白藜芦醇对戊四氮致痫大鼠脑脊液、血清S1OOB蛋白的影响

目的 研究白藜芦醇(Res)对戊四氮致痫大鼠脑脊液、血清S100B蛋白的影响.方法 采用戊四氮(PTZ)腹腔注射建立慢性癫痫模型,造模成功后予以Res(15 mg/kg·d)灌胃干预10 d;采用酶联免疫吸附法测定脑脊液、血清S100B蛋白含量,海马标本行Nissl染色.结果 经28 d连续给药,18只大鼠符合Racine点燃标准,Res干预组大鼠痫性发作潜伏期明显延长,且发作时间明显低于癫痫模型组、二甲基亚砜组(P＜0.05).海马Nissl染色提示Res干预对大鼠海马CA1、CA3区神经元有保护作用(P＜0.05),而对齿状回保护作用不明显(P＞0.05).Res干预组大鼠脑脊液、血清S100B蛋白含量低于癫痫模型组、二甲基亚砜组(P＜0.05).结论 Res降低PTZ致痫大鼠脑脊液、血清S100B蛋白含量,或许减缓癫痫发作脑损伤发挥神经保护作用.     

Resveratrol as an active ingredient for cosmetic and dermatological applications: a review

Resveratrol is now being increasingly used in cosmetology and dermatology. This polyphenolic phytoalexin present in large amounts in red grapes and berries has a number of scientifically proven health-promoting properties associated with a positive effect on the cardiovascular system, lowering the concentration of low-density lipoprotein, and the ability to inhibit the cyclooxygenases activity. Additionally, it has antiproliferative, anti-angiogenic, anti-inflammatory, antioxidant, and antimicrobial properties. Its popularity in cosmetology and dermatology is primarily associated with proven ability to penetrate the skin barrier and antiaging activity. It has been shown that formulations with resveratrol can stimulate the proliferation of fibroblasts and contributing to the increase in the concentration of collagen III. Resveratrol has an affinity for the estrogen protein receptors (both ERα and ERβ), thereby contributing to the stimulation of collagen types I and II production. Moreover, resveratrol also has the antioxidant properties, thus can protect cells against oxidative damage associated with the effects of free radicals and UV radiation on the skin by reducing the expression of AP-1 and NF-kB factors and it slows down the process of photoaging of the skin. This study reviews literature on the skin care properties of resveratrol and its dermal bioavailability, metabolism, and dermal safety of application.     

Resveratrol-induced apoptosis in human T-cell acute lymphoblastic leukaemia MOLT-4 cells

Resveratrol (RES) is a natural occurring phytoalexin that has been shown to have chemopreventive activity. Resveratrol acts both by suppressing cell proliferation and inducing apoptosis in a variety of cancer cell lines. In this study, we show that RES induces apoptosis in MOLT-4 acute lymphoblastic leukaemia cells by modulating three different pathways that regulate cells survival and cell death. We show for the first time that RES inhibits the survival signalling pathways Notch and their down stream effector and modulates the operation of interacting signalling systems. It induces an increase in the levels of the pro-apoptotic proteins p53, its effector p21waf and Bax. We also show that RES inhibits the PI3K/Akt pathway and activates Gsk-3beta. The data presented here demonstrate unequivocally that RES induces apoptosis by inhibiting the Notch pathway and markedly influencing the operation of the interacting apoptosis pathways mediated by p53 and PI3K/Akt. These data support findings from other laboratories that have suggested the use of RES as a chemopreventive agent. Here, we have identified potential signalling pathways influenced by RES and this could lead to the identification of the targets of RES-induced apoptosis and growth control.     

Effect of resveratrol on the metastasis of 4T1 mouse breast cancer cells in vitro and in vivo

We investigated the effects of resveratrol on metastasis in in vitro and in vivo systems. 4T1 cells were cultured in the presence of various concentrations (0-30 µmol/L) of resveratrol. For experimental metastasis, BALB/c mice were injected intravenously with 4T1 cells in the tail vein, and were orally administered various concentrations (0, 100, or 200 mg/kg Body weight) of resveratrol for 21 days. After resveratrol treatment, cell adhesion, wound migration, invasion, and MMP-9 activity were significantly decreased in a dose-dependent manner in 4T1 cells (P < 0.05). The numbers of pulmonary nodules were significantly decreased in mice fed the resveratrol (P < 0.05). The plasma MMP-9 activity was decreased in response to treatment with resveratrol in mice (P < 0.05). We conclude that resveratrol inhibits cancer metastasis both in vitro and in vivo, and this inhibition is likely due to the decrease in MMP-9 activity caused by resveratrol.     

