摘要
目的尝试人体白蛋白、硫酸镁与溶栓联合应用延长脑缺血溶栓治疗时间窗的可能性和可靠性。方法利用线栓法建立SD大鼠大脑中动脉阻塞(MCAO)模型。对建立的MCAO模型按照神经功能损害评分标准进行评分,对评分≥3,应用随机数据表法进行随机分组:A组为缺血3h后溶栓(8只);B组为缺血6h后溶栓(8只);C组为缺血3h后神经保护药物干预后溶栓(8只);D组为缺血6h后神经保护药物干预后溶栓(8只)。溶栓治疗是在脑缺血的不同时间把线栓拔出后以尿激酶2500u稀释后自股静脉缓慢注入。神经保护药物干预,即在线栓拔出前0.5h,将5%硫酸镁溶液,按照500mgkg体重的用量自腹腔注射;然后再自股静脉缓慢注入20%人体白蛋白2ml,15min内注射完。分别对脑缺血MCAO模型3h或6h治疗前、治疗后3h、治疗后2d和9d分别行MRI检查。在DWI和T2WI图像上观测梗死灶的变化,T2WI图像上测量梗死灶大小,采用PWI测量梗死中心区(即DWI上高信号中心,gs)、梗死边缘区(DWI上高信号边缘)、皮质区(pz)的血流动力学变化。重点测量相对脑血流量(rCBV)、信号强度时间曲线的相对上升斜率(rMSI)。最后一次MRI检查结束后行病理检查,免疫组化检测MMP2的表达、激光扫描共聚焦显微镜检查(LCMS)。结果B组溶栓后,DWI上高信号中心(gs)、pz及pbra区的rCBV均有进一步的提高。gs区的升高,达对侧的240%,同时伴有gs区的rMSI进一步下降,提示gs的过度灌注,伴有对比剂的大量漏出。与脑缺血3h溶栓治疗后相比,差异有显著性(P<0.05)。D组治疗后3h,gs、pbra区的rCBV稍下降,pz区rCBV稍升高,与B组相比,差异无显著性(P>0.05);gs和pz区rMSI缓慢上升,pbra区缓慢下降,与B组相比,差异无显著性(P>0.05)。D组治疗后9d随访,gs、和pz区的rCBV降低,pbra区的rCBV稍降低,与D组治疗后3h相比,差异无显著性意义(P>0.05);gs、pbra区和pz区rMSI于治疗后9d缩短至对侧的40%～60%,与治疗后3h相比,
Objective To identify whether albumin and magnesium sulfate combining with thrombolysis could prolong thrombolytic time window. Methods The intraluminal MCA filament model was used to produce focal MCAO. The rats experienced 3hs ischemia with receiving scores ≥3 were randomly divided into four groups. Magnesium sulfate injection （500 mg/kg）, 20% albumin （2 ml） and urokinase （2500 unit） were injected through abdominal cavity or femoral vein respectively with filament withdrew after 3hs or 6hs ischemia. All rats were undergone MRI before thrombolysis and 3hour, 2day and 9day after the thrombolysis respectively. After the last MRI examination, the rats of each sub-group were performed histopathology, immunocheministry and LSCM for the control study. Results Thrombolysis combining with albumin, lowered the hematocrit, raised plasma colloid oncotic pressure, raised the rCBV at gs.pz and pbra areas as well as rMSI at gs area（ P 〈 0.05 ）. As a result the leakage of BBB reduced, and no hemorrhage transformation occurred even after onset of 6 hs ischemia treated with urokinase. Histopathology revealed neurological score improvement in thrombolysis combining with magnesium sulfate group. MMP-2 expression decreased at gs and pbra areas after thrombolysis combining with albumin. Conclusions Albumin and magnesium sulfate combining with thrombolysis could prolong thrombolytic time window.
出处
《介入放射学杂志》
CSCD
2005年第5期510-515,共6页
Journal of Interventional Radiology
基金
国家自然科学基金项目(30470506)
上海市科委重点资助项目(03411985)
上海市医学重点学科基金项目(05Ⅲ023)
上海市博士后基金(2003)
