柚皮素对胰腺癌细胞PANC-1增殖和凋亡的影响

目的 探讨柚皮素对胰腺癌细胞PANC-1增殖和凋亡的影响及糖原合成酶激酶-3β(GSK-3β)在其中的作用。方法 PANC-1细胞根据随机数字表分为7组(每组12孔,细胞密度为2 500个/mm²):0μmol/L、50μmol/L、100μmol/L、200μmol/L、400μmol/L、control virus和GSK-3β virus组。0μmol/L组,加入相应体积溶剂;50μmol/L、100μmol/L、200μmol/L和400μmol/L分别在培养液中加入终浓度为50μmol/L、100μmol/L、200μmol/L和400μmol/L的柚皮素进行培养;Control virus组,感染了对照病毒的PANC-1细胞培养液中加入200μmol/L的柚皮素进行培养;GSK-3β组,感染了GSK-3β过表达慢病毒的PANC-1细胞培养液中加入200μmol/L柚皮素。CCK-8检测细胞活力,细胞计数仪测定细胞数量,流式细胞测量凋亡细胞百分比,Western blot方法检测Ki-67、cleaved caspase-3、GSK-3β和p-GSK-3...     

柚皮素对去卵巢所致大鼠骨质疏松症的影响

目的：观察柚皮素对去卵巢所致大鼠骨质疏松症的治疗作用。方法50只雌性SD大鼠随机分为假手术组、模型组、柚皮素低、中、高剂量组,每组10只。假手术组施行假手术,其余4组均行卵巢摘除术,术后4周开始灌胃给予35、70、140 mg/kg柚皮素。12周后分别检测5组大鼠血清雌二醇(E2)、孕激素(P)、抗酒石酸酸性磷酸酶( TRACP)、碱性磷酸酶( ALP)、骨钙素( BGP),尿液钙( Ca)、磷( P)及脱氧吡啶啉( DPD)、骨密度( GMD)、股骨三点弯曲应力、L5腰椎抗压缩载荷及骨小梁形态变化。结果与假手术组比较,模型组大鼠体重明显增加,子宫脏器系数明显降低,差异有统计学意义( P <0.05);柚皮素低、中、高剂量组大鼠体重较模型组明显降低,子宫脏器系数较模型组明显增加,差异有统计学意义( P <0.05),并呈剂量依赖性。与假手术组比较,模型组大鼠血清E2、P明显降低,差异有统计学意义( P <0.05);柚皮素低、中、高剂量组大鼠血清E2、P较模型组明显增加,差异有统计学意义( P <0.05),呈剂量依赖性。与假手术组比较,模型组大鼠血清TRACP及尿液Ca、P、DPD明显增加,差异有统计学意义(P<0.05);柚皮素低、中、高剂量组血清 TRACP及尿液 Ca、P、DPD较模型组明显降低,差异有统计学意义( P <0.05),且呈剂量依赖性。与假手术组比较,模型组大鼠血清ALP明显增加,BGP明显降低,差异有统计学意义( P <0.05);柚皮素低、中、高剂量组大鼠血清ALP较模型组明显降低,BGP较模型组明显增加,差异有统计学意义( P <0.05),呈剂量依赖性。与假手术组比较,模型组大鼠BMD明显降低,差异有统计学意义( P <0.05);柚皮素低、中、高剂量组大鼠BMD较模型组明显增加,差异有统计学意义( P <0.05),呈剂量依赖性。与假手术组比较,模型组大鼠股骨三点弯曲应力、L5腰椎抗压缩载荷明显降低,差异有统计学意义( P <0.05);柚皮素低、中、高剂量组大鼠股骨三点弯曲应力、L5腰椎抗压缩载荷较模型组明显增加,差异有统计学意义( P <0.05),呈剂量依赖性。与假手术组比较,模型组大鼠骨小梁面积百分数、骨小梁数、骨小梁厚度明显降低,骨小梁分离度明显增加,差异有统计学意义( P <0.05);柚皮素低、中、高剂量组大鼠骨小梁面积百分数、骨小梁数、骨小梁厚度较模型组明显增加,骨小梁分离度较模型组明显降低,差异有统计学意义( P <0.05),呈剂量依赖性。结论柚皮素对去卵巢所致大鼠骨质疏松症具有良好的治疗作用。     

