Inhibitory effects of grape seed proanthocyanidin extract on selenite-induced cataract formation and possible mechanism

This study investigated the inhibitory effect of grape seed proanthocyanidin extract(GSPE) on selenite-induced cataract formation in rats and the possible mechanism.Eighty 8-day-old Sprague-Dawley rats were divided randomly into 5 groups:control group,model group,three GSPE groups(low dose,medium dose and high dose).Control group received subcutaneous injection of physiological saline.Model group was given subcutaneous injection of sodium selenite(20 μmol/kg body weight) on the postpartum day 10,and once every other day for consecutive three times thereafter.GSPE treated groups were respectively administered GSPE at doses of 50,100,and 200 mg/kg body weight intragastrically 2 days prior to the selenite injection(that was,on the postpartum day 8),and once daily for fourteen consecutive days thereafter.The opacity of lenses was observed,graded and photographed under the slit lamp microscopy and the maximal diameter of the nuclear cataract plaques was measured.The lenses were analyzed for superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-PX),malondialdehyde(MDA),calcium(Ca 2+),nitric oxide(NO) and anti-hydroxyl radical ability(anti-OH).The histomorphology of lenses was observed with HE staining under a light microscope.The levels of calpainⅡ,and iNOS protein and mRNA expression in lenses were detected by using immunohistochemistry and real-time quantitative RT-PCR.The results showed subcutaneous injection of sodium selenite led to severe nuclear cataract in model group,and the achievement ratio of model group was 100%.As compared with model group,the degree of lenses opacity and the maximal diameter of nuclear cataract plaques were significantly reduced in GSPE-treated groups.Moreover,we observed selenite treatment caused a significant decrease in the activities of antioxidative enzymes(SOD,CAT,GSH-PX) and anti-OH ability,accompanied by a significant increase in the levels of MDA,NO,Ca 2+ as well as iNOS,and calpainⅡ protein and mRNA expression.Administration of GSPE could dose-dependently pre     

Hepatoprotective activity of the ethanol extract of Sarcopyramis Nepalensis

The present study examined the protective effect of the ethanol extract of Sarcopyramis nepalensis (EESN) on agents-induced hepatotoxicity in mice and the possible mechanism. Acute liver injury was induced by administration of either CCl4 or D-GalN. The animals were divided into 5 groups in terms of different treatment: normal group, CCl4 or D-GalN group, silymarin or bifendate group, low dose EESN group (10 mg/kg) and high dose EESN group (30 mg/kg). Liver function was evaluated by detecting the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The oxidize stress markers were measured, including malondialdehyde (MDA), glutathione peroxidase (GSH) and superoxide dismutase (SOD). Liver tissues were histopathologically examined by hematoxy-lin-eosin (H&E) staining. The acute toxicity study revealed that there was no toxicity of EESN at the dose of 5 g/kg in mice. The levels of ALT and AST in serum, and the MDA level in live tissues were significantly increased and the activities of SOD and GSH substantially decreased in mice after CCl4 or D-GalN treatment. These biochemical and oxidize stress markers were profoundly improved after treatment with EESN at different doses, which was similar to the results of silymarin or bifendate treatment. The histophathological examination revealed the significant improvement in the pathological changes of the liver in EESN-treated mice as compared to those in CCl4 or D-GalN group. It was concluded that EESN possesses potential antioxidant and hepatoprotective properties and has therapeutic potential for liver diseases.     

Acute and Sub-chronic Toxicity of Tetrandrine in Intravenously Exposed Female BALB/c Mice

Objective: To evaluate the acute and sub-chronic toxicity of intravenously administered tetrandrine(TET) in female BALB/c mice. Methods: The median lethal dose(LD_(50)) of intravenously administered TET was calculated in mice using Dixon's up-and-down method. In the acute toxicity study, mice were intravenously administered with TET at a single dose of 20, 100, 180, 260 and 340 mg/kg, respectively and were evaluated at 14 days after administration. In the sub-acute toxicity study, mice were intravenously administered various doses of TET(30, 90 and 150 mg/kg) each day for 14 consecutive days. Clinical symptoms, mortality, body weight, serum biochemistry, organ weight and histopathology were examined at the end of the experiment, as well as after a 1-week recovery period. Result: LD_(50) was found to be 444.67±35.76 mg/kg. In the acute toxicity study, no statistically significant differences in body weight, blood biochemistry, or organ histology were observed between the administration and control groups when mice were intravenously administered with single dose at 20, 100, 180, 260 and 340 mg/kg of TET(P0.05). In the sub-acute toxicity study, no significant changes in body weight, biochemistry and organ histology were observed with up to 90 mg/kg of TET compared with the control group(P0.05), however, in the 150 mg/kg administered group, TET induced transient toxicity to liver, lungs and kidneys, but withdrawal of TET can lead to reversal of the pathological conditions. Conclusions: The overall findings of this study indicate that TET is relatively non-toxic from a single dose of 20, 100, 180, 260 or 340 mg/kg, and that up to 90 mg/kg daily for 14 consecutive days can be considered a safe application dose.     

