回输的血小板在体内清除机制研究进展

生理学，病理学方面的研究发现血小板在体内清除主要发生在肝脏和脾脏，但衰老和损伤的血小板被体内清除系统识别和清除的机制还并不清楚。这一机制研究的深入将有助于解决血小板低温保存后体内存活期短．不能较长期发挥作用的难题，为血小板保存提出新的策略。本文就血小扳回输体内后的清除机制，包括P-选择蛋白，GPIbα及其受体Mac-1和内源性金属蛋白酶在血小板清除进程中的作用等的研究进展作一综述。     

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??OBJECTIVE To investigate the effect of verbascoside on iron deposition of astrocyte cell overexpressing heme oxygenase-1 gene, and to seek new drug in treating Alzheimer??s disease. METHODS Primary cultured astrocyte cells of rats were cultured and purified in vitro. With gene recombination and transfer techniques, transfect HO-1 gene into primary cultured astrocyte cells.HO-1 transfected astrocyte were then treated by different concentrations of verbascoside.Proliferation of cell was measured by CCK-8 assay and expression of HO-1 protein was analyzed by Western blotting. Iron deposition was also visualized by Perl??s Prussian blue stain. RESULTS Immunofluorescence staining showed that most of the cells were GFAP-postitive and the purity was over 95%. The expression of HO-1 protein was increased in HO-1 injury model of astrocyte. Treatment of verbascoside with variable concentration caused the decrease of HO-1 protein expression more or less and reduction of iron deposition in transfected cells(20 ??mol??L^-1reducing 47.69%,40 ??mol??L^-1 reducing 51.63%). CONCLUSION Verbascoside could enhance astrocyte cell resistance against injury induced by overexpression of heme oxygenase-1 gene.     

丹参胶囊在欧盟药品注册中的可读性测试研究和实践

药品说明书是载明药品信息的法定文件,对指导公众合理用药起着至关重要的作用。在欧美药品的申报体系和指南中,均要求申请者在药品上市前必须完成药品说明书可读性测试研究,以保证说明书内容通俗易懂,指导公众合理安全用药,避免用药不当可能导致的风险。由于审评理念和标准的差距,目前中国在新药评审的过程中缺乏药品说明书可读性测试研究的要求、法规和指南。以国内申报欧盟成功的品种丹参胶囊注册上市实践为案例,分析欧盟对于药品说明书可读性测试研究的要求,以期为我国建立和实施药品说明书可读性研究的管理思路提供借鉴和参考。     

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??OBJECTIVE To study the protective effect of donepezil on L-glutamic acid-induced injury and the effects on Na⁺ currents and NMDA receptor-mediated currents in neurons. METHODS Cortical and hippocampal neurons were isolated from postnatal 12 h Wistar rats and were cultured for 8-12 d. The protective effect of donepezil on L-glutamic acid-induced injury in neurons was investigated by MTT cell viability assay, and selective Na⁺ channel blocker TTX and selective NMDA receptor blocker MK-801 were taken as positive drugs. The effects of donepezil on Na⁺ and NMDA receptor-mediated current in hippocampal and cortical neurons was studied by using manual patch clamp. RESULTS Donepezil and MK-801 showed protective effects on L-glutamic acid-induced injury model, and TTX can slightly enhance the protective effect of MK-801. 1 ??mol??L^-1 donepezil slightly inhibited Na⁺ currents and NMDA receptor-mediated currents of hippocampal and cortical neurons and 10 ??mol??L^-1 donepezil showed obviously inhibiting effects on Na⁺ currents and NMDA receptor-mediated currents of hippocampal and cortical neurons. CONCLUSION Donepezil can protect neurons from glutamic acid damage, and its mechanism is related to inhibiting current of Na⁺ channel and NMDA receptor channel.     

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??OBJECTIVE To establish a new dissolution method of Ligustrazine Phosphate Pills, which provides reference for revising the quality standard. METHODS The dissolution media were hydrochloric acid solution(pH 1.2), acetate buffer solution(pH 4.5), phosphate buffer solution(pH 6.8) and water. The dissolution curves of six batches of Ligustrazine Phosphate Pills in the four kinds of dissolution media were compared to establish the dissolution method. Apparatus 2 was used for the new method of dissolution test,using 500 mL water as the dissolution medium,at the rate of 75 r??min^-1. The dissolution solution was taken at 20 min and analyzed by HPLC. The dissolution limit was set at 80%. RESULTS The dissolution curves of the six batches of samples were similar in the four kinds of dissolution media. The pills were dissolved completely within 15 min. CONCLUSION The determination method is highly reproducible, accurate and reliable, which can objectively reflect the dissolution of ligustrazine phosphate pills, and provides a basis for the reasonable unification and revision of the dissolution test of the current quality standard.     

