1 checkpoint, but cytostasis in cells that are arrested at the G1 checkpoint. The GARFT inhibitor, at physiological folate concentrations, thus causes selective cytotoxicity to cells lacking a functional G1 checkpoint. Received: 8 May 1997 / Accepted: 26 June 1997  相似文献   
4.
落叶松阿拉伯半乳聚糖滴丸制备工艺及其速释机制研究   总被引:1,自引:0,他引:1  
李津明 《中国中药杂志》2005,30(16):1249-1251
目的:研究落叶松阿拉伯半乳聚糖滴丸的制备工艺并初步探讨其速释机制。方法:采用正交设计对滴丸制备工艺进行优化,并通过相图分析和DSC分析研究滴丸的速释机制。结果与结论:滴丸制备最佳的工艺条件为药液温度75℃,二甲基硅油冷凝液上部温度30℃,滴头与冷凝液的距离6cm,滴速为30滴/min;相图分析和DSC分析结果显示在AG-PEG4000固体分散体中形成了某种形式的复合物,使熔点降低,药物在基质中的溶解度增加而达到速释。  相似文献   
5.
Curcumin (diferuloylmethane) is a phenolic compound present in turmeric and is ingested daily in many parts of the world. Curcumin has been reported to cause inhibition on proliferation and induction of apoptosis in many human cancer cell lines, including non‐small cell lung cancer cells (NSCLC). However, the clinical application of curcumin is restricted by its low bioavailability. In this report, it was observed that combined treatment of a low dosage of curcumin (5–10 µ m ) with a low concentration (0.1–2.5 µ m ) of small molecule inhibitors, including AG1478, AG1024, PD173074, LY294002 and caffeic acid phenethyl ester (CAPE) increased the growth inhibition in two human NSCLC cell lines: A549 and H1299 cells. The observation suggested that combined treatment of a low dosage of curcumin with inhibitors against epidermal growth factor receptor (EGFR), insulin‐like growth factor 1 (IGF‐1R), fibroblast growth factors receptor (FGFR), phosphatidylinositol 3‐kinases (PI3K) or NF‐κB signaling pathway may be a potential adjuvant therapy beneficial to NSCLC patients. Copyright © 2011 John Wiley & Sons, Ltd.  相似文献   
6.
[目的]探讨促性腺激素释放激动剂(GnRH-a)联合宫内放置左炔诺孕酮宫内缓释系统(LNG-IUS)对子宫内膜异位症(EMT)患者术后复发、痛经程度及性激素、糖抗原125(CA125)水平的影响.[方法]选取在陕西省宝鸡市眉县人民医院拟行腹腔镜手术的EM T患者107例,按照随机数表法分为观察组(n=54)和对照组(n...  相似文献   
7.
目的:探讨窒息新生儿血液阴离子间隙(AG)与新生儿缺氧缺血性脑病(HIE)发生率间的关系,以助早期诊治。方法:采用全自动血气分析仪对95例窒息新生儿进行外周动脉血血气分析,同时进行血电解质检测,计算具体的AG值。结果:窒息新生儿存在轻到中度的酸中毒,正常AG组与高AG组之间pH值和BE值差别无显著意义(P(0.05)。但两组之间HIE的发生率差异有显著性意义(P(0.05)。结论:AG值可作为预测窒息新生儿HIE的重要指标,指导临床诊断和治疗。  相似文献   
8.

Aim:

Paeoniflorin from Chinese herb Paeoniae Radix has been shown to ameliorate middle cerebral artery occlusion-induced ischemia in rats. The aim of this study was to investigate the mechanisms underlying the neuroprotective action of PF in cultured rat cortical neurons.

Methods:

Primary cultured cortical neurons of rats were subjected to oxygen-glucose deprivation and reoxygenation (OGD/R) insult. Cell survival was determined using MTT assay. HEK293 cells stably transfected with A1R (HEK293/A1R) were used for detailed analysis. Phosphorylation of the signaling proteins was evaluated by Western blot or immunoprecipitation. Receptor interactions were identified using co-immunoprecipitation and immunofluorescence staining.