Di-（n-butyl）-phthalate-induced Oxidative Stress and Depression-like Behavior in Mice with or without Ovalbumin Immunization

Objective To investigate the relationship between atopic allergy and depression and the role of DBP in the development of depression. Methods BALB/c mice were randomly divided into eight groups: saline; ovalbumin(OVA)-immunized; saline+DBP(0.45 mg/kg·d); saline+DBP(45 mg/kg·d); DBP(0.45 mg/kg·d) OVA-immunized; DBP(45 mg/kg·d) OVA-immunized; saline+hydrocortisone(30 mg/kg·d); and hydrocortisone(30 mg/kg·d)-exposed OVA-immunized. Behavior(e.g. open-field, tail suspension, and forced swimming tests), viscera coefficients(brain and spleen), oxidative damage [e.g. reactive oxygen species(ROS), malondialdehyde(MDA), and glutathione(GSH)], as well as levels of IgE and IL-4, were then analyzed. Results In the saline and OVA groups, the degree of depression symptoms in mice increased with increasing DBP concentration. Additionally, the OVA-immunity groups were associated with more serious depressive behavior compared with the same exposure concentration in the saline group. Oxidative damage was associated with a dose-dependent increase in DBP in the different groups. IL-4 and IgE levels were associated with low-dose DBP stimulation, which changed to high-dose inhibition with increasing DBP exposure, possibly due to spleen injury seen at high DBP concentrations. Conclusion Development of an atopic allergy has the potential to increase the risk of depression in mice, and it seems that DBP helps OVA to exert its effect in our present model. Moreover, the results of our study implicate a certain connection between brain oxidative stress and depression, which deserves a further exploration.     

Toxicological Assessment of Trans-resveratrol

Objective To evaluate toxicity and safety of trans-resveratrol (t-RSV). Methods For assays of acute toxicity, genetic toxicity, and sub-chronic toxicity, Ames test, mice bone marrow erythrocyte micronucleus, and mice sperm abnormality were performed. Results In the acute oral toxicity tests, maximum tolerable dose (15 g/kg) in male and female Kunming mice showed no toxicological signs. For 90-d feeding of t-RSV at dosage range of 167–500 mg/(kg?d) in both male and female Sprague-Dawley rats, no noticeable toxicological effects were observed. Conclusion T-RSV has no acute toxicity and no genotoxicity, no harmful effects on the human body at the tested dosage range and thus resveratrol is safe for human consumption.     

Toxic Effects of Atrazine on Reproductive System of Male Rats

Objective This study was designed to evaluate the toxic effects of Atrazine （ATZ） on the reproductive system of male rats. 〈br〉 Methods Male Sprague-Dawley rats were exposed to ATZ by gavage at dosages of 0, 38.5, 77, and 154 mg/kg bw/day for 30 d. The toxic effects of ATZ to rats were assessed through histopathologcal observation, spermatozoa quality evaluation, testicular marker enzyme indicators, antioxidant capacity and reproductive hormone levels. Results Significant adverse effects on reproductive system were observed in rats exposed to ATZ at different dosages compared with 0 mg/kg group, including an irregular and disordered arrangement of the seminiferous epithelium in 154 mg/kg group;a decreased spermatozoa number and an increased spermatozoa abnormality rate in 77 and 154 mg/kg groups;decreased levels of acid phosphatase （ACP）, alkaline phosphatase （AKP）, lactic dehydrogenase （LDH）, and succinate dehydrogenase （SDH） with the increasing of ATZ concentration; a decreased level of total antioxidant capacity （TAC） in a dose-dependent manner, and a decreased reduced glutathione （GSH） level and an increased malondialdehyde （MDA） content in 154 mg/kg group;and decreased serum levels of testosterone （T） and inhibin-B （INH-B） and an increased serum level of follicle stimulating hormone （FSH） in 77 and 154 mg/kg groups, and an increased serum level of luteinizing hormone （LH） in 154 mg/kg group. Conclusion These results suggested that relatively high doses of ATZ could exert reproductive toxicity of male rats.     

