Aim To evaluate the time-effect and dose-effect of prasugrel hydrobromide acetic acid compound （PHAAC） inhibiting platelet aggregation. Methods For the time-effect study, 190 Sprague-Dawley （SD） rats were devided ...Aim To evaluate the time-effect and dose-effect of prasugrel hydrobromide acetic acid compound （PHAAC） inhibiting platelet aggregation. Methods For the time-effect study, 190 Sprague-Dawley （SD） rats were devided into 19 groups （n- 10）： the vehicle control group, the PHAAC groups （0.5, 1, 2, 4, 6, 24, 48, 72, 96 h） and the prasugrel hydrochloride groups （0.5, 1, 2, 4, 6, 24, 48, 72, 96 h）. Rats were singly intra- gastic administration of the vehicle, the PHAAC （5 mg·kg^-1） or the prasugrel hydrochloride （5 mg · kg^-1 ）, re- spectively. Blood samples were taken at each time point for the determination of platelet aggregation rate （PAR）. For the dose-effect study, 110 SD rats were devided into 11 groups （n= 10）： the vehicle control group, the PHAAC groups （10, 5, 2.5, 1, 0.5 mg · kg^-1, dosage of prasugrel） and the prasugrel hydrochloride groups （ 10, 5, 2.5, 1, 0.5 mg · kg^-1, dosage of prasugrel） . Blood samples were taken at 4 h after drug administration for the determination of PAR. Results Compared with the vehicle group, PHAAC has significant anti-platelet ag- gregative effects （P 〈 0.05） at the time of 0.5, 1, 2, 4, 6, 24, 48 h, and the effect at the time of 4 h was the strongest. There were no obvious differences between the effect of PHAAC （5 mg · kg^-1） and prasugrel hydrochlo- ride （5 mg · kg^-1） at each time point. Compared with the vehicle group, intragastic administration of PHAAC at the doses of 10, 5, 2.5, 1, 0.5 mg · kg^-1 could obviously inhibite the platelet aggregation, and showed a dose- dependent manner. There were no significant differences between the effect of PHAAC and prasugrel hydrochloride at the same dose. Conclusion PHAAC can inhibit platelet aggregation in a dose-dependent manner, and the effect at 4 h after drug administration is the strongest. The action strength and duration of PHAAC are similar with that of the prasugrel hydrochloride.展开更多
Many clinical studies have addressed the treatment of acute cerebral hemorrhage using acupuncture. However, few studies have examined the relationship between time of acupuncture and curative effect on cerebral hemorr...Many clinical studies have addressed the treatment of acute cerebral hemorrhage using acupuncture. However, few studies have examined the relationship between time of acupuncture and curative effect on cerebral hemorrhage. By observing the effect of acupuncture on changes in histopathology, ultrastructure, and neuroethology in a cerebral hemorrhage model of rats, we have directly examined the time-effect relationship of acupuncture. The rat model of cerebral hemorrhage was produced by slowly injecting autologous blood to the right caudate nucleus. The experimental groups were: 3-, 9-, 24-, and 48-hour model groups; and 3-, 9-, 24-, and 48-hour acupuncture groups. The sham-operation group was used for comparison. Acupuncture was performed at the Neiguan(PC6) and Renzhong(DU26) acupoints, twice a day, 6 hours apart, for 5 consecutive days. Brain tissue changes were observed by light microscopy and transmission electron microscopy. Neuroethology was assessed using Bederson and Longa scores. Our results show that compared with the sham-operation and model groups, Bederson and Longa scores were lower in each acupuncture group, with visibly improved histopathology and brain tissue ultrastructure. Further, the results were better in the 3-and 9-hour acupuncture groups than the 24-and 48-hour acupuncture groups. Our findings show that acupuncture treatment can relieve pathological and ultrastructural deterioration and neurological impairment caused by the acute phase of cerebral hemorrhage, and may protect brain tissue during this period. In addition, earlier acupuncture intervention following cerebral hemorrhage(by 3 or 9 hours) is associated with a better treatment outcome.展开更多
