药物与肾脏

肾脏既是药物的作用点,又是排泄药物的重要器官。其血流量按单位组织重量计算,远大于脑、肝和甲状腺。因此,药物及其代谢产物同肾脏接触机会很多。其中某些药物在与肾脏长期接触或在肾组织中蓄积到一定     

Protective effects and mechanism of total coptis alkaloids on A β25–35 induced learning and memory dysfunction in rats

Objective: To observe the effect of total coptis alkaloids (TCA) on β-amyloid peptide (Aβ25-35) induced learning and memory dysfunction in rats, and to explore its mechanism. Methods: Forty male Wistar rats were randomly divided into four groups: the control group, the model group, the TCA low dose (60 mg/kg) group and the TCA high dose (120 mg/kg) group, 10 in each. Aβ25-35 (5μl, 2μg/μl) was injected into bilateral hippocampi of each rat to induce learning and memory dysfunction. TCA were administered through intragavage for consecutive 15 days. Morris Water Maze test was used to assess the impairment of learning and memory; concentration of malondialdehyde (MDA) in cerebral cortex was determined by thiobarbituric acid reactive substance to indicate the level of lipid peroxidation in brain tissues; activity of manganese-superoxide dismutase (Mn-SOD) in cerebral cortex was determined by xanthine-oxidase to indicate the activity of the enzyme; and NF-κB protein expression in cerebral cortex was measured by SP immunohistochemistry. Results: (1) Morris Water Maze test showed that, during the 4 consecutive days of acquisition trials, the rats in the model group took longer latency and searching distance than those in the control group (P<0.01), which could be shortened by high dose TCA (P<0.05); during the spatial probe trial on the fifth day, the rats in the model group took shorter searching time and distance on the previous flat area than those in the control group (P<0.01), which could be prolonged after TCA treatment (for low dose group, P<0.05; for high dose group, P<0.01). (2) Analysis of cerebral cortical tissues showed that, compared with the control group, MDA level got significantly increased and Mn-SOD activity decreased in the model group (both P<0.01). After having been treated with TCA, the MDA level got significantly decreased (P<0.05 and P<0.01 respectively for low and high dose group), while relative increase of Mn-SOD activity only appeared in high dose group (P<0.05). (3) Immunohistochemistry analysis showed the protein expression of NF-κB got significantly increased after modeling, while high dose TCA can significantly inhibit it. Conclusion: TCA could improve Aβ25-35 induced dysfunction of learning and memory in rats, and its protective mechanism is associated with its actions in decreasing MDA level, increasing Mn-SOD activity and inhibiting the expression of NF-κB in cerebral cortex.     

构建院系教学督导运行模式的探索与实践

教学督导是深化高校管理体制改革、构建高校教学质量监控体系的重要一环。院系一级督导是当前督导工作中的薄弱环节，值得研究和探讨。督导工作运行模式是指教学督导过程中的运作方式系统。本文结合药学院教学督导实践，提出五个结合的院系督导工作运行模式，对于规范院系督导工作、提高督导质量具有重要意义。     

单胺氧化酶B——治疗神经元退行性变的可能靶点

单胺氧化酶B(MAOB)是一类黄素依赖性蛋白酶,由520个氨基酸构成,通过C端的跨膜螺旋结合于线粒体外膜。MAOB基因定位于X染色体,核心启动子位于-246/-99。MAOB基因表达受多种因素调控。MAOB在多巴胺代谢途径中发挥重要作用。可将多巴胺降解为二羟苯乙酸,并生成过氧化氢。MAOB基因敲除小鼠对神经毒素1-甲基-4-苯基-1,2,3,6-四羟嘧啶(MPTP)具有耐受性。MAOB分布于脑内特定脑区,在多种神经元退行性疾病中发现脑内MAOB活性升高。MAOB可能发挥着调节氧化应激、参与神经元退行性变等作用。     