白藜芦醇对大鼠脑创伤后TNF-α和IL-1β影响的实验研究

目的检测白藜芦醇治疗后脑创伤大鼠血清TNF-α和IL-1β的浓度变化,探讨白藜芦醇的脑保护作用。方法SD大鼠50只,随机分为对照组和治疗组,每组分伤后3h、12h、24h、48h、72h共5个时间点,各时间点每组动物5只。Feeney法自由落体致伤动物。治疗组给予白藜芦醇(50mg/kg体重)腹腔注射治疗,伤前1d治疗一次,伤后每天治疗一次;对照组同法给予等量生理盐水治疗。分别于伤后各时间点股静脉取血,静置分层后离心,取血清低温保存,放射免疫法检测血清TNF-α和IL-1β浓度。结果伤后治疗组TNF-α和IL-1β浓度比对照组明显降低。结论白藜芦醇可以降低伤后血清TNF-α和IL-1β浓度,对脑创伤有保护作用。     

白藜芦醇对人胃癌耐药细胞SGC-7901/5-FU生物学效应的影响及其作用机制

目的探讨白藜芦醇(resveratrol,RES)对5-氟尿嘧啶(5-fluorouracil,5-FU)耐药胃癌细胞(SGC-7901/5-FU)生物学效应的影响及其作用机制。方法用不同浓度(0μmol/L、10μmol/L、50μmol/L、200μmol/L、400μmol/L)的RES分别处理SGC-7901/5-FU细胞24 h、48 h与72 h,其次用100μmol/L浓度的RES与5-FU(5μmol/L)单独或联合处理SGC-7901/5-FU细胞48 h。CCK-8法检测细胞增殖情况,流式细胞术检测细胞凋亡情况,免疫荧光染色法观察细胞形态。RT-PCR检测多药耐药基因MDR1以及凋亡相关基因Bcl2与Caspase 3的mRNA表达水平,Western blot检测P-gp、Bcl2和Caspase 3蛋白的表达水平。结果不同浓度RES均能抑制SGC-7901/5-FU细胞增殖,且具有时间与剂量依赖效应;RES组、5-FU组及联合组均能诱导SGC-7901/5-FU细胞凋亡,细胞出现凋亡样形态改变,其中联合组变化最明显(P<0.001);RES组和联合组中MDR1 mRNA与P-gp蛋白表达水平均下降(P<0.05),且联合组变化更明显;RES组、5-FU组及联合组中Bcl2 mRNA与蛋白表达水平均下降(P<0.001),Caspase 3 mRNA与蛋白表达水平均上升(P<0.001),其中联合组变化最明显。结论RES通过下调多药耐药基因MDR1/P-gp蛋白表达抑制胃癌耐药细胞SGC-7901/5-FU细胞增殖并诱导细胞凋亡,降低细胞耐药性。     

白藜芦醇对损伤动脉再内皮化和内膜增生的影响

目的探讨白藜芦醇对大鼠主动脉内膜剥脱后内皮修复、内膜增生的影响及其潜在机制。方法54只雄性SD大鼠随机分为假手术组(n=9)、对照组(n=15)、小剂量[10 mg/(kg.d)]白藜芦醇组(n=15)和大剂量[50mg/(kg.d)]白藜芦醇组(n=15),术前2周至动物处死期间经灌胃器给药;术后1周、2周分别应用Ⅷ因子检测和伊文思蓝染色评价各组损伤血管内皮修复情况;术后2周、4周采用HE染色观察内膜增生情况;采用逆转录聚合酶链反应及免疫组织化学法评价术后1周4、周损伤血管的内皮型一氧化氮合酶mRNA和蛋白水平的表达;体外分离、培养大鼠外周血内皮祖细胞,并采用免疫组织化学法进行鉴定;通过倒置荧光显微镜计数双阳性细胞以评价各组术后1周的外周循环内皮祖细胞数量。结果10 mg/(kg.d)白藜芦醇明显促进术后1周及2周的内皮修复,而50mg/(kg.d)不能;10 mg/(kg.d)白藜芦醇显著抑制术后2周、4周的内膜增生,而50 mg/(kg.d)只能抑制术后4周的内膜增生,且效果不如前者;10 mg/(kg.d)白藜芦醇明显促进损伤血管的内皮型一氧化氮合酶mRNA水平和蛋白水平的表达,而50 mg/(kg.d)组与对照组无明显差异;与对照组相比,10 mg/(kg.d)白藜芦醇显著升高术后1周的外周血内皮祖细胞数量(32.46±6.52比21.58±3.69,P<0.05),而50 mg/(kg.d)白藜芦醇无明显差异(22.48±6.89比21.58±3.69,P>0.05)。结论小剂量白藜芦醇可上调损伤血管内膜的内皮型一氧化氮合酶表达、促进内皮祖细胞动员、加快内皮修复及抑制内膜增生;而大剂量白藜芦醇只能抑制术后4周的内膜增生。     