Results:

Paeoniflorin (10 nmol/L to 1 μmol/L) increased the survival of neurons subjected to OGD/R. Furthermore, paeoniflorin increased the phosphorylation of Akt and ERK1/2 in these neurons. These effects were blocked by PI3K inhibitor wortmannin or MEK inhibitor U0126. Paeoniflorin also increased the phosphorylation of Akt and ERK1/2 in HEK293/A1R cells. Both A1R antagonist DPCPX and EGFR inhibitor AG1478 not only blocked paeoniflorin-induced phosphorylation of ERK1/2 and Akt in HEK293/A1R cells, but also paeoniflorin-increased survival of neurons subjected to OGD/R. In addition, paeoniflorin increased the phosphorylation of Src kinase and activation of MMP-2 in HEK293/A1R cells. Both Src inhibitor PP2 and MMP-2/MMP-9 inhibitor BiPs not only blocked paeoniflorin-induced phosphorylation of ERK1/2 (and Akt) in HEK293/A1R cells, but also paeoniflorin-increased survival of neurons subjected to OGD/R.

Conclusion:

Paeoniflorin promotes the survival of cultured cortical neurons by increasing Akt and ERK1/2 phosphorylation via A1R-mediated transactivation of EGFR.  相似文献   
9.
Endocannabinoids and liver disease--review.   总被引:4,自引:0,他引:4  
AIMS: Endocannabinoids are endogenous compounds that bind to the same receptors as tetrahydrocannabinol, the active component in marijuana and hashish. They have been found to have many physiological and patho-physiological functions, including mood alteration, control of feeding and appetite, motor and co-ordination activities, analgesia, immune modulation and gut motility. In this review we aim to elucidate current knowledge as to their role in liver physiology and disease. METHODS: The major findings published to date concerning endocannabinoids and liver disease are described, and their implications with regard to understanding disease mechanisms, and the development of new treatments is considered. RESULTS: Recently, endocannabinoids have been implicated in the hemodynamic alterations occurring in cirrhosis. These changes appear to be mediated via specific cannabinoid receptors (CB1) on splanchnic and hepatic vascular endothelium. Plasma levels of endocannabinoids also seem to be elevated in hepatitis, and are involved in apoptosis of hepatocytes by a membrane mechanism not related to a specific receptor. Other studies suggest a beneficial role for cannabinoids in reducing the inflammation of experimental hepatitis. In an animal model of acute hepatic failure, both endocannabinoids and the antagonist to the CB1 receptor have been found to have a beneficial effect on neurological and cognitive function. CONCLUSIONS: Endocannabinoids appear to be involved in several aspects of acute and chronic liver disease, including vascular changes, modulation of inflammatory process and neurological function, Further research may provide new insights into the pathophysiology of liver disease, as well as a basis for novel treatment modalities.  相似文献   
10.
张顺  刘凡  张运涛  汪涌 《实用医学杂志》2005,21(20):2227-2230
目的:探讨表皮生长因子受体阻滞剂TyrophostinAG1478对肾癌GRC-1细胞的诱导凋亡作用及其机制,为肾癌的生物学特征研究和药物治疗提供理论依据。方法:将不同浓度的AG1478作用于体外培养的肾癌GRC-1细胞,以研究表皮生长因子受体信号转导阻滞剂对细胞增殖和细胞周期分布的影响。结果:AG1478抑制肾癌GRC-1细胞的增殖,诱导细胞周期停留在G1期,诱导肾癌GRC-1细胞凋亡。结论:表皮生长因子受体特异性阻滞剂可抑制肾肿瘤细胞的增殖,有望成为抗肾脏恶性肿瘤药物。  相似文献   
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