铝过负荷致小鼠神经退行性变与氧化应激和抗氧化应激系统关系的研究

目的：研究铝过负荷致小鼠神经元退行性变与脑内氧化应激系统和抗氧化应激系统之间的关系。方法：采用氯化铝溶液（相当于400mg／kg Al^3＋）灌胃小鼠,每天1次,1周6天,连续3月,建立铝过负荷所致小鼠神经元退行性变模型。以被动回避性学习记忆能力和空间识别能力的改变、大脑皮层和海马总SOD、SOD2活性和MDA含量变化、以及海马病理学改变为观察指标。结果：铝过负荷能明显导致小鼠进行性被动回避性学习记忆和空间识别能力障碍;出现海马神经元核固缩和神经元丢失;脑组织总SOD和SOD2活性及MDA含量呈平行变化,出现先升高后降低趋势,但各时点SOD和SOD2活性及MDA含量均明显高于对照组。结论：铝过负荷明显致小鼠神经元退行性变,学习记忆能力下降。其机制可能与铝负荷引起脑内氧化应激反应和抗氧化应激系统动员失恒有关。     

克拉霉素的体内抗菌作用

克拉霉素对金黄色葡萄球菌、肺炎球菌和乙型溶血性链球菌感染小鼠有明显的治疗作用,其作用强度按等效剂量算,比红霉素强5～11.7倍,而对大肠杆菌、肺炎杆菌感染治疗无效.     

汉防已碱和钩藤碱的促递质释放作用和钙调蛋白活性抑制作用

鉴于汉防已碱和钩藤碱都有钙拮抗作用,而近来报道多种钙拮抗剂均有促进递质释放作用,因此我们用预先摄取[~3H]-7-NE的大鼠输精管测定了此二生物碱对递质释放的作用.结果表明,两生物碱均有极强的促递质释放作用.按药物作用5min促递质释放量占组织总量的百分率计算,汉防已碱10~(-6)M为9.53±5.27%(M±SD,以下同),10~(-5)M为     

人PPARαLBD融合蛋白表达质粒的构建和诱导条件优化

过氧化物酶体增殖物活化受体α(Peroxisome prolifterator- activated receptor α,PPARα)属于Ⅱ型核受体,通过其配体结合区(1igand binding domain,LBD)结合特定的激动剂对参与机体代谢的关键酶、受体等的表达起调节作用.本研究以人肝组织总RNA为模板,利用RT-PCR方法扩增出人PPARαLBD基因的cDNA片段,将其插入表达载体pMAL-p2X的麦芽糖结合蛋白(Maltose binding protein,MBP)编码基因malE的下游,转化入宿主菌E. coli.TB1.然后对重组质粒在大肠杆菌TB1中的表达条件进行了优化.经SDS-PAGE分析和Bio-Rad Quantity One凝胶影像分析结果表明,诱导剂IPTG的浓度为0.4 mmol/L,30℃振荡诱导培养6 h时,可获得高效表达的MBP-PPARαLBD融合蛋白,重组蛋白的表达量可达胞质总蛋白的31.34%.为进一步纯化和PPARα配体筛选研究打下了良好的基础.     

杜仲叶醇提取物对大鼠血管内皮细胞的保护作用

目的探讨杜仲叶醇提取物(Alcohol extractive of Folium Eucommiae,AEFE)对动脉粥样硬化(AS)大鼠血管内皮细胞的保护作用。方法复制实验性大鼠AS模型,AEFE(70、140和420 mg.kg-1.d-1,ig)给药6 w,实验结束时测定血浆一氧化氮(NO)、内皮素-1(ET-1)、血栓素B2(TXB2)和6酮--前列腺素F1α(6-K-PGF1α)的含量;取主动脉和冠状动脉进行形态学观察。结果AEFE 140和420 mg.kg-1.d-1可明显升高AS模型大鼠血浆中NO、ET-1和6-Keto-PGF1α浓度(P<0.01),而对TXB2无影响;明显减轻AS大鼠主动脉和冠状动脉内皮细胞的缺失,但两组间无显著差异。结论AEFE具有维持NO/ET和TXA2/PGI2平衡、保护血管内皮细胞结构和功能的作用。