低频超声控释尿激酶缓释系统在大鼠脑出血中的应用研究

目的研究载尿激酶Pluronic P-105(the urokinase loaded in Pluronic P-105,NP-UK)缓释系统在活体内的控释情况及其对脑出血的治疗效果。方法制作大鼠脑出血模型,分别用NP-UK和尿激酶注入血肿腔,用低频超声激发,测定脑组织尿激酶含量、脑组织含水量,进行行为学评分、观察脑组织病理学变化。结果NP-UK非超声组大鼠尿激酶含量缓慢降低,NP-UK超声组大鼠在超声后即刻尿激酶浓度较高,24 h后迅速降低;尿激酶组中尿激酶含量在术后即刻浓度较高,24 h后迅速降低。NP-UK超声组脑组织含水量高峰提前至24 h,且峰值明显降低。行为学评价各组无统计学意义。病理学NP-UK超声组脑水肿程度最轻。结论NP-UK缓释系统在体内是可以利用低频超声满意控释的,并且其溶解颅内血肿的效果比单纯尿激酶要确切。

APPLICATION STUDY OF THE UROKINASE EXTENDED-RELEASE SYSTEM CONTROLLED WITH LOW-FREQUENCY ULTRASOUND IN EXPERIMENTAL INTRACEREBRAL HEMORRHAGE IN RATS

Objective To study the releasing effect of the urokinase loaded in Pluronic P-105(NP-UK) extended-release dosage system controlled with low-frequency ultrasound and its therapeutic efficacy on intracerebral hemorrhage(ICH).Methods Quantitative fresh autologous artery blood was infused into caudate nucleus to build up rat ICH model,urokinase(UK) and NP-UK were infused with stereotactic guidance into the hematoma.Then the low-frequency ultrasound was used to activate the UK release.UK content of brain tissue and brain water content were detected,behavioral tests and histopathologic observation were also done.Results UK concentration in brain tissue without US activating in NP-UK group exhibited a mild decreasing tendency,which remain a little high concentration 72 hours later,but that with US activating exhibited a rather high concentration immediately after activating and appeared a rapid decreasing tendency 24 hours later;that of UK group exhibited a high concentration immediately after operation and low concentration 24 hours later(P<0.05).Brain water content showed that the peak of brain edema in NP-UK group appeared 24 hours after infusing NP-UK of which was also lower than other groups(P<0.05).Behavioral tests showed no significant difference among each group(P>0.05).Histopathologic observation showed that brain edema of the NPUK group was the weakest.Conclusion The NP-UK extended-release dosage system can well release under the control of low-frequency ultrasound and which has more significant efficiency than the common UK in hematoma lysis.