Anti-breast cancer properties and toxicity of Dillenia suffruticosa root aqueous extract in BALB/c mice

Objective:To determine the anti-breast cancer activities and the safety oral consumption of Dillenia suffruticosa root aqueous extract(DRAE)in BALB/c mice.Methods:In the anti-breast cancer study,female BALB/c mice were divided into five groups(n=12),which were(1)positive control(with breast cancer,untreated),(2)negative control(without breast cancer,untreated)and other three groups of mice with breast cancer treated with 1 000,500 and 250 mg/kg of DRAE,respectively,by oral gavage for 28 days.All mice except from the negative control group were injected into the mammary fat pad with 4T1 cells(1×1054T1 cells/0.1 m L of phosphate buffer solution).DRAE was administered orally on Day 11 after the tumor has developed.Results:The tumor volume of the 1 000 mg/kg of DRAE group reduced significantly compared to the positive control while treatment with 500 mg/kg of DRAE had significantly inhibited metastasis to the heart.In the acute toxicity study,treatment with up to5 000 mg/kg of DRAE was not toxic to the animals,indicating its safety when a large amount of this plant extract was ingested.Based on the sub-acute toxicity study,treatment of the highest dose of DRAE(1 000 mg/kg)had mild liver toxicity indicated by mild focal hemorrhage.Conclusions:DRAE possesses anti-breast cancer properties but at the same time it shows mild toxicity to the liver.The non observable adverse effect dose for DRAE is500 mg/kg.     

The protective effect of ascorbic acid and thiamine supplementation against damage caused by lead in the testes of mice

Lead is a ubiquitous environmental and industrial pollutant that may have toxic effects on the male. Vitamins may protect against toxic effects of lead in the liver and reproductive system, which is confirmed by our initial research. The aim of this study was to further investigate the protective effects of vitamins （ascorbic acid combined with thiamine） on lead acetate （Pb）-induced reproductive toxicities in mice and study the possible mechanisms underlying these effects. Forty-five male mice were randomly divided into 3 groups, 15 mice in each and received daily intragastric administration with control, Pb （20 mg/kg）, and Pb＋vitamins （ascorbic acid of 420 mg/kg＋thiamine of 30 mg/kg） for 6 weeks, respectively. The Pb-treated animals showed significant decreases in the epididymal sperm count and motility compared to the control group, while the Pb＋vitamins group had significant increases for these variables. Moreover, an increasing apoptosis of germinal cells induced by Pb was reduced by vitamin treatment. Pb induced the activation of Caspase-3, Fas/Fas-L and Bcl-2 with elevated levels, and the adaptor protein primarily regulated signaling through Fas and required for Fas-induced apoptosis. In conclusion, ascorbic acid combined with thiamine exhibited protective effect on reproductive system by inhibiting Pb-induced excessive cell apoptosis.     

Effects of Parental Dietary Exposure to GMRice TT51 on the Male Reproductive System of Rat Off spring

ObjectiveTo evaluatethehealth effects of parental dietary exposure to GM rice TT51 on the male reproductive system of rat offspring.
MethodsRice-based diets, containing 60% ordinary grocery rice, MingHui63, or TT51 by weight, were given to parental rats (15 males/30 females each group) for 70 days prior mating and throughout pregnancy and lactation. After weaning, eightmale offspringratswere randomly selected at each group and fed with dietscorrespondent to their parents’ for 70 days. The effects of exposure to TT51 on male reproductive system of offspring rats were assessed through sperm parameters, testicular function enzyme activities, serumhormones (FSH, LH, and testosterone levels), testis histopathological examination, and the relativeexpression levels of selected genes along the hypothalamic-pituitary-testicular (HPT) axis.
ResultsNo significant differences were observed in body weight, food intake, organ/body weights, serum hormone, sperm parameters, testis function enzyme ACP, LDH, and SDH activities, testis histopathological changes, and relative mRNA expression levels of GnRH-R, FSH-R, LH-R, and AR along the HPT axis.
ConclusionThe resultsof this studydemonstrate that parental dietary exposure to TT51 reveals no significant differences on the reproductive system of male offspring rats compared with MingHui63 and control.     