柚皮素诱导肺腺癌A549细胞凋亡的研究

目的：研究柚皮素对肺腺癌A549细胞的增殖抑制及诱导凋亡作用。方法应用四甲基偶氮唑盐比色法（MTT法）观察柚皮素对A549细胞增殖的抑制作用;Hoechst 33342染色后于倒置荧光显微镜下观察柚皮素对A549细胞形态的影响;通过Annexin V-FITC/PI双染后流式细胞术检测柚皮素对A549细胞诱导凋亡的作用。结果柚皮素可抑制A549细胞的增殖,且呈现时效、量效依赖关系;Hoechst 33342染色倒置荧光显微镜下发现不同浓度柚皮素作用细胞48h后出现细胞核破裂、浓染,呈现明显的凋亡形态学特征;200μM、400μM 柚皮素作用细胞48h 后 A549细胞凋亡率分别为（12.15±2.14）%和（25.26±3.37）%。结论柚皮素可能通过诱导细胞凋亡从而发挥其抑制A549细胞增殖的作用。     

柚皮素对脂多糖诱导的H9c2心肌细胞炎症和凋亡的作用机制研究

目的探讨柚皮素对脂多糖(LPS)诱导的H9c2心肌细胞的炎症和凋亡的作用机制。方法将大鼠H9c2心肌细胞随机分为4组:空白对照组、模型组和低、高2个浓度实验组。用10μg·mL-1 LPS处理模型组和实验组的细胞造成细胞损伤,空白对照组用正常含血清培养液处理细胞。低、高2个浓度实验组分别加入5,20μmol·mL-1柚皮素处理12 h。用实时荧光定量-PCR法检测白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子α(TNF-α)基因的表达水平,缺口末端标记法检测心肌细胞凋亡情况(阳性细胞数与总细胞数比值),蛋白质印迹法检测B细胞淋巴瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)和核转录因子-κB (NF-κB)蛋白表达水平。结果空白对照组、模型组和低、高2个浓度实验组的IL-1β基因相对表达量分别为1.00±0.18,1.57±0.17,1.55±0.26和1.15±0.13;IL-6基因相对表达量分别为1.00±0.16,1.75±0.21,1.71±0.16和1.32±0.20;TNF-α基因相对表达量分别为1.00±0.15,2.68±0.17,2.65±0.23和1.51±0.18;心肌细胞凋亡率分别为(2.87±0.81)%,(13.82±1.34)%,(13.78±1.82)%和(7.32±0.64)%。上述指标:模型组与空白对照组比较,或高浓度实验组与模型组比较,差异均有统计学意义(均P<0.05)。蛋白结果的趋势与基因一致。结论柚皮素通过调控NF-κB通路改善脂多糖诱导的H9c2心肌细胞的炎症反应和细胞凋亡。     

柚皮苷和柚皮素对高脂血症大鼠同型半胱氨酸水平的影响

目的研究柚皮苷和柚皮素对高脂血症模型大鼠血清同型半胱氨酸水平的影响。方法将大鼠分为正常对照组、模型组、柚皮苷和柚皮素不同剂量给药组。正常对照组给予普通饲料,其余各组给予高脂饲料。正常对照组和模型组给予羧甲基纤维素,柚皮素组给予不同剂量柚皮素,柚皮苷组给予不同剂量柚皮苷,均灌胃给药。3周后测定大鼠血清同型半胱氨酸、三酰甘油、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇及极低密度脂蛋白胆固醇水平。结果模型组血三酰甘油和低密度脂蛋白胆固醇高于正常对照组(P<0.01);柚皮苷和柚皮素对大鼠血脂水平无明显影响;柚皮素低剂量组和柚皮苷低剂量组血清同型半胱氨酸水平明显降低(P<0.01,P<0.05)。相关性分析结果表明,大鼠血清同型半胱氨酸与血脂水平无明显相关性(P>0.05)。结论低剂量柚皮苷和柚皮素可降低大鼠血清同型半胱氨酸水平,但均对血脂无显著影响。     

