大黄酚三种制剂在脑缺血再灌注损伤小鼠的组织分布与药效学比较

摘要

目的：比较大黄酚聚氰基丙烯酸丁酯纳米囊、大黄酚羟丙基-β-环糊精包合物、大黄酚脂质体三种制剂与N,N-二甲基甲酰胺溶解的大黄酚,在脑缺血再灌注损伤小鼠各组织的分布及相关药效学作用.方法：采用小鼠脑缺血再灌注损伤模型,测定小鼠血、脑、心、肾、肝、脾、肺等组织中大黄酚含量,观察三种大黄酚制剂对脑组织内丙二醛(malondialdehyde,MDA)、单胺氧化酶-B(monoamine oxidase B,MAO-B)、一氧化氮(nitric oxide,NO)、一氧化氮合酶(nitric oxide synthase,NOS)、脂褐素(lipofuscin,LF)、乙酰胆碱酯酶(acetylcholin-esterase,AChE)活性和总氨基酸含量的影响,以及对心肌组织LF活性和海马形态学变化的影响.结果：各剂型大黄酚在小鼠体内分布浓度次序为：血>脑>肾>肝>心>脾>肺.大黄酚三种制剂10.0,1.0,0.1 mg·kg-1剂量,在脑组织及血、肝组织中的含量均高于N,N-二甲基甲酰胺溶解的大黄酚组(P<0.01或0.05),且呈剂量依赖性.并可不同程度改善脑缺血再灌注损伤引起的老化相关酶的活性和代谢产物含量的变化,改善海马的病理形态.结论：大黄酚三种制剂均可保护脑缺血再灌注损伤小鼠,增强大黄酚抗衰老药效,其作用机制可能与增加脑组织含量,调节老化相关酶的活性及改善海马的病理形态相关.%　　Objective:To compare the pharmacodynamics and the tissue distribution of chrysophanol loaded polybutylcyanoacrylate nanocapsules,chrysophanol-hydroxypropyl-β-cyclodextrin inclusion complex,chrysophanol liposomes and DMF dissolved chrysophanol in mice with cerebral ischemia reperfusion. Methods:Using the cerebral ischemia reperfusion in-jury model,determined the chrysophanol content in blood,brain,heart,kidney,liver,spleen,lung of mice;measured the activity of malondialdehyde (MDA),monoamine oxidase-B (MAO-B), nitric oxide (NO),nitric oxide synthase (NOS),lipofuscin (LF),acetylcholinesterase (AChE) in brain,the content of amino acid (AA) in brain and the content of lipofuscin (LF) in heart;observed the morphology of hippocampal. Results:The order of chrysophanol concentration in mouse tissues is:blood>brain>kidney>liver>heart>spleen>lung. Compared with chrysophanol DMF,chrysophanol concentrations of chrysophanol formulations (10.0,1.0,0.1 mg·kg-1 dose groups) in brain,liver and blood tissues were significantly high (P<0.01 or 0.05) in a dose-depen-dent manner. At the same time,the aging-related enzymes’ activity and the pathological morphol-ogy in hippocampal area were improved to some extent. Conclusion:All the three chrysophanol formulations could enhance the anti-aging effects of chrysophanol in mice with cerebral ischemia reperfusion,with the possible mechanisms involving enhancement of chrysophanol content in brain,regulation of the activity of aging-related enzymes and improvement of the pathological morphology in hippocampi area.