In vivo and in vitro effects of QHF combined with chemotherapy on hepatocellular carcinoma

Objective： To investigate the synergistic anti-tumor effect of QHF （a Chinese medicine formula with anti- tumor active ingredients, including 800 mg/kg Cinobufotalin, 14 mg/kg Ginsenoside Rg3, 5.5 mg/kg Notoginseng and 100 mg/kg Lentinan） when combined with the chemotherapy drug cisplatin （DDP）. Methods： Hepatocellular carcinoma H22 cells were implanted into mice and after the transplants were successfully established the animals were divided into four groups, namely a normal saline（NS） control group, QHF group, DDP group and QHF＋DDP group. The tumor growth was monitored and the survival time determined. In vitro studies employing H22 cells used the first three groups, and determined the effects of QHF and DDP on tumor cell cycle distribution, apoptosis and morphologic changes in vitro. Results： QHF significantly inhibited the growth of tumors and prolonged the survival time of mice with hepatocellular carcinomas. QHF combined with DDP could attenuate DDP-induced leucopenia, spleen and thymus atrophy and other indicators of toxicity. The inhibition rate of tumor growth reached 82.54% with QHF＋DDP, and QHF prolonged the life span of DDP-treated mice by 66.83%. In the in vitro experiments tumor cells showed morphological changes characteristic of apoptosis by both light and transmission electron microscopy in the QHF group, and the apoptosis rate was 33.85%. Moreover, the proportion of cells in the G0/G1 phase was increased and those in the S-phase decreased. Conclusion： QHF combined with DDP could significantly inhibit tumor growth, induce the apoptosis of tumor cells and effectively attenuate DDP toxicity.     

Prevention of H2O2 Induced Oxidative Damages of Rat Testis by Thymus algeriensis

ObjectiveWe evaluate the effects ofThymus algeriensis (TEO) against hydrogen peroxide (H2O2) toxicity on body and testis weight, testis sperm count, testis lipid peroxidation, and antioxidant enzyme activities in rats.
MethodsRats were treated with low (LD) and high dose (HD) of H2O2 (0.1 and 1 mmol/L) in the presence or absence of TEO (150 mg/kg).
ResultsThe results exhibited a significant decrease in body weight and testis weight, in total sperm number decrease (P<0.05), sperm motility and percentage of sperm viability, leading to complete arrest, in sperm flagellar beat frequency by the gavage of 1 mmol/L H2O2 compared to controls.The administration of H2O2 resulted in a significant reduction in testis GSH, GPx, CAT, SOD, and GST activity andsignificant increase (P<0.05) in MDAconcentration compared with the untreated control animals. TEO pre-treatment protected testis from the H2O2generated oxidative stress.These results were confirmed byhistological architecture examinations.
ConclusionH2O2 has the ability to alter the sperm function, characteristics and development of testis. However, TEO is an efficient natural agent, which can prevent the testis from H2O2-induced oxidative damage in rats.     

马尾松针提取物调控Nrf2-ARE通路治疗雄激素性脱发的研究

目的 观察马尾松针提取物对双氢睾酮(Dihydrotestosterone,DHT)诱导的雄激素性脱发(Androgenetic alopecia,AGA)模型小鼠的干预效应,并通过核因子E2相关因子2(Nrf2)-抗氧化反应元件(ARE)信号通路探讨马尾松针提取物促毛发生长的作用机制.方法 采用DHT皮下注射建立AG...     