柚皮素对四氯化碳致小鼠化学性肝损伤中氧化应激介质生成影响的实验研究

目的 考察柚皮素(黄酮类化合物)对小鼠化学性肝损伤中氧化应激介质生成的影响.方法 用灌胃法,小鼠连续7天预给予柚皮素(25,50,100 mg·kg-1),第7日经腹腔单次注射四氯化碳(CCl4,1 mL·kg-1)诱发化学性肝损伤.24 h后用紫外分光光度法测定血清转氨酶(ALT、AST)水平,氧化应激介质丙二醛(MDA)含量,及肝微粒体超氧化物歧化酶(SOD)活性;用单细胞凝胶电泳法检测肝细胞中DNA氧化损伤水平.结果 与对照组相比,CCl4化学损伤组小鼠的血清ALT水平显著升高,氧化应激介质生成增多,肝细胞DNA氧化损伤断裂显著增多.柚皮素预处理组,CC4l急性肝损伤中血清转氨酶水平虽然未见明显变化,但柚皮素在其高剂量组(100 mg·kg-1)可使MDA水平有下降趋势,SOD活性有升高趋势且可显著性地降低CCl4损伤所致彗星拖尾细胞的百分率.结论 预先给予柚皮素(25,50,100mg·kg-1)可使CCl4所致急性肝损伤中氧化应激反应减轻,并可显著降低肝细胞核DNA单链断裂氧化损伤水平.     

柚皮苷及其苷元柚皮素的呼吸系统药理作用研究概述

柚皮苷及其苷元柚皮素属于二氢黄酮类化合物,广泛存在于各类植物或各种中药中,具有多种生物活性,包括抗炎、抗氧化、改善糖脂代谢紊乱、神经保护、抗肝损伤、抗骨质疏松等。近年来,关于柚皮苷和柚皮素的呼吸系统药理作用备受关注。本团队系统研究了柚皮苷和柚皮素的镇咳、祛痰、抗肺部炎症等药理作用,并将柚皮苷研制成国家一类新药,目前已完成了Ⅰ期临床试验研究。本文就柚皮苷和柚皮素的镇咳、祛痰、抗肺部炎症、抗肺纤维化等呼吸系统药理作用的研究进展作一综述,以期为相关研究和临床应用提供参考。     

柚皮素治疗高脂血症的系统评价

目的系统评价柚皮素对血脂水平的影响,为高血脂及相关性疾病的基础研究提供资料。方法检索中国生物医学数据库、中国知网、维普数据库、万方数据库、PubMed、EMbase、Springer、Cochrane,查找柚皮素干预动物实验的文献,检索时限均为从建库至2018年12月16日。并对检索到的文献进行筛选,共纳入16篇,使用RevMan 5.3软件进行Meta分析。结果与模型组相比,柚皮素干预组TC (SMD=-1.42,95%CI:-2.16～-0.68)、TG (SMD=-1.37,95%CI:-2.05～-0.68)均低于模型组,HDL-C (SMD=0.63,95%CI:-0.02～1.28)、LDL-C (SMD=-0.18,95%CI:-0.90～0.54)与模型组比较差异无统计学意义。亚组分析结果显示,增大柚皮素干预量,TC、TG、HDL-C无明显改变。结论柚皮素具有降低TG、TC的作用,但对血浆LDC-C、血浆HDL-C变化无明显影响,且增大柚皮素干预剂量,降脂效果无明显改变。     

