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61.
目的:探讨姜黄素对低氧性肺动脉高压(HPH)的作用及其机制。方法:同时研究肺动脉平滑肌细胞(PASMCs)和SD大鼠肺组织,PASMCs和SD大鼠都设置为常氧组(N)、低氧组(H)、低氧+姜黄素组(HC)3组。CCK-8法测3组PASMCs细胞活力,Western blot法检测3组PASMCs和肺匀浆中NLRP3、Caspase-1及IL-1β蛋白表达差异。血流动力学检测3组大鼠的平均肺动脉压(mPAP)及右心肥大程度,HE染色观察3组大鼠肺血管重塑程度。结果:与N组比,H组PASMCs的数量有明显增加(P<0.05),H组PASMCs和肺匀浆中NLRP3、Caspase-1、IL-1β蛋白表达均上升(均P<0.05),H组大鼠的mPAP及右心肥大指数明显升高(均P<0.05),发生明显肺血管重塑;与H组比,HC组PASMCs的数量明显降低(P<0.05),PASMCs和肺匀浆中NLRP3、Cas-pase-1、IL-1β蛋白表达均下降(均P<0.05),HC组大鼠的mPAP及右心肥大指数明显降低(均P<0.05),肺血管重塑改善。结论:姜黄素可能通过抑制NLRP3/Caspase-1/IL-1β轴,改善低氧PASMCs异常增殖、HPH大鼠肺血管重塑和右心肥大,降低肺动脉压力。 相似文献
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64.
Xiao Chen Xuliang Chen Xiangxiang Shi Zhan Gao Zhigang Guo 《Clinical and experimental pharmacology & physiology》2020,47(7):1182-1192
Curcumin (Cur) has various pharmacological activities, including anti-inflammatory, antiapoptotic and anticancer effects. However, there is no report on the effect of Cur on endothelial cell fibrosis. This study was designed to investigate the effect and mechanism of Cur on endothelial cell fibrosis. An endothelial cell fibrosis model was established by using transforming growth factor (TGF) induction. Proliferation assays, qRT-PCR, western blotting and immunostaining were performed to investigate the effects and mechanism of Cur on endothelial cell fibrosis. We found that in human umbilical vein endothelial cells (HUVECs), TGF-β1 treatment significantly decreased the expression of nuclear factor erythroid-2-related factor 2 (NRF-2), dimethylarginine dimethylaminohydrolase-1 (DDAH1), and VE-cadherin, the secretion of cellular nitric oxide (NO) and the activity of nitrous oxide synthase (NOS), while asymmetric dimethylarginine (ADMA) and the release of inflammatory factors were elevated. Immunofluorescence showed decreased CD31 and increased α-smooth muscle actin (α-SMA). Overexpression of NRF-2 significantly attenuated the effects of TGF-β1, while downregulation of DDAH1 potently counteracted the effect of NRF-2. In addition, ADMA treatment resulted in similar results to those of TGF-β1, and Cur significantly attenuated the effect of TGF-β1, accompanied by increased VE-cadherin, DDAH1 and NRF-2 and decreased matrix metalloproteinase-9 (MMP-9) and extracellular regulated protein kinases 1/2 (ERK1/2) phosphorylation. The NRF-2 inhibitor ML385 had the opposite effect as that of Cur. These results demonstrated that Cur inhibits TGF-β1-induced endothelial-to-mesenchymal transition (EndMT) by stimulating DDAH1 expression via the NRF-2 pathway, thus attenuating endothelial cell fibrosis. 相似文献
65.