苯与甲醛联合染毒对小鼠睾丸及精子的损伤作用

目的 通过研究苯与甲醛联合染毒对雄性小鼠睾丸及精子的损伤情况,探讨苯与甲醛联合对其损伤的作用机制。 方法 选择40只SPF级成年雄性小鼠随机分为4组,分别为对照组(A组)、苯单独染毒组(B组)、甲醛单独染毒组(C组)、苯与甲醛联合染毒组(D组),每组小鼠10只。A组小鼠灌胃生理盐水和植物油;B组灌胃200 mg/(kg.bw)剂量的苯;C组灌胃10 mg/(kg.bw)剂量的甲醛、D组灌胃苯200 mg/(kg.bw)+甲醛10 mg/(kg.bw)。各组均连续染毒5 d,再饲养30 d后称重处死动物,分离双侧睾丸测定其睾丸脏器系数、光学显微镜下观察小鼠精子数量、死亡精子和畸形精子;按照常规方法制作睾丸组织病理切片,HE染色后置显微镜下观察其睾丸组织病理变化;采用试剂盒检测睾丸T-AOC和Na+-K+-ATP酶活性;采用SPSS 17.0软件对实验数据进行统计分析。 结果 D组小鼠体重及睾丸脏器系数均分别低于A、B、C组(P<0.05);与A及B、C组比较,D组小鼠精子数减少[14.9/(107个·g附睾)],精子的死亡率(45.17‰)、畸形率(58.33‰)均增加(P<0.05);B、C、D三个染毒组小鼠睾丸组织均出现不同程度病理损害,其中D组病理损害明显;D组小鼠睾丸T-AOC、Na+-K+-ATP活性较B、C组降低,差异均有统计学意义(P<0.05)。 结论 甲醛与苯联合染毒对小鼠睾丸及精子有明显损伤作用;其损伤机制可能通过抑制ATP酶活性降低睾丸生殖细胞的抗氧化性有关。      

阿托伐他汀通过Nrf2/HO-1改善慢性心力衰竭大鼠心功能的作用及机制研究

目的 研究阿托伐他汀通过核因子 E2相关因子2(Nrf2)/血红素氧合酶-1(HO-1)改善慢性心力衰竭(CHF)大鼠心功能的作用及机制研究。方法 将成年SPF级雄性SD大鼠随机分为假手术(SHAM)组、CHF组、阿托伐他汀组、二甲基亚砜(DMSO)+SHAM组、DMSO+CHF组、DMSO+阿托伐他汀组、Nrf2抑制剂(ML385)+阿托伐他汀组,每组各8只大鼠。采用腹主动脉缩窄法建立CHF模型或进行假手术操作,造模后给予10 mg/kg阿托伐他汀、30 mg/kg Nrf2抑制剂ML385或等体积的DMSO溶剂灌胃干预。给药8周后采用超声仪检测各组大鼠心功能参数左室射血分数(LVEF)、左室短轴缩短率(LVFS)、左心室舒张末期内径(LVEDD),左心室收缩末期内径(LVESD),观察心脏大体形态并检测心脏质量、心脏体质量比,取左心室心肌组织检测丙二醛(MDA)、8-羟基脱氧鸟嘌呤(8-OHdG)、总抗氧化力(T-AOC)的水平及Nrf2、HO-1的表达。结果 腹主动脉缩窄法造模后,CHF组的LVEDD、LVESD、心脏质量、心脏体质量比及心肌中MDA、8-OHdG的水平均高于SHAM组,LVEF、LVFS、心肌中T-AOC水平及Nrf2、HO-1表达水平均低于SHAM组(P<0.05);经阿托伐他汀干预后,阿托伐他汀组的LVEDD、LVESD、心脏质量、心脏体质量比及心肌中MDA、8-OHdG的水平均低于CHF组,LVEF、LVFS、心肌中T-AOC水平及Nrf2、HO-1表达水平均高于CHF组(P<0.05);阿托伐他汀干预的同时给予Nrf2抑制剂ML385,ML385+阿托伐他汀组的LVEDD、LVESD、心脏质量、心脏体质量比及心肌中MDA、8-OHdG的水平均高于DMSO+阿托伐他汀组,LVEF、LVFS、心肌中T-AOC水平及Nrf2、HO-1表达水平均低于DMSO+阿托伐他汀组(P<0.05)。结论 阿托伐他汀对CHF大鼠的心功能具有改善作用,这一作用可能与激活Nrf2/HO-1通路、减轻氧化应激反应有关。     

芹菜素对雄性小鼠肝脏组织总抗氧化能力、还原型谷胱甘肽/氧化型谷胱甘肽值、丙二醛含量影响研究

目的观察不同剂量、不同作用时间芹菜素对雄性小鼠肝脏总抗氧化能力（T-AOC）、还原型谷胱甘肽/氧化型谷胱甘肽（GSH/GSSG）、丙二醛（MDA）含量的影响。方法 200只成年SPF级昆明种雄性小鼠随机分为对照组（生理盐水10 mL/kg）、低剂量组（芹菜素252 mg/kg）、中剂量组（芹菜素504 mg/kg）和高剂量组（芹菜素1008 mg/kg）。连续灌胃7、14、21、28、35 d,分批处死,称取肝脏制备匀浆,测定T-AOC、GSH、GSSG及MDA含量。结果高剂量组T-AOC含量[（1.397±0.641）U/mg]显著低于对照组[（1.573±0.781）U/mg]（P=0.000）;芹菜素灌胃28 d GSH/GSSG值相对对照组升高幅度最大（140.556%）;高剂量组灌胃21 d MDA含量[（1.068±0.729）nmol/mg]显著高于对照组[（0.354±0.212）nmol/mg]（P=0.000）。结论 1008 mg/kg芹菜素对小鼠肝脏组织T-AOC具有一定的抑制作用,并可增加肝脏脂质过氧化程度。T-AOC可以比较早地反映出机体抗氧化能力的变化。     