柚皮素对舌鳞癌Tca8113细胞增殖与凋亡的影响

目的探究柚皮素对人舌鳞癌Tca8113细胞株增殖及凋亡的影响及其机制。方法将细胞分为4组:空白对照组和低、中、高3个浓度实验组(柚皮素20,40,80μmol·L^-1),体外培养24 h。通过噻唑蓝比色法检测柚皮素对舌鳞癌Tca8113细胞抑制作用,流式细胞术检测细胞凋亡状况,蛋白质印迹法检测肿瘤蛋白p53(p53)、周期蛋白依赖激酶抑制剂1A(p21)、B淋巴细胞瘤-2(Bcl-2)和B淋巴细胞瘤-2相关X蛋白(Bax)蛋白表达(光密度比值)。结果 24 h后,空白对照组和低、中、高3个浓度实验组的Tca8113细胞抑制率分别为0,(16.19±1.74)%,(22.97±1.06)%和(48.72±1.95)%;这4组的细胞凋亡率分别为(1.66±0.53)%,(28.21±3.08)%,(47.21±2.54)%和(63.38±3.40)%;这4组的p53蛋白的相对表达量分别为0.53±0.11,0.66±0.09,0.78±0.10和0.90±0.13;这4组的p21蛋白的相对表达量分别为0.61±0.12,0.83±0.15,1.04±0.09和1.34...     

TXNIP介导的氧化应激在疾病中的作用机制

硫氧还蛋白相互作用蛋白(TXNIP)通过与硫氧还蛋白(Trx)的结合而抑制Trx的抗氧化作用,促进了活性氧簇(ROS)的产生与积聚,诱发内质网应激与线粒体应激,最终可诱导炎症或细胞凋亡。TXNIP所介导的氧化应激在糖尿病及其并发症(糖尿病肾病、糖尿病视网膜病变等)、动脉粥样硬化、缺血/再灌注损伤、癌症(肝细胞癌、膀胱癌、乳腺癌、白血病)等疾病的发生、发展过程中起着重要的调控作用。该文就TXNIP介导的氧化应激在相关疾病中的作用机制及研究进展进行综述。     

四烯甲萘醌保护成骨细胞氧化损伤的作用研究

目的 考察四烯甲萘醌(MK₄)对成骨细胞氧化损伤的保护作用,阐明MK₄防治骨质疏松作用机制。方法 采用过氧化氢(H₂O₂)刺激小鼠成骨细胞系（MC3T3-E1）氧化应激模型,考察细胞活力、ALP活性和骨结节面积,DCFH-DA法检测活性氧(ROS)水平,JC-1检测线粒体膜电势,Annexin V-FITC/PI法检测细胞凋亡率,RT-PCR法考察氧化应激相关基因FoxO1、FoxO3、SOD、Bcl-2和bax等的mRNA表达。结果 10 μmol/L四烯甲萘醌能显著提高H₂O₂刺激的成骨细胞增殖、ALP活性、骨结节形成面积和增强细胞膜电势,显著降低H₂O₂刺激的成骨细胞内丙二醛和活性氧水平,同时显著降低成骨细胞凋亡率和细胞凋亡因子bax/Bcl-2的mRNA表达水平,显著提高抗氧化酶SOD和转录因子FoxO1、FoxO3的mRNA表达。结论 四烯甲萘醌可通过调控FoxO通路保护成骨细胞氧化损伤和通过下调bax/Bcl-2比例,降低成骨细胞凋亡。     

氧化应激致PC12细胞凋亡的信号传导途径的研究进展

PC12细胞被广泛用于神经细胞功能、分化、凋亡和神经递质分泌,以及潜在的分子机制的研究。氧化应激可导致PC12细胞凋亡,其作用方式为激活对氧化还原反应敏感的细胞信号传导,主要与丝裂原活化蛋白激酶、线粒体凋亡及NF-κB信号传导途径有关。本文综述了氧化应激致PC12细胞凋亡的信号传导途径,旨在为神经系统氧化应激相关疾病的抗氧化剂药物治疗和凋亡信号途径药物干预治疗提供理论依据。     

白芍总苷对糖尿病大鼠心肌氧化应激和细胞凋亡的影响及机制研究

目的 探讨白芍总苷(total glucosides ofpaeony,TGP)对糖尿病大鼠心肌氧化应激和细胞凋亡的影响及其机制.方法 取120只SD大鼠按随机数字表法分为对照组、模型组、二甲双胍(Met,200 mg/kg)组和TGP低、中、高剂量(50、100、200 mg/kg)组,每组20只;采用一次性ip链脲...     