背景:活性氧可能与肌腱病发生、发展密切相关,但其确切作用及相关信号转导机制尚未进行全面总结。目的:综述目前临床或临床前原始研究,对活性氧在肌腱病中的作用及相关信号转导通路进行归纳总结,探究其作用特点以及是否存在统一的下游...背景:活性氧可能与肌腱病发生、发展密切相关,但其确切作用及相关信号转导机制尚未进行全面总结。目的:综述目前临床或临床前原始研究,对活性氧在肌腱病中的作用及相关信号转导通路进行归纳总结,探究其作用特点以及是否存在统一的下游通路。方法:通过计算机对PubMed、Embase、Web of Science以及中国知网、万方、维普数据库中的相关原始研究进行检索,依据入选标准对检索结果进行筛选、排除,最终纳入90篇文献进行综述分析。结果与结论:①活性氧可通过同时作用于肌腱细胞和细胞外基质来影响肌腱愈合方向,其作用方式呈双面作用特点,浓度可能是决定其作用方向的关键,低剂量活性氧可以参与肌腱正常生理愈合活动或肌腱组织具有刺激自适应性可能是产生这种作用特点的内在机制。②活性氧主要是通过基质金属蛋白酶、丝裂原活化蛋白激酶、线粒体凋亡、叉头转录因子O家族、自噬、炎症以及抗氧化信号转导通路,来改变肌腱细胞外基质的组成和结构,影响肌腱细胞正常修复、应对外界和维持生存能力,对肌腱状态造成影响。③不同的活性氧刺激强度、时间以及外在环境可能会造成下游分子通路的不同改变,从而对肌腱产生不同影响。④由于目前纳入的活性氧正、负面作用的考察文献数量差距较大,可能对寻找活性氧在肌腱中作用特点的背后因素造成一定的分析误差;另外由于大多数实验干预条件和关注结果比较单一,具体活性氧的时效、量效机制以及与其他干预因素的协同作用未能明确,也未能构建活性氧在肌腱病中的分子作用整体体系。⑤文章结果表明,活性氧未来或许可以作为一种有利因素参与肌腱病的治疗和预防,并促进之后肌腱病中氧化应激信号转导通路和整体分子作用体系的探索,也为不同抗氧化剂在肌腱病中的治疗策略打下研究基础,以更好地达到防治肌腱损伤变性的目的。展开更多
文摘Aim To evaluate the time-effect and dose-effect of prasugrel hydrobromide acetic acid compound （PHAAC） inhibiting platelet aggregation. Methods For the time-effect study, 190 Sprague-Dawley （SD） rats were devided into 19 groups （n- 10）： the vehicle control group, the PHAAC groups （0.5, 1, 2, 4, 6, 24, 48, 72, 96 h） and the prasugrel hydrochloride groups （0.5, 1, 2, 4, 6, 24, 48, 72, 96 h）. Rats were singly intra- gastic administration of the vehicle, the PHAAC （5 mg·kg^-1） or the prasugrel hydrochloride （5 mg · kg^-1 ）, re- spectively. Blood samples were taken at each time point for the determination of platelet aggregation rate （PAR）. For the dose-effect study, 110 SD rats were devided into 11 groups （n= 10）： the vehicle control group, the PHAAC groups （10, 5, 2.5, 1, 0.5 mg · kg^-1, dosage of prasugrel） and the prasugrel hydrochloride groups （ 10, 5, 2.5, 1, 0.5 mg · kg^-1, dosage of prasugrel） . Blood samples were taken at 4 h after drug administration for the determination of PAR. Results Compared with the vehicle group, PHAAC has significant anti-platelet ag- gregative effects （P 〈 0.05） at the time of 0.5, 1, 2, 4, 6, 24, 48 h, and the effect at the time of 4 h was the strongest. There were no obvious differences between the effect of PHAAC （5 mg · kg^-1） and prasugrel hydrochlo- ride （5 mg · kg^-1） at each time point. Compared with the vehicle group, intragastic administration of PHAAC at the doses of 10, 5, 2.5, 1, 0.5 mg · kg^-1 could obviously inhibite the platelet aggregation, and showed a dose- dependent manner. There were no significant differences between the effect of PHAAC and prasugrel hydrochloride at the same dose. Conclusion PHAAC can inhibit platelet aggregation in a dose-dependent manner, and the effect at 4 h after drug administration is the strongest. The action strength and duration of PHAAC are similar with that of the prasugrel hydrochloride.
基金supported by a grant from the Tianjin Science and Technology Commission,China,No.05YFSZSF02600(to PL)
文摘Many clinical studies have addressed the treatment of acute cerebral hemorrhage using acupuncture. However, few studies have examined the relationship between time of acupuncture and curative effect on cerebral hemorrhage. By observing the effect of acupuncture on changes in histopathology, ultrastructure, and neuroethology in a cerebral hemorrhage model of rats, we have directly examined the time-effect relationship of acupuncture. The rat model of cerebral hemorrhage was produced by slowly injecting autologous blood to the right caudate nucleus. The experimental groups were: 3-, 9-, 24-, and 48-hour model groups; and 3-, 9-, 24-, and 48-hour acupuncture groups. The sham-operation group was used for comparison. Acupuncture was performed at the Neiguan(PC6) and Renzhong(DU26) acupoints, twice a day, 6 hours apart, for 5 consecutive days. Brain tissue changes were observed by light microscopy and transmission electron microscopy. Neuroethology was assessed using Bederson and Longa scores. Our results show that compared with the sham-operation and model groups, Bederson and Longa scores were lower in each acupuncture group, with visibly improved histopathology and brain tissue ultrastructure. Further, the results were better in the 3-and 9-hour acupuncture groups than the 24-and 48-hour acupuncture groups. Our findings show that acupuncture treatment can relieve pathological and ultrastructural deterioration and neurological impairment caused by the acute phase of cerebral hemorrhage, and may protect brain tissue during this period. In addition, earlier acupuncture intervention following cerebral hemorrhage(by 3 or 9 hours) is associated with a better treatment outcome.
