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131.
目的 分析姜黄素抑制高迁移率族蛋白B1(HMGB1)-核转录因子κB(NF-κB)信号通路减轻脂多糖(LPS)诱导新生大鼠急性肺损伤(ALI)的作用。方法 将60只新生SD雄性大鼠随机分为对照组、模型组、地塞米松(阳性药,2 mg·kg-1)组和姜黄素低、中、高剂量(1.5、3.0、6.0 mg·kg-1)组,每组10只。除对照组外,所有大鼠采用腹膜内注射LPS (3 mg·kg-1)建立ALI模型。注射LPS约6 h后开始ip给药,每天1次,连续7 d,模型组和对照组大鼠ip等体积的0.1% DMSO。通过血氧分压(PaO2)和肺干湿质量比(W/D)评估新生大鼠肺水肿情况;HE染色检测各组大鼠肺组织损伤;ELISA法检测新生大鼠支气管肺泡灌洗液(BALF)氧化应激指标超氧化物歧化酶(SOD)、髓过氧化物酶(MPO)、丙二醛(MDA)和谷胱甘肽(GSH)水平,BALF中白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和HMGB1水平;Western blotting法检测大鼠肺组织胞核NF-κB、胞浆NF-κB和磷酸化核因子κB抑制因子α(p-IκBα)蛋白表达。结果 与对照组相比,模型组新生大鼠肺泡腔有渗出、肺组织结构紊乱、细胞核固缩深染、伴随大量的炎性细胞浸润,病理评分显著升高(P<0.01); PaO2、BALF中SOD和GSH水平显著降低(P<0.01);肺W/D,BALF中MPO和MDA水平,BALF中IL-6、TNF-α和HMGB1水平,NF-κB胞核/胞浆比例和胞浆p-IκBα蛋白表达水平显著升高(P<0.01)。与模型组相比,姜黄素高、中剂量组和地塞米松组大鼠肺组织病理损伤减轻,肺泡腔渗出、炎性细胞浸润明显减少,病理评分显著降低(P<0.05、0.01); PaO2、BALF中SOD和GSH水平显著升高(P<0.05、0.01);肺W/D,BALF中MPO、MDA水平,BALF中IL-6、TNF-α和HMGB1水平,NF-κB胞核/胞浆比例和胞浆p-IκBα蛋白表达水平显著降低(P<0.05、0.01)。结论 姜黄素可以通过抑制HMGB1-NF-κB信号通路减轻LPS诱导的新生大鼠ALI。  相似文献   
132.
结直肠癌是我国第3大常见癌症,发病率、死亡率逐年上升。由于耐药导致结直肠癌化疗失败的报道不断增多,迫切需要寻找新的药物作为化疗药物的增敏剂。以中药活性成分为研究重点,发现姜黄素、白藜芦醇、人参皂苷等中药活性成分可以通过调控相关蛋白表达、自噬、上皮间充质转化、癌症干细胞、有氧糖酵解等途径逆转结直肠癌耐药性。对逆转结直肠癌耐药性的中药活性成分及其药理作用机制加以总结,以期为结直肠癌治疗提供更多选择。  相似文献   
133.
目的:通过星点设计-效应面法(central composite design-response surface methodology ,CCD-RSM)优化姜黄素非离子表面活性剂囊泡(curcumin niosomes ,Cur-Nio)的制备工艺和处方,并进行质量评价。方法:采用薄膜分散-超声法以硬脂山梨坦(Span 60)和胆固醇作为载体材料制备Cur-Nio,以包封率、载药量、平均粒径为考察指标,以总评"归一值"为评价指标优化制备处方。以CCD-RSM选取最佳处方,用二项式进行拟合预测分析,按优化出的处方制备Cur-Nio,考察测定Cur-Nio粒径、PDI和Zeta电位,透射电镜观察Cur-Nio形态,差式扫描热及X-射线衍射分析结构特征及晶型是否有变化,并对其稳定性及体外释放进行考察。结果:Cur-Nio的制备最佳处方及工艺条件为Span 60与胆固醇的质量比值为3.096∶1、水化时间为65 min、水化体积为19.45 mL;优化后的处方制备出的Cur-Nio的平均粒径是(151.70±2.003)nm,PDI为0.21±0.013,Zeta电位为(-45.10±1.40) mV,包封率为(82.91±0.59)%;透射电镜观察Cur-Nio外观圆整;长期存放4 ℃具有一定稳定性;差式扫描热及X-射线衍射结果表明Cur以无定型或分子状态包裹在囊泡中;体外释放结果表明,与游离姜黄素溶液相比,具有明显缓释效果。结论:通过CCD-RSM优化后的Cur-Nio,制备工艺简单,外观圆整,粒径均匀,具有缓释作用,符合优化试验结果。有效提高了姜黄素的生物活性,可用于进一步研究。  相似文献   
134.