异绿原酸B对四氯化碳致小鼠急性肝损伤的保护作用

目的 研究异绿原酸B(ICAB)对四氯化碳(CCl4)致小鼠急性肝损伤的保护作用.方法 建立CCl4诱导小鼠急性肝损伤实验模型并评价ICAB的保护作用,测定小鼠血清丙氨酸转氨酶(ALT)、天冬氨酸氨基转移酶(AST)水平和肝组织丙二醛(MDA)含量,以及超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)的活性.采用HE染色对肝组织细胞形态进行观察;Western印迹法测定ICAB对肝损伤小鼠肝细胞中核因子E2相关因子2(Nrf2)、血红素氧合酶-1(HO-1)和醌氧化物还原酶1(NQO1)表达的影响.结果 ICAB各给药组(5、10和20 mg/kg)均可不同程度抑制CCl4所致小鼠血清ALT、AST和MDA的升高(P<0.01),ICAB高剂量组(20 mg/kg)明显提高肝细胞中SOD(P<0.01)和GSH-Px活性水平(P<0.05),降低MDA含量.同时,ICAB能改善CCl4造成的肝组织病理学损伤.此外,ICAB可促进Nrf2的表达及Nrf2的核转位,进而促进Nrf2下游靶蛋白HO-1和NQO1的表达.结论 ICAB对CCl4引起的小鼠急性肝损伤具有明显的保肝降酶作用,其作用机制可能与参与调节Nrf2信号通路、缓解氧化应激相关.     

miR-155/BACH1信号通路在三氧化二砷诱导肺腺癌细胞死亡中的机制研究

目的 探讨微小RNA 155（miR-155）、BTB 和 CNC 同源蛋白1 （BACH1）、醌氧化还原酶1（NQO1）和血红素氧合酶-1（HO-1）在三氧化二砷（ATO）诱导细胞死亡过程中的变化规律,以及miR-155和BACH1可能的调控关系,为增敏ATO治疗新靶点的发现奠定实验基础。方法 以不同浓度ATO处理肺腺癌A549细胞后,采用MTT实验检测细胞的存活率或死亡率,试剂盒检测细胞的总抗氧化能力,Westom blot检测BACH1、NQO1和HO-1蛋白的表达,实时荧光定量PCR(qRT-PCR)检测miR-155的表达水平。miR-155类似物（mimic）及其阴性对照转染对数期A549细胞,并设未转染组为对照,qRT-PCR检测miR-155表达水平后,以20 μmol/L ATO处理24 h,再进行MTT及Western blot检测。结果 10~100 μmol/L的ATO可降低细胞的存活率;与空白对照组相比,10、20 μmol/L的ATO可减弱细胞的总抗氧化能力,激活BACH1蛋白的表达,抑制miR-155以及NQO1和HO-1蛋白的表达;在转染miR-155 mimic后,20 μmol/L ATO处理后的A549细胞死亡率低于未转染组和转染阴性对照组,且ATO对BACH1蛋白的激活作用减弱,NQO1和HO-1蛋白表达则高于后两组（ P<0.05)。结论 ATO可通过抑制miR-155的表达,激活BACH1蛋白,抑制NQO1和HO-1蛋白的表达,从而削弱细胞的总抗氧化能力,最终诱导细胞死亡,提示miR-155和BACH1可作为ATO治疗肺癌过程中的增敏靶点。     