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??OBJECTIVE To study the influence and mechanism of bioactive ingredients of Ligusticum chuanxiong Hort. on the transport of gastrodin based on cell culture model in vitro. METHODS Cell toxicity of gastrodin, ligustilide, senkyunolide ?? and senkyunolide A were detected by MTT assay. The transport mechanism of gastrodin and the influence of ligustilide, senkyunolide ?? and senkyunolide A on the transport of gastrodin were studied in MDCK-MDR1 monolayer cells. The changed expressions of P-gp caused by ligustilide, senkyunolide ?? and senkyunolide A were analyzed by Western blotting.RESULTS Gastrodin showed relatively poor absorption in MDCK-MDR1 cells for its apparent permeability coefficients were less than 1??10^-6 cm??s^-1. P-gp inhibitor made the P_app(B??A)/P_app(A??B) of gastrodin reduced from 1.29 to 0.79, which indicated that the transport of gastrodin was influenced by P-gp. In the presence of ligustilide(30 ??g??mL^-1) or senkyunolide ??(120 ??g??mL^-1), the P_app(A??B) of gastrodin in MDCK-MDR1 were significantly increased(P<0.01). In the presence of senkyunolide A(120 ??g??mL^-1), the P_app(A??B) of gastrodin in MDCK-MDR1 were markedly increased(P<0.05). High, medium and low dose of ligustilide, senkyunolide A and senkyunolide ?? could significantly inhibit the expression of P-gp protein.CONCLUSION The results indicate that the transport mechanism of gastrodin might be passive diffusion as the dominating process with the active transportation mediated mechanism involved. Ligustilide, senkyunolide A and senkyunolide ?? increase the transport of gastrodin attribute to down-regulate P-gp expression.     

二尖瓣关闭不全患者心脏瓣膜置换术后发生低心排综合征的相关因素及预测模型构建

目的:分析二尖瓣关闭不全(MR)患者心脏瓣膜置换术(CVR)后发生低心排综合征(LCOS)的相关因素,并构建预测模型.方法:选取我院2018年1月至2020年12月收治的163例MR患者作为研究对象,记录患者基线资料,均行CVR治疗,记录手术相关资料,统计LCOS发生情况,患者分为发生LCOS组和未发生LCOS组,比较两组基线资料及手术相关资料,经Logistic回归分析检验MR患者CVR后发生LCOS的风险因子,构建LCOS预测模型,采用Hosmer-Lemeshow拟合优度检验,并绘制ROC曲线,评价LCOS预测模型的预测效能.结果:163例MR患者完成CVR治疗后,28例发生LCOS,发生率为17.18％;发生LCOS组美国纽约心脏病学会(NYHA)分级、术前B型脑钠肽(BNP)、术前心肌肌钙蛋白T(cTnT)、水电解质紊乱占比高于未发生LCOS组,体外循环(CPB)时间、主动脉阻断(ACC)时间长于未发生LCOS组,术后出血量大于未发生LCOS组,术前LVEF低于未发生LCOS组(P<0.05);经Logistic回归分析结果显示,NHYA分级高、术前LVEF低、术前BNP高、术前cTnT高、水电解质紊乱、CPB时间长、ACC时间长、术后出血量大是MR患者CVR后LCOS发生的风险因子(OR>1,P<0.05);建立预测模型LCOS=0.951?NHYA分级(Ⅱ级=0,Ⅲ级=1)-0.179?术前LVEF+0.015?术前BNP+3.869?术前cTnT+1.014?水电解质紊乱(否=0,是=1)+0.084?CPB时间+0.129?ACC时间+0.298?术后出血量,预测风险值P=e(-17.813+LCOS)/[e(-17.813+LCOS)+1]?100％.绘制受试者工作曲线(ROC)曲线发现,LCOS预测模型用于预测MR患者CVR后LCOS发生风险的AUC为0.895,>0.80,有一定预测价值;LCOS预测模型经Hosmer-Lemeshow拟合优度检验χ2=3.324,P=0.912,P>0.05,模型矫正能力良好,拟合满意.结论:MR患者CVR后LCOS发生受多个风险因子影响,结合多个风险因子建立LCOS预测模型,对预测MR患者CVR后LCOS有一定效能.