135.
Diabetic neuropathic pain, an important microvascular complication in diabetes mellitus, is recognized as one of the most difficult types of pain to treat. The underlying mechanisms of painful symptoms may be closely associated with hyperglycaemia but a lack of the understanding of its proper aetiology, inadequate relief, development of tolerance and potential toxicity of classical antinociceptives warrant the investigation of newer agents to relieve this pain. The aim of the present study was to explore the antinociceptive effect of insulin and its combinations with resveratrol and curcumin in attenuating diabetic neuropathic pain. The study also aimed to examine the effect of these combinations on tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) levels in streptozotocin (STZ) induced diabetic mice. Four weeks after a single intraperitoneal injection of streptozotocin (200 mg/kg), mice were tested in the tail immersion and hot-plate assays. Diabetic mice exhibited significant hyperalgesia along with increased plasma glucose and decreased body weights compared with control mice. Chronic treatment with insulin (10 IU/kg/day, s.c.) and its combinations with antioxidants (resveratrol 20 mg/kg or curcumin 60 mg/kg, p.o.) for 4 weeks starting from the 4th week of STZ injection significantly attenuated thermal hyperalgesia and the hot-plate latencies. There was a significant inhibition of TNF-alpha and NO levels when these drugs were given in combination compared with their effects per se. These results indicate an antinociceptive activity of resveratrol and curcumin and point towards the beneficial effect of these combinations with insulin in attenuating diabetic neuropathic pain, possibly through the participation of NO and TNF-alpha.  相似文献   
136.
目的 研究姜黄素激活过氧化物酶体增殖因子活化受体γ(PPARγ)信号对大鼠肝星状细胞(HSC)活化、基质金属蛋白酶(MMPs)活性和胞核核因子-κBp65(RelA)表达的影响。方法 采用肝脏原位灌流酶消化、Nycodenz密度梯度离心法分离大鼠HSC。药物处理后收集裂解细胞,Western blot检测PPARγ、α平滑肌肌动蛋白(αSMA)、Ⅰ型胶原、RelA。收集细胞培养上清,明胶酶谱法检测MMP2、9的活性。结果 随着HSC活化程度增加PPAR7表达水平不断下降,姜黄素上调其表达水平(P〈0.01),拮抗剂GW9662显著阻断这种作用(P〈0.01)。姜黄素抑制αSMA的表达、Ⅰ型胶原的生成以及胞核内活化RelA的表达(P〈0.01),显著升高MMP2、9的活性(P〈0.01)。结论 姜黄素激活PPARγ信号途径抑制HSC活化,升高MMP2、9活性,抑制/干扰NFκB的核转位。  相似文献   
137.
Biological, biochemical and physical stimuli activate inflammatory leukocytes, such as macrophages, resulting in induction and synthesis of proinflammatory proteins and enzymes, together with free radicals, as innate immune responses. On the other hand, chronic and dysregulated activation of some inducible enzymes, including NADPH oxidase (NOX), inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, have been shown to play pivotal roles in the development of certain inflammatory diseases such as oncogenesis. While the use of synthetic agents, especially those targeting molecules, is an attractive and reasonable approach to prevent carcinogenesis, it should be noted that traditional herbs and spices also exist along with their active constituents, which have been demonstrated to disrupt inflammatory signal transduction pathways. In this mini-review, the molecular mechanisms of activation or induction of NOX, iNOS and COX-2, as well as some food phytochemicals with marked potential to regulate those key inflammatory molecules, are highlighted. For example, 1'-acetoxychavicol acetate, which occurs in the rhizomes of the subtropical Zingiberaceae plant, has been shown to attenuate NOX-derived superoxide generation in macrophages, as well as lipopolysaccharide-induced nitric oxide and prostaglandin E(2) production through the suppression of iNOS and COX-2 synthesis, respectively. Notably, this phytochemical has exhibited a wide range of cancer prevention activities in several rodent models of inflammation-associated carcinogenesis. Herein, the cancer preventive potentials of several food phytochemicals targeting the induction of NOX, iNOS and COX-2 are described.  相似文献   
138.