蒿甲醚对血吸虫抗氧化功能的影响

目的：观察蒿甲醚对小鼠体内日本血吸虫抗氧化功能的影响。方法：小鼠感染血吸虫尾蚴4-5周后，1次灌服蒿甲醚300mg/kg，并于治疗24h后剖杀，收集血吸虫合抱虫，测定其超氧化物岐化酶(SOD)、谷胱甘肽．S-转移酶(GST)和谷胱甘肽还原酶(CR)活力以及总抗氧化能力(T-AOC)、还原型谷胱甘肽(GSH)、维生素C(VitC)、维生素E(VitE)和巯基(thiol)水平。结果：体内经蒿甲醚作用24h后，虫体的SOD活力及T—AOC、thiol、VitC水平显下降，而CSH水平及CR活力则显升高。结论：蒿甲醚干扰血吸虫的抗氧化功能，使其易受氧自由基的攻击。     

异氟烷预处理激活Nrf2-ARE通路保护H9c2心肌细胞缺氧-复氧损伤

目的 研究异氟烷预处理对大鼠胚胎心肌细胞(H9c2)缺氧-复氧损伤及Nrf2-ARE信号通路的影响.方法 用大鼠H9c2细胞低氧模拟缺血性损伤,并将细胞分为空白对照组、缺氧-复氧组、异氟烷预处理组、转染Nrf2 siRNA组、转染非特异性siRNA组(Scramble组)、异氟烷预处理的Scramble组和异氟烷预处理的siRNA组.采用MTT法检测H9c2细胞存活率,TUNEL染色检测细胞凋亡,分别使用硫代巴比妥酸法(TBA)和分光光度法测定MDA和GSH水平,qRT-PCR及Western blot检测Nrf2、HO-1和NQO1基因的表达.结果 与空白对照组比较,缺氧-复氧组细胞活力降低,凋亡细胞数上升,MDA水平升高,GSH水平降低,同时H9c2细胞中Nrf2、HO-1和NQO1的mRNA和蛋白表达降低,差异均具有统计学意义(JP＜0.01).与缺氧-复氧组比较,异氟烷可提高H9c2细胞活力,降低凋亡细胞数,并降低MDA水平,升高GSH水平,上调Nrf2、HO-1和NQO1的表达(P＜0.05).siRNA转染组Nrf2的mRNA和蛋白表达与缺氧-复氧组和Scramble组相比均降低(P＜0.05),2％异氟烷对siRNA转染组Nrf2 mRNA和蛋白表达均无影响(P＞0.05);经2％异氟烷处理的siRNA转染组H9c2细胞存活率与空白对照组、2％异氟烷处理组和2％异氟烷处理的Scramble组相比降低,凋亡细胞数增多,MDA水平升高,GSH水平降低(P＜0.05).结论 异氟烷预处理对H9c2细胞缺氧-复氧损伤具有保护作用,这种保护作用与激活Nrf2-ARE信号通路有关.     

丙泊酚对人胃癌裸鼠移植瘤生长的影响

目的 探讨丙泊酚对人胃癌裸鼠移植瘤生长的影响,及其可能的作用机制。方法 培养人胃癌 细胞株SGC7901,复制裸鼠移植瘤模型30 只,随机分为对照组、生理盐水组和丙泊酚组,每组10 只。对照 组未做任何处理;生理盐水组腹腔注射生理盐水1.5 ml/kg ;丙泊酚组腹腔注射丙泊酚20 mg/kg,1 次/d,连 续2 周。观察各组裸鼠给药前后一般情况的变化,给药后每3 d 用游标卡尺测量移植瘤的长径和短径,计算移 植瘤体积。第15 天时将裸鼠脱臼处死,剥离瘤体。采用实时荧光定量聚合酶链反应和Western blot 检测各组 裸鼠移植瘤组织中核因子E2 相关因子2（Nrf2）、NAD（P）H 醌氧化还原酶1（NQO1）、血红素加氧酶-1 （HO-1）、B 淋巴细胞瘤（Bcl-2）、Bcl-2 相关X 蛋白（Bax）基因和蛋白的表达。结果 丙泊酚组裸鼠给药 后3、6、9、12 和15 d 的移植瘤体积小于对照组和生理盐水组（P <0.05）。与对照组和生理盐水组相比,丙 泊酚组裸鼠移植瘤体质量降低,而抑瘤率升高（P <0.05）。与对照组和生理盐水组相比,丙泊酚组裸鼠移植瘤 组织中Nrf2、NQO1、HO-1、Bcl-2 mRNA 和蛋白相对表达量降低,而Bax mRNA 和蛋白相对表达量升高 （P <0.05）。结论 丙泊酚可抑制人胃癌裸鼠移植瘤的生长,其机制可能与抑制Nrf2/ARE 信号通路,从而促 进细胞凋亡有关。