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探讨载促红细胞生成素的壳聚糖-硬脂酸(CS-SA)胶束给药系统对戊四唑诱导的小鼠癫痫的影响。小鼠给予载人重组促红细胞生成素的壳聚糖-硬脂酸(r-HuEPO-CS-SA)胶束制剂和r-HuEPO普通制剂24 h后,观察对戊四唑(PTZ)诱导的急性癫痫模型中发作潜伏时间、发作级别、大发作持续时间以及次数的影响。此外,小鼠隔天注射r-HuEPO-CS-SA胶束制剂和普通制剂,观察对PTZ诱导的癫痫形成过程的影响。结果:在PTZ急性模型中,给予r-HuEPO普通制剂仅4 000 IU/kg剂量组在降低发作级别、减少大发作持续时间和减少发作次数方面有显著差异(P<0.05)。而给予r-HuEPO-CSCS-SA胶束制剂2 000 IU/kg就可显著增加潜伏时间,降低大发作持续时间(P<0.05)。并且给予r-HuEPO-CS-SA胶束制剂4 000 IU/kg、8 000 IU/kg,在延长潜伏时间、降低发作级别、减少大发作持续时间和减少发作次数方面均有显著差异(P<0.05)。但在慢性癫痫点燃过程中,给予r-HuEPO-CS-SA胶束制剂和普通制剂均不能缓解癫痫形成的进程。本研究表明r-HuEPO-CS-SA胶束制剂可以显著缓解PTZ诱导的急性癫痫发作,作用较r-HuEPO普通制剂更明显,但对于PTZ诱导的癫痫形成过程无明显作用,提示载促红细胞生成素的CS-SA胶束给药系统有望更好的用于防治癫痫发作。
To investigate the effect of erythropoietin-loaded chitosan-stearic acid (CS-SA) micellar drug delivery system on pentylenetetrazole-induced seizures in mice. Mice were challenged with pentylenetetrazole (PTZ) for 24 h after administration of r-HuEPO-CS-SA micelles and r-HuEPO common formulations containing recombinant recombinant erythropoietin Acute epilepsy model seizure latency, seizure level, the duration of the major episodes and the number of impact. In addition, mice were injected with r-HuEPO-CS-SA micelles and common preparations every other day to observe the effect on PTZ-induced epilepsy. RESULTS: In the acute PTZ model, only a 4 000 IU / kg dose of r-HuEPO was given in a dose-dependent manner to reduce the level of seizures, reduce the duration of major seizures and reduce the number of seizures (P <0.05). However, administration of 2 000 IU / kg r-HuEPO-CSCS-SA micelles significantly increased latency and duration of major episodes (P <0.05). (4 000 IU / kg and 8 000 IU / kg) of r-HuEPO-CS-SA micelles were significantly different in prolonging the latency, reducing the severity of seizures, reducing the duration of major attacks and reducing the number of seizures (P < 0.05). However, neither r-HuEPO-CS-SA micelles nor common formulations were able to alleviate the progression of epilepsy during the ignition of chronic epilepsy. This study showed that r-HuEPO-CS-SA micellar preparation can significantly relieve PTZ-induced acute seizures, more obvious than r-HuEPO general preparations, but no significant effect on PTZ-induced epilepsy, suggesting that erythropoietin Sufficient CS-SA micelles delivery system is expected to be better for the prevention and treatment of seizures.