Magnetic core–shell nanoparticles are one of the most interesting nanocarriers. Smart polymers can be attached to nanoparticles as a suitable shell. Cancer tissues, with higher temperature than normal one, are one of the best targets for these systems in which the polymeric shell shrinks and thus drugs are released. The aim of this research is to synthesize such a smart nanocarrier with a thermoresponsive shell. Magnetic nanoparticles are coated with poly(N‐isopropylacrylamide). Afterward, the as prepared nanoparticles are analyzed through different characterization methods (scanning electron microscope, Fourier‐transform infrared spectroscopy, carbon–hydrogen–nitrogen–sulfur elemental analysis, energy‐dispersive X‐ray spectroscopy) and their response to the temperature is investigated in different temperatures (37 and 40 °C). Results demonstrate that a biocompatible nanocarrier with the average size of about 35 nm and 83% entrapment efficiency for curcumin is successfully synthesized. The drug release process shows a controlled behavior over temperature. It has an increasing trend by increasing the temperature from 4 to 37 °C and then to 40 °C. Moreover, the cytotoxicity of drug loaded nanocarrier is obviously increased at 40 °C compared to 37 °C. It can be concluded that this new smart nanotheranostics agent can be successfully applied for cancer treatment.  相似文献   
139.
姜黄素抑制血管生成作用的实验研究   总被引:3,自引:0,他引:3  
目的研究姜黄素对血管生成和内皮细胞生长的影响。方法利用生长因子(VEGF和bFGF)诱导的鸡胚绒毛尿囊膜(CAM)血管增生模型观察姜黄素对血管生成的影响;利用培养的人脐静脉内皮细胞(HUVEC),采用MTT法观察不同时间、不同浓度姜黄素对内皮细胞增殖的抑制作用。结果姜黄素能明显抑制VEGF和bFGF诱导的CAM小血管生成,对内皮细胞增殖的抑制作用呈剂量和时间依赖性。结论姜黄素具有显著的抗血管生成作用。  相似文献   
140.
Background The function of peroxisome proliferator-activated receptor γ (PPARγ) in hepatic fibrogenesis remains largely unknown. Curcumin is a natural substance extracted form Curcuma Longa Linn and has a variety of pharmacological effects. In this study, the effects of curcumin on the proliferation, activation and apoptosis of rat hepatic stellate cells (HSCs) through PPARγ signaling were investigated. Methods HSCs were isolated from the normal Sprague Dawley rats through in situ peffusion of the liver with Pronase E and density-gradient centrifugation with Nycodenz. Cells were treated with curcumin, troglitazone, salvianolic acid B or GW9662. The effect on HSCs proliferation was determined by MTT colorimetry. Total RNA was extracted by TRizol reagent and gene levels were determined by semi-quantitative RT-PCR. Total cellular and nuclear protein were isolated and separated by 10% sodium dodecy Isulfate polyacrylamide gel electrophoresis. Protein levels were determined by Western blot. Cell apoptosis was detected by Hoechst 33258 staining. PPARγ subcellular distribution was detected by immunofluorescent staining. The activities of MMP-2 and 9 were measured by Gelatin zymograph assay. Results Curcumin suppressed HSCs proliferation in a dose-dependent manner. As HSCs underwent gradual activation with culture prolongation the PPARγ nuclear expression level decreased. Curcumin up-regulated PPARγ expression and significantly inhibited the production of a-SMA and collagen Ⅰ. PPARγ is expressed in the cytoplasm and nucleus and is evenly distributed in HSCs, but accumulated in the nucleus of HSCs and disappeared from cytoplasm after curcumin treatment. Hoechst 33258 staining showed that curcumin induced the apoptosis of culture-activated HSCs and significantly increased pro-apoptotic Bax expression and reduced anti-apoptotic Bcl-2 expression. Cyclin D1 gene, activated NFKB p65 protein and TGFβR-Ⅰ protein expression were down-regulated significantly by curcumin. The activities of MMP-2 and MMP-9 were enhanced significantly by curcumin. Conclusions Curcumin can inhibit the proliferation and activation of HSCs, induce the apoptosis of activated HSCs and enhance the activities of MMP-2 and MMP-9. The effects of curcumin are mediated through activating the PPARγ sianal transduction pathway and associated with PPARγ nuclear translocation/redistribution.  相似文献   
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