Acrylonitrile induced apoptosis via oxidative stress in neuroblastoma SH-SY5Y cell

Acrylonitrile (ACN) is a chemical that is widely used in the production of plastics, acrylic fibers, synthetic rubbers and resins. It has been reported that ACN can cause oxidative stress, a condition which is well recognized as an apoptotic initiator; however, information regarding ACN-induced apoptosis is limited. This present study investigated whether ACN induces apoptosis in human neuroblastoma SH-SY5Y cells, and whether its apoptotic induction involves oxidative stress. The results showed that ACN caused activation of caspase-3, a key enzyme involved in apoptosis, in a dose- and time-dependent manner. Detection of sub-G1 apoptotic cell death and apoptotic nuclear condensation revealed that ACN caused an increase in the number of apoptotic cells indicating ACN induces apoptosis in SH-SY5Y cells. ACN dose- and time-dependently increased the level of proapoptotic protein, Bax. Pretreatment with N-acetylcysteine (NAC), an antioxidant, attenuated caspase-3 activation by ACN, as evidenced by a reduction in proteolysis of PARP, a known caspase-3 substrate, as well as in the number of sub-G1 apoptotic cells. Moreover, induction of Bax by ACN was abolished by NAC. Taken together, the results indicate that ACN induces apoptosis in SH-SY5Y cells via a mechanism involving generation of oxidative stress-mediated Bax induction.     

Lethal concentration of perfluoroisobutylene induces acute lung injury in mice mediated via cytokine storm,oxidative stress and apoptosis

Perfluoroisobutylene (PFIB) is a highly toxic gas that targets the lungs. Low-level inhalation of the gas can lead to acute lung injury (ALI), pulmonary edema and even death. No specific anti-PFIB drugs are currently available and the pathogenesis of PFIB-induced ALI is not fully understood. Early direct oxidative injury and a secondary hyper-inflammatory response are recognized as the primary mechanisms of PFIB-induced ALI. In the present study, our data demonstrate for the first time that a cytokine storm is associated with PFIB-induced ALI. Levels of 10 pro-inflammatory cytokines and one anti-inflammatory cytokine were significantly increased in lung tissues of PFIB-exposed mice. PFIB inhalation additionally led to significant oxidative stress in lung tissue. Inflammation-associated CD11b⁺Ly6G⁺Ly6C^int neutrophils and CD11b⁺Ly6G^-Ly6C^hi monocytes were significantly increased in blood in association with PFIB-induced ALI. Bcl-2/Bax-mediated lung cell apoptosis was significantly increased at 1?h, followed by a sustained decrease after 1?h, which was significant at 4–8?h in PFIB-exposed mice. This suppression of apoptosis is possibly associated with the Akt-signaling pathway.     

Diosmetin exerts cardioprotective effect on myocardial ischaemia injury in neonatal rats by decreasing oxidative stress and myocardial apoptosis