文摘通过健康信息传播和教育说服公众形成健康行为意愿是一个现实课题。本文以精细加工可能性模型(elabo‐ration likelihood model,ELM)为理论基础,将说服路径分为中心路径和外围路径,同时引入短期的时间纵向数据追踪。本文实施了10天左右持续使用健康信息的日记报告实验,基于30名大学生提交的377条健康信息日记数据,建立个体层面与信息线索、时间层面的多层线性回归模型(hierarchical linear modeling,HLM),探究健康信息对个体健康行为意愿的说服机制。研究结果表明,健康行为意愿的说服过程主要是信息质量和来源可信度的混合式说服路径;在7天周期内,健康信息说服效果逐渐增强,其中信息质量的说服效果更为稳定,来源可信度的说服效果则随着时间推移逐渐被抵消;健康信息说服路径随个体特征和接触时机而变;健康意识调节来源可信度和信息热度对说服效果的影响,且具有时间效应;卷入度调节信息质量和来源可信度对信息说服效果的影响,但不存在时间效应。本文的研究结果有助于深入理解健康信息对健康行为意愿改变的说服机制,为建立“以人为本”的个性化健康信息传播和健康教育方案提供了参考。
文摘目的:探讨“冬病夏治”全方配伍和无白芥子配伍延胡索乙素在模型家兔“肺俞”穴皮下药代动力学特征及药代动力学-药效动力学(PK-PD)模型的相关性。方法:支气管哮喘模型家兔随机分成延胡索单方组、缺白芥子组、全方组,微透析技术收集14 h穴位皮下透析液,液相色谱-质谱法(Liquid Chromatography Mass Spectrometry,LCMS)法检测方中君药延胡索主要成分延胡索乙素浓度,获得药代动力学参数;酶联免疫吸附试验(ELISA)法检测对应时间点模型动物血清中IgE水平,获得药效学参数;对药动学、药效学参数进行PK-PD模型拟合。结果:白芥子配伍后的药峰浓度(C_(max))、药时曲线下面积(AUC_(0-t))、平均滞留时间(MRT_(0-t))均显著增加(P<0.01,P<0.01,P<0.05),达峰时间(T_(max))提前(P<0.01);“浓度-时间-效应”三维曲线表明,方中有白芥子配伍时,药效出现更快、消退更慢,起效时间晚于峰浓度,具有一定滞后性。结论:动力学参数、PK-PD模型结果表明,白芥子配伍能够改变“方中君药”——延胡索的主要成分延胡索乙素穴位局部的皮下分布,促进方中君药有效成分快速吸收,延长滞留时间,在方剂中起到主药、改善其他药物分布的“双重”作用。
文摘背景:活性氧可能与肌腱病发生、发展密切相关,但其确切作用及相关信号转导机制尚未进行全面总结。目的:综述目前临床或临床前原始研究,对活性氧在肌腱病中的作用及相关信号转导通路进行归纳总结,探究其作用特点以及是否存在统一的下游通路。方法:通过计算机对PubMed、Embase、Web of Science以及中国知网、万方、维普数据库中的相关原始研究进行检索,依据入选标准对检索结果进行筛选、排除,最终纳入90篇文献进行综述分析。结果与结论:①活性氧可通过同时作用于肌腱细胞和细胞外基质来影响肌腱愈合方向,其作用方式呈双面作用特点,浓度可能是决定其作用方向的关键,低剂量活性氧可以参与肌腱正常生理愈合活动或肌腱组织具有刺激自适应性可能是产生这种作用特点的内在机制。②活性氧主要是通过基质金属蛋白酶、丝裂原活化蛋白激酶、线粒体凋亡、叉头转录因子O家族、自噬、炎症以及抗氧化信号转导通路,来改变肌腱细胞外基质的组成和结构,影响肌腱细胞正常修复、应对外界和维持生存能力,对肌腱状态造成影响。③不同的活性氧刺激强度、时间以及外在环境可能会造成下游分子通路的不同改变,从而对肌腱产生不同影响。④由于目前纳入的活性氧正、负面作用的考察文献数量差距较大,可能对寻找活性氧在肌腱中作用特点的背后因素造成一定的分析误差;另外由于大多数实验干预条件和关注结果比较单一,具体活性氧的时效、量效机制以及与其他干预因素的协同作用未能明确,也未能构建活性氧在肌腱病中的分子作用整体体系。⑤文章结果表明,活性氧未来或许可以作为一种有利因素参与肌腱病的治疗和预防,并促进之后肌腱病中氧化应激信号转导通路和整体分子作用体系的探索,也为不同抗氧化剂在肌腱病中的治疗策略打下研究基础,以更好地达到防治肌腱损伤变性的目的。