目的 探讨姜黄素(curcumin)对乳腺癌细胞中顺铂(Cisplatin,CDDP)治疗敏感性的影响及其可能机制.方法 CCK-8检测、Hoechst染色观察CDDP、姜黄素单独及联合用药48 h对MCF7细胞增殖抑制和细胞凋亡的影响;Western blot分析MCF7细胞在CDDP(0、1.25、2.5、5、10、20 μg/mL)、姜黄素(0、1、5、20、30、50、100 μmol/L)单独及联合处理后FEN1(flap endonuclease 1)表达水平的变化;CCK-8检测沉默FEN1对MCF7细胞中CDDP敏感性的影响.结果 CDDP、姜黄素均可以剂量依赖方式抑制MCF7细胞增殖,其IC50分别为5、30 μmol/L;与单独2μg/mLCDDP处理组比较,2μg/mL CDDP联合20-μmol/L姜黄素、30 μmol/L姜黄素处理组对细胞增殖的抑制效应明显增强[分别为(84.1±0.8)%、(51.1±0.5)%、(29.4±0.3)%,P<0.05];与单独20μmol/L姜黄素处理组比较,20 μmol/L姜黄素联合2μg/mL CDDP、5μg/mL CDDP处理组对细胞增殖的抑制效应也明显增强[分别为(76.9±0.7)%、(42.4±0.3)%、(31.6±0.4)%,P<0.05];2μg/mL CDDP联合20 μmol/L姜黄素组的细胞凋亡明显增强(P<0.05);与Control siRNA组比较,FEN1 siRNA+CDDP组可显著增强CDDP抑制MCF7细胞增殖的敏感性[(25.4±0.3)%vs(18.7±0.2)%,P<0.05];CDDP增殖抑制无效浓度或低浓度时,FEN1蛋白的表达随CDDP的处理剂量依赖性上调,而姜黄素可剂量依赖性下调FEN1蛋白表达;与单独CDDP和姜黄素处理组比较,2μg/mL CDDP联合20 μmol/L姜黄素组可显著降低FEN1蛋白表达(P<0.05).结论 姜黄素可增强CDDP对乳腺癌细胞的敏感性,其机制与降低细胞FEN1的表达有关. 相似文献
66.
The present study enumerates the attenuating effects of curcumin and α-tocopherol against propoxur induced oxidative DNA damage in human peripheral blood mononuclear cells (PBMC). Cultured cells were isolated from peripheral blood of healthy volunteers, and were exposed to varying concentrations of propoxur (0–21?μg/ml) for 6, 12, and 24?h, and in combination with curcumin (9.2?μg/ml) or α-tocopherol (4.3?μg/ml) or both. Cytotoxic effect of propoxur was examined by MTT assay. The role of oxidative stress beneath the cytotoxicity of propoxur was evaluated by the measurement of reduced glutathione (GSH), malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OH-dG) levels in cell lysate. A concentration-dependent cell death, depletion of GSH, an increase in the level of both MDA and 8-OH-dG were observed. Co-treatment with curcumin or α-tocopherol significantly attenuates depleted GSH, decrease in MDA and 8-OH-dG levels in propoxur exposed cells (p?0.05). The results of the present study provide experimental evidence of involvement of oxidative stress in propoxur-mediated genotoxicity in human PBMC and highlight the antioxidant role of curcumin and α-tocopherol following propoxur exposure. 相似文献
67.
目的观察姜黄素(curcumin)对糖基化终末产物(AGEs)诱导的软骨细胞凋亡及线粒体功能损伤的作用,并探讨相关机制是否与姜黄素上调过氧化物酶体增殖物激活受体-γ(PPARγ)相关。方法原代培养家兔膝关节软骨细胞;TUNEL染色法检测细胞凋亡;Rhodamine-123试剂盒检测线粒体跨膜电位(△Ψm);ATP试剂盒检测线粒体ATP生成;分光光度法检测caspase-3活性;Western blot检测PPARγ、细胞色素C、Bax及Bcl-2蛋白表达;real-time PCR检测PPARγmRNA含量;DNA-binding法检测PPARγ活性。结果 AGEs(200 mg·L-1)可明显诱导兔软骨细胞凋亡,同时线粒体跨膜电位(△Ψm)降低、ATP生成减少,caspase-3活性增加,细胞色素C释放增加,Bax/Bcl-2的比值增加;线粒体通透性转换孔的抑制剂环孢霉素A(Cs A,100 nmol·L-1)可以明显抑制AGEs诱导的细胞凋亡;PPARγ特异性激动剂吡格列酮及姜黄素均可明显抑制AGEs诱导的软骨细胞凋亡及线粒体功能损伤,给予PPARγ特异性抑制剂GW9662 10μmol·L-1预处理后,可以明显拮抗姜黄素的保护作用。同时,姜黄素可以明显上调AGEs诱导的PPARγ活性的降低,并伴随PPARγ相应的mRNA及蛋白表达水平的升高。结论姜黄素通过上调PPARγ,有效地保护AGEs诱导的软骨细胞线粒体损伤,从而抑制AGEs诱导的软骨细胞凋亡。 相似文献
68.