白藜芦醇减轻LPS诱导的牙周膜细胞损伤并抑制TLR4/NF-κB活化

目的:探究白藜芦醇(RES)对脂多糖(LPS)诱导的人牙周膜细胞(hPDLCs)损伤的保护作用.方法:体外培养并鉴定hPDLCs,将培养的hPDLCs随机分为5组:对照组、LPS(10 μg/ml)+RES(0、30、60、90tμmol/L)组,MTT法检测各组细胞增殖能力,ELISA检测各组细胞分泌TNF-α/IL-6水平,PCR和Western blot检测各组细胞TLR4/NF-κB mRNA和蛋白表达.结果:分离培养的hPDLCs抗波丝蛋白表达阳性,抗角蛋白表达阴性.与对照组比,LPS处理后细胞增殖能力明显降低,细胞分泌TNF-α/IL-6水平和TLR4/NF-κB mRNA和蛋白表达明显增加;30～90 μmol/L白藜芦醇预处理后,细胞增殖能力增加(P＜0.05),细胞分泌TNF-α/IL-6水平、TLR4/NF-κB mRNA以及蛋白表达则下调(P＜0.05),均呈现一定的浓度依赖性.结论:白藜芦醇可抑制TLR4/NF-κB活化并减轻LPS诱导的牙周膜细胞损伤.     

白藜芦醇通过调节 SIRT1/AMPK 信号通路保护氧-葡萄糖剥夺大鼠皮质神经元

目的：探讨白藜芦醇对单次和双次氧-葡萄糖剥夺(oxygen-glucose deprivation, OGD)原代皮质神经元沉默信息调节因子1(silent information regulator 1, SIRT1)、AMP 活化的蛋白激酶(AMP-activated protein kinase, AMPK)活性和 ATP 含量的影响及其可能的神经保护机制。方法皮质神经元取自18 d Wistar 大鼠胚胎,原代培养成功后通过2次OGD 制作体外反复缺血模型。采用台盼蓝染色法检测细胞存活率,蛋白质印迹法检测 SIRT1和磷酸化 AMPK 表达,去乙酰化酶荧光检测法检测 SIRT1活性,生物发光测定法检测 ATP 含量。结果与对照组比较,白藜芦醇(0．5μmol/L)预处理能显著增高单次和双次 OGD 后存活率(P 均<0．001)、ATP 含量(P 均=0．004)、SIRT1活性(单次：P =0．001;双次：P =0．002)以及 SIRT1(单次：P =0．029;双次：P =0．023)和磷酸化 AMPK (P 均=0．001)表达水平。结论白藜芦醇对单次和双次 OGD 皮质神经元均具有神经保护作用,其机制可能与上调 SIRT1/AMPK 通路和降低能量需求有关。     

白藜三醇通过下调microRNA-21减轻快速电刺激所致心房肌细胞电重构

目的:研究白藜三醇(resveratrol,RSV)对快速电刺激(rapid electrical stimulation,RES)导致乳鼠心房肌细胞电重构时微小RNA-21(microRNA-21,miR-21)表达的影响,探讨RSV通过miR-21参与电重构的可能机制。方法:采用胰酶、Ⅰ型胶原酶双酶法及差速贴壁法分离培养乳鼠心房肌细胞。通过RES建立乳鼠心房肌细胞房颤模型,心房肌细胞随机分为4组:空白对照(control)组、RSV组、RES组和RSV+RES组。为了证实RSV是否通过调控miR-21的表达参与电重构,除了上述4组,另增加过表达和沉默miR-21组:RES+阴性对照组(RES+NC组)、RES+miR-21 mimics组、RES+miR-21 mimics+RSV组、RES+miR-21 inhibitor组和RES+miR-21 inhibitor+RSV组。CCK-8法检测心房肌细胞活性以确定RSV最佳作用浓度及时间,q PCR法检测各组细胞内miR-21及L型钙离子通道CACNA1C、CACNB2 mRNA的表达水平,Western blot检测L型钙离子通道Cav1.2和Cavβ_2 的蛋白表达水平。结果:与control组相比,RES组miR-21表达明显上调(P0.05),加入RSV预处理后miR-21表达下调(P0.05)。与RES+miR-21 mimics组相比,RES+miR-21 mimics+RSV组miR-21表达下调(P0.05),而CACNA1C和CACNB2 mRNA及Cav1.2和Cavβ_2 蛋白表达量增加(P0.05)。与RES组比,RES+miR-21 inhibitor和RES+miR-21 inhibitor+RSV组的miR-21表达下调(P0.05),CACNA1C和CACNB2 mRNA及Cav1.2和Cavβ_2 蛋白表达量增加,但RES+miR-21 inhibitor组与RSV+RES组比,miR-21表达、CACNA1C和CACNB2 mRNA及Cav1.2和Cavβ_2 蛋白表达量的差异无统计学显著性。结论:在快速电刺激乳鼠心房肌细胞模拟房颤模型中,RSV干预可能通过下调miR-21表达而调控其下游靶基因这一途径来减轻心房肌细胞电重构。