Myocardial injury caused by the myocardial ischaemia (MI) is still a troublesome condition in the clinic, including apoptosis, oxidative stress and inflammation. Diosmetin inhibits the cellular apoptosis and inflammatory response and enhances antioxidant activity. So, this study was designed to investigate the cardioprotective effects of diosmetin on MI model neonatal rats. Forty Sprague Dawley (SD) rats 7 days old were randomly divided into five groups. Four groups of rats received diosmetin (50, 100, and 200 mg/kg) or vehicle (MI group) after ischaemia. Another group received vehicle without ischaemia to serve as a control group. Rats were pretreated with diosmetin intraperitoneally for 7 days and intoxicated with isoproterenol (ISO, 85 mg/kg, sc) on the last 2 days. The expression of apoptotic molecules, myocardial systolic function index, antioxidant enzymes and myocardial enzyme was analyzed. Compared with the control group, the proliferation marker proteins of Ki67 were increased significantly (P < .05), the MI group significantly increased the cardiac apoptosis, oxidative stress and myocardial enzymes, and weakened myocardial contractility. The levels of p-P65/P65 were increased significantly (P < .05) with decreased p-AKT/AKT and p-Nrf2/Nrf2 (P < .05). Nevertheless, pretreatment with diosmetin reversed these changes, especially high-dose group. In summary, diosmetin has significant potential as a therapeutic intervention to ameliorate myocardial injury after MI and provides the rationale for further clinical studies.     

Chromium(III) oxide nanoparticles induced remarkable oxidative stress and apoptosis on culture cells

Chromium(III) oxide (Cr₂O₃) is used for industrial applications such as catalysts and pigments. In the classical form, namely the fine particle, Cr₂O₃ is insoluble and chemically stable. It is classified as a low‐toxicity chromium compound. Recently, industrial application of nanoparticles (a new form composed of small particles with a diameter of ≤100 nm, in at least one dimension) has been increasing. Cellular effects induced by Cr₂O₃ nanoparticles are not known. To shed light upon this, the release of soluble chromium from Cr₂O₃ nano‐ and fine‐particles in culture medium was compared. Fine Cr₂O₃ particles were insoluble in the culture medium; on the contrary, Cr₂O₃ nanoparticles released soluble hexavalent chromium into the culture medium. Cr₂O₃ nanoparticles showed severe cytotoxicity. The effect of Cr₂O₃ nanoparticles on cell viability was higher than that of fine particles. Cr₂O₃ nanoparticles showed cytotoxicity equal to that of hexavalent chromium (K₂Cr₂O₇). Human lung carcinoma A549 cells and human keratinocyte HaCaT cells showed an increase in intracellular reactive oxygen species (ROS) level and activation of antioxidant defense systems on exposure to Cr₂O₃ nanoparticles. Exposure of Cr₂O₃ nanoparticles led to caspase‐3 activation, showing that the decrease in cell viability by exposure to Cr₂O₃ nanoparticles was caused by apoptosis. Cellular responses were stronger in the Cr₂O₃ nanoparticles‐exposed cells than in fine Cr₂O₃‐ and CrCl₃‐exposed cells. Cellular uptake of Cr₂O₃ particles were observed in nano‐ and fine‐particles. The cellular influence of the extracellular soluble trivalent chromium was lower than that of Cr₂O₃ nanoparticles. Cr₂O₃ nanoparticles showed cytotoxicity by hexavalent chromium released at outside and inside of cells. The cellular influences of Cr₂O₃ nanoparticles matched those of hexavalent chromium. In conclusion, Cr₂O₃ nanoparticles have a high cytotoxic potential. © 2011 Wiley Periodicals, Inc. Environ Toxicol 2013.     

次氯酸介导的氧化应激及其病理生理学意义

机体内次氯酸(HClO)主要由髓过氧化物酶和血管过氧化物酶催化生成,HClO氧化性极强,基础水平的HClO在机体防御系统中起重要作用。然而,高浓度的HClO则给机体组织细胞造成氧化损伤。研究表明,HClO介导的氧化应激参与了动脉粥样硬化、细胞凋亡和衰老等多种病理生理过程。HClO可通过损害血管内皮功能、氧化修饰脂蛋白和增加斑块的不稳定性等多条途径促进动脉粥样硬化形成;通过影响线粒体渗透性转运孔和凋亡信号分子等途径促进细胞凋亡以及通过抑制抗衰老蛋白分子的表达和活性等途径促进细胞衰老。