姜黄素体内外逆转结肠癌的5-氟尿嘧啶耐药研究及机制探讨

摘要：目的 探究姜黄素在体内外对结肠癌5-氟尿嘧啶（5-FU）耐药的逆转作用及其相关机制。 方法 以SW480结肠癌细胞为亲代细胞,构建5-FU耐药细胞株SW480R,采用MTT法检测SW480R细胞的耐药指数以及不同浓度的姜黄素对SW480R细胞增殖能力的影响;流式细胞术检测姜黄素对SW480R细胞周期和凋亡的影响;Western blot检测姜黄素对SW480R细胞上皮-间充质转化（epithelial-mesenchymal transition, EMT）相关蛋白以及Wnt信号通路相关蛋白的影响;采用裸鼠移植瘤模型检测肿瘤体积变化情况,计算姜黄素的体内抑瘤率,Western blot检测肿瘤组织中相关蛋白变化。结果 SW480R的耐药指数为12.16,姜黄素能够剂量依赖性地抑制SW480R细胞的增殖,阻滞SW480R细胞周期于G0/G1期,以及诱导SW480R细胞凋亡;Western blot结果表明姜黄素能够在体内外抑制EMT和Wnt信号通路的活性;体内实验表明姜黄素能够有效抑制裸鼠移植瘤的生长。结论 姜黄素能够在体内外逆转结肠癌的5-FU耐药,其机制可能是通过调控Wnt信号通路从而抑制EMT的发生。     

Molecular signalling of a novel curcumin derivative versus Tadalafil in erectile dysfunction

The efficacy of a novel curcumin derivative (NCD) versus tadalafil in erectile signalling was assessed. Ten control male rats and 50 diabetic male rats were used and divided into the following: diabetic (DM), curcumin (CURC), NCD, tadalafil and NCD combined with tadalafil rat groups. Cavernous tissue gene expression of heme oxygenase‐1 (HO‐1), Nrf2, NF‐B and p38, enzyme activities of heme oxygenase (HO) and nitric oxide synthase (NOS), cGMP and intracavernosal pressure (ICP)/mean arterial pressure (MAP) were assessed. Results showed that 12 weeks after induction of diabetes, erectile dysfunction (ED) was confirmed by the significant decrease in ICP/MAP, a significant decrease in cGMP, NOS, HO enzyme activities, a significant decrease in HO‐1 gene and a significant increase in NF‐?β, p38 genes. Administration of all therapeutic interventions led to a significant increase in ICP/MAP, cGMP levels, a significant increase in HO‐1 and NOS enzymes, a significant increase in HO‐1, and Nrf2 gene expression, and a significant decrease in NF‐?β, p38 gene expression. NCD or its combination with tadalafil showed significant superiority and more prolonged duration of action. In conclusion, a tendency was observed that CURC and NCD have high efficacy and more prolonged duration of action in enhancing erectile function.     

姜黄素抗肿瘤新剂型研究进展

姜黄素是从姜科植物根茎中提取的相对分子量较小的多酚类物质,具有抗肿瘤抗炎、抗病毒、抗氧化等多种药理作用,随着现代医学发展,姜黄素抗肿瘤方面药理作用的分子机制被不断认识。肿瘤的形成和发展是一个多阶段的过程,药物干预可作用于其中的任何阶段,人类希望能找到安全、高效的肿瘤预防与治疗药物。食物来源的天然药物姜黄素因其具备较低的毒副作用、较高的安全性和较高的依从性,可被各类人群尤其是中低风险人群长期服用,而倍受关注。然而姜黄素的一些理化性质决定了其应用不尽理想,如何改善这些缺陷逐渐成为当今研究姜黄素的热点。该文将从天然食物来源的预防肿瘤药物姜黄素应用新剂型进行综述。     

Effects of curcumin on interleukin-23 and interleukin-17 expression in rat retina after retinal ischemia-reperfusion injury

Objective: This study aimed to investigate the effect of curcumin on the retinal structure and the expressions of interleukin-23 (IL-23) and IL-17 in the rat retina after retinal ischemia-reperfusion injury (RIRI). Methods: 150 Sprague-Dawley rats were randomly divided into RIRI group (MG), low-dose curcumin group (LDCG) and high-dose curcumin group (HDCG), (n = 50 per group). RIRI was generated by anterior chamber perfusion of normal saline to the right eye. The left eye served as a normal control group (NCG). Rats in LDCG and HDCG received an intraperitoneal injection of 20 mg/kg/d and 100 mg/kg/d curcumin respectively, at 30 min before RIRI and once daily after RIRI. Results: The morphological changes in HDCG group were improved as compared to MG and LDCG groups. Immunohistochemistry showed that IL-23 and IL-17 were mainly expressed in the ganglion cell layer and the inner nuclear layer of the retina. Low IL-23 and IL-17 expressions were observed in NCG, but increased significantly in MG and LDCG groups. Western blot assay and ELISA also showed that IL-23 and IL-17 expressions increased significantly after RIRI (vs. NCG, P<0.01). Moreover, the IL-23 expression reached a peak at 24 h, whereas IL-17 expression peaked at 72 h after RIRI. Curcumin reduced IL-23 and IL-17 expressions significantly in a dose-dependent manner (vs. MG, P<0.01). Conclusion: The IL-23 and IL-17 expressions increase after RIRI and curcumin significantly reduces retinal IL-23 and IL-17 expressions in a dose-dependent manner and is able to prevent the RIRI induced damage to the retina.     

