沙棘提取物对老龄小鼠的抗氧化作用

目的评价沙棘提取物的抗氧化作用。方法采用老龄小鼠模型,设置老龄对照组、溶剂对照组和0.50g/kg BW、1.00g/kg BW、1.50g/kg BW沙棘提取物组,干预30 d后检测各组动物血液丙二醛(MDA)含量和谷胱甘肽过氧化物酶(GSHPX)活性,肝脏谷胱甘肽(GSH)和蛋白质羰基含量。结果与对照组比较,各剂量组10%肝匀浆中蛋白质羰基含量差异无显著性,1.50g/kg BW沙棘提取物组溶血液中MDA含量降低(P<0.05)、GSH-PX活性明显升高(P<0.05)、10%肝匀浆中GSH含量明显升高(P<0.05)。结论在本试验条件下,沙棘提取物能提高老龄小鼠的抗氧化能力。     

Inhibition of DNA-dependent protein kinase catalytic subunit by small molecule inhibitor NU7026 sensitizes human leukemic K562 cells to benzene metabolite-induced apoptosis

Benzene is an established leukotoxin and leukemogen in humans. We have previously re- ported that exposure of workers to benzene and to benzene metabolite hydroquinone in cultured cells induced DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to mediate the cellular response to DNA double strand break (DSB) caused by DNA-damaging metabolites. In this study, we used a new, small molecule, a selective inhibitor of DNA-PKcs, 2-(morpholin-4-yl)-benzo[h]chomen-4-one (NU7026), as a probe to analyze the molecular events and pathways in hydroquinone-induced DNA DSB repair and apoptosis. Inhibition of DNA-PKcs by NU7026 markedly potentiated the apoptotic and growth inhibitory effects of hydroquinone in proerythroid leukemic K562 cells in a dose-dependent manner. Treatment with NU7026 did not alter the production of reactive oxygen species and oxidative stress by hydroquinone but repressed the protein level of DNA-PKcs and blocked the induction of the kinase mRNA and protein expression by hydroquinone. Moreover, hydroquinone increased the phos- phorylation of Akt to activate Akt, whereas co-treatment with NU7026 prevented the activation of Akt by hydroquinone. Lastly, hydroquinone and NU7026 exhibited synergistic effects on promoting apop- tosis by increasing the protein levels of pro-apoptotic proteins Bax and caspase-3 but decreasing the protein expression of anti-apoptotic protein Bcl-2. Taken together, the findings reveal a central role of DNA-PKcs in hydroquinone-induced hematotoxicity in which it coordinates DNA DSB repair, cell cycle progression, and apoptosis to regulate the response to hydroquinone-induced DNA damage.     

红景天西洋参合剂提高小鼠缺氧耐受力及其机制

目的探讨红景天西洋参合剂提取物对小鼠耐缺氧的影响及相关机制。方法采用常压耐缺氧实验、亚硝酸钠中毒存活实验、急性脑缺血性缺氧实验并进行全血分析。每个实验,昆明雄性小鼠随机分为低、中、高剂量组（n=12）,给药剂量分别为0．6、1．2、1．8g／kg·BW,相当于推荐剂量的10倍、20倍、30倍,设对照组（n=12）。各剂量组均给予20ml／kg·BW的受试物,每日一次,连续30d,同时对照组给予相同容量的生理盐水。全血分析探讨其可能机制。结果各剂量组均延长常压耐缺氧条件下小鼠的存活时间,呈剂量一效应关系;高剂量组小鼠存活时间比对照组延长23．39％,差异有统计学意义（P〈0．05）;亚硝酸钠中毒存活实验中,高剂量组与对照组相比较,存活时间延长46．12％,差异有统计学意义（P〈0．05）;各剂量组显著性延长急性脑缺血性缺氧小鼠的喘息时间,差异极有统计学意义（P〈0．01）;各组小鼠红细胞数量、血红蛋白含量均无明显改变,差异无统计学意义（P〉0．05）。结论红景天西洋参合剂提取物具有显著提高动物的耐缺氧能力,可能是通过降低机体整体或局部器官的氧消耗实现的。     

联苯双酯固体脂质纳米粒注射给药在大鼠体内的药动学

目的:研究联苯双酯固体脂质纳米粒在大鼠体内的药动学。方法:制备联苯双酯固体脂质纳米粒,大鼠尾静脉注射给药,高效液相色谱法测定不同时间血浆中联苯双酯的浓度,通过3P97程序计算药动学参数。结果:药动学研究表明联苯双酯固体脂质纳米粒消除较慢,生物利用度较高,无论是药物溶液还是纳米混悬液,在大鼠体内的药动学过程均符合二室模型。结论:与药物溶液相比,联苯双酯固体脂质纳米粒具有明显的缓释效果,同时还能提高药物的生物利用度。