AbstractDeveloping drug formulations for poorly water-soluble drugs is a major challenge for pharmaceutical industries as the poor water solubility limits bioavailability of these drugs. Production of nanoparticles/microparticles of these drugs is one of the ways to improve dissolution rates by increasing interfacial area for dissolution. Curcumin, a compound obtained from the rhizome of curcuma longa (turmeric roots), is a pharmaceutically viable molecule. However, poor aqueous solubility limits its therapeutic use. In this work, we report studies conducted to continuously produce aqueous suspensions of curcumin nano/micro particles. Influence of process parameters such as ultrasound, additives, and solvent to antisolvent ratio on polymorphic outcome and morphology of precipitated particles has been investigated. Ultrasound was found to greatly influence the polymorphic form and the morphology of precipitated particles. Nucleation rates, mixing time, and solid–liquid interfacial energies were also estimated to understand the effect of various processing parameters on the precipitation process. 相似文献
69.
Pancreatic cancer is one of the most malignant cancers with a high mortality rate. Some types of pancreatic cancer cells overexpress epidermal growth factor receptor (EGFR), which is a potential target for anticancer agents. In this study, we examined the effect of epidermal growth factor (EGF)-conjugated liposomes containing curcumin (EGF-LP-Cur) on three different EGFR-expressed human pancreatic cancer cell lines, BxPC-3, Panc-1 and Mia Paca-2. We have demonstrated that it is feasible to prepare liposomal vesicles of EGF-LP-Cur and that it is stable in the liquid vehicle at ambient conditions for three weeks. In addition, the formulation of curcumin had higher cytotoxicity on BxPC-3 than on any other cells. It is also shown that the cellular uptake of curcumin on BxPC-3, which is essential for the cytotoxicity, is associated with EGFR-mediated mechanism of action. In summary, our results have showed that targeting EGFR with EGF-conjugated curcumin liposomes enhanced the antitumor activity of curcumin against human pancreatic cancer cells. 相似文献
70.
目的 优化RGD环肽修饰的姜黄素(curcumin,Cur)/黄芩苷(baicalin,Bai)共递送靶向纳米脂质体(RGD-Cur/Bai-Lip)的制备工艺并进行表征评价。方法 采用乙醇注入法制备RGD-Cur/Bai-Lip,首先通过Plackett-Burman筛选实验确定超声时间、胆脂比、水合温度作为制备RGD-Cur/Bai-Lip的关键因素,然后采用Box-Behnken响应面法进行工艺优化,以姜黄素包封率、黄芩苷包封率、总载药量为考察指标,采用AHP-复相关系数法-拉开档次法进行多指标组合赋权以确定各指标权重系数并计算综合评分,从而确定RGD-Cur/Bai-Lip的最优处方及关键工艺参数。最后对其形态、粒径电位、稳定性、体外释放度及溶血性等进行表征评价。结果 优选得到的最佳工艺为胆脂比1:12,水合温度60℃,探头超声时间为10 min。RGD-Cur/Bai-Lip外观澄清透明,呈亮黄色,对光可视淡蓝色乳光,透射电子显微镜下观察形态圆整、分散均匀。平均粒径为(101.10±0.62)nm,多分散系数(PDI)为0.191 0±0.014 3,Zeta电位为(1.59±0.07)mV,姜黄素包封率为(94.28±4.51)%,黄芩苷包封率为(76.93±1.35)%,总载药量为(2.27±0.09)%。7 d内稳定性良好,无溶血性,并具有一定的缓释作用。结论 优化处方后制备的RGD-Cur/Bai-Lip包封率高,粒径分布均匀,7 d内较稳定,无溶血性,并具有一定的缓释作用,为RGD-Cur/Bai-Lip的后续抗肝纤维化体内外研究提供了制剂基础。 相似文献