Bacterial Biofilm Formation Using PCL/Curcumin Electrospun Fibers and Its Potential Use for Biotechnological Applications

Electrospun nanofibers are used for many applications due to their large surface area, mechanical properties, and bioactivity. Bacterial biofilms are the cause of numerous problems in biomedical devices and in the food industry. On the other hand, these bacterial biofilms can produce interesting metabolites. Hence, the objective of this study is to evaluate the efficiency of poly (Ɛ- caprolactone)/Curcumin (PCL/CUR) nanofibers to promote bacterial biofilm formation. These scaffolds were characterized by scanning electron microscopy (SEM), which showed homogeneous fibers with diameters between 441–557 nm; thermogravimetric analysis and differential scanning calorimetry (TGA and DSC) demonstrated high temperature resilience with degradation temperatures over >350 °C; FTIR and ¹H-NMR serve as evidence of CUR incorporation in the PCL fibers. PCL/CUR scaffolds successfully promoted the formation of Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa biofilms. These results will be valuable in the study of controlled harvesting of pathogenic biofilms as well as in metabolites production for biotechnological purposes.     

姜黄素烟酸酯对辐射诱导的巨噬细胞IL-1β、IL-18表达的影响*

目的 研究姜黄素烟酸酯对巨噬细胞受射线照射产生的炎症因子白细胞介素-1β（IL-1β）、白细胞介素-18（IL-18）的影响。方法 将巨噬细胞分为空白对照组、单纯照射组及不同浓度姜黄素烟酸酯组（1.0、3.0和9.0?μmol/L）,应用Western blotting检测IL-1β、IL-18的表达。结果 1.0、3.0和9.0?μmol/L的姜黄素烟酸酯组与单纯照射组比较,差异有统计学意义（P?<0.05）,各浓度姜黄素烟酸酯组IL-1β、IL-18的蛋白表达量较单纯照射组下降;单纯照射组IL-1β、IL-18的蛋白表达量较对照组升高（P?<0.05）。结论 姜黄素烟酸酯可抑制辐射诱导巨噬细内炎症因子IL-1β、IL-18的产生。     

姜黄素预处理对急性缺血再灌注模型大鼠肝脏的保护作用

目的：建立姜黄素预处理的大鼠急性肝脏缺血再灌注模型,初步探讨姜黄素对急性缺血再灌注后大鼠肝脏的保护作用。方法：10只SD大鼠随机分为假手术组（n=3）、溶剂对照组（n=3）和实验组（n=4）。实验组和溶剂对照组大鼠在进行急性肝脏缺血再灌注前分别腹腔注射姜黄素和1%羧甲基纤维素钠（CMC）进行预处理。假手术组大鼠不进行急性肝脏缺血再灌注。采用超高效液相色谱-质谱（UPLC-MS）联用法分析各组大鼠血清中姜黄素水平,胆管导管术和荧光分析法检测各组大鼠胆汁流量,丙二醛（MDA）试剂盒检测各组大鼠肝脏组织中MDA水平。结果：腹腔注射200mg·kg^-1姜黄素1h后大鼠血清中姜黄素水平达到（0.17±0.05）mg·L^-1,并在注射3h后降到检测线以下。实验组大鼠肝脏组织中MDA水平为（9.18±1.78）mmol·g^-1,低于溶剂对照组（527.54mmol·g^-1±237.38mmol·g^-1）和假手术组（162.73mmol·g^-1±90.50 mmol·g^-1）。实验组大鼠在缺血再灌注后胆汁流量恢复到基线的40%左右,与溶剂对照组比较差异无统计学意义（P>0.05）,假手术组大鼠胆汁流量则保持在基线水平。结论：姜黄素腹腔注射给药后能迅速进入大鼠血液循环,并在体内较快代谢,其水平在给药3h后降到检测线以下。姜黄素预处理能有效降低缺血再灌注后肝脏组织中MDA水平,对肝脏起到保护作用,但对恢复胆汁流量的效果不明显。     

姜黄素通过NLRP3/Caspase-1/IL-1β轴对低氧性肺动脉高压的干预作用

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。