摘要
BACKGROUND： As a non-invasive technique which can provide comprehensive biological information, 1H-magnetic resonance spectroscopy （1H-MRS） may provide valuable reference data for irreversible recovery or reversible changes in ischemic tissue after stroke. OBJECTIVE： To monitor and evaluate the effect of the urokinase thrombolytic therapy after experimental acute cerebral ischemia by 1H-MRS technology and investigate its adaptability. DESIGN： Randomly controlled animal study. SETTINGS： Shenzhen Hospital of Peking University and National Key Laboratory of Pattern and Atom ＆ Molecular Physics, Wuhan Physics and Mathematics Institute, Chinese Academy of Science. MATERIALS： Eleven healthy adult Sprague-Dawley （SD） rats, weighing 260–300 g and of both genders, were supplied by Experimental Animal Center of Tongji Medical Collage, Huazhong University of Science and Technology [SCXK （e） 2004-007]. 4.7T superconducting nuclear magnetic resonance meter was provided by Brucker Company. METHODS： The experiment was carried out in Shenzhen Hospital of Peking University and National Key Laboratory of Pattern and Atom ＆ Molecular Physics, Wuhan Physics and Mathematics Institute, Chinese Academy of Science from August 2003 to December 2005. ① The rats were randomly divided into 30-minute self-thrombo-embolism group （n =6） and 60-minute self-thrombo-embolism group （n =5）. Six rats in 30-minute self-thrombo-embolism group were occluded with clot embolus for 30 minutes and 5 rats in 60-minute self-thrombo-embolism group were occluded for 60 minutes. 10 000 U/kg urokinase was dissolved in 2 mL saline and the operation lasted for 5 minutes. ② 1H-MRS was performed before thrombolysis and at 3 hours and 24 hours after successful embolization. The metabolic changes of N-acetyl-L-aspartic acid （NAA）/phosphocreatine （PCr） ＋ creatine （Cr）, choline phosphate （Cho）/PCr＋Cr and lactic acid （Lac）/PCr＋Cr in the region of interests were analyzed. ③ The T2W image was conducted 24 hours after the thrombolytic therapy with TR=500 ms and TE=25 ms. ④ The subjects were sacrificed immediately after 1H-MRS and the brain tissues were cut into pieces and stained with HE method; in addition, pathological changes were observed under optic microscope. MAIN OUTCOME MEASURES： ① Metabolic changes of NAA/PCr＋Cr, Cho/PCr＋Cr and Lac/PCr＋Cr in the region of interests; ② T2W image at 24 hours after the thrombolysis; ③ pathological observation of brain tissue. RESULTS： Eleven rats were all involved in the final analysis. ① Metabolic changes in the region of interests ： In 30-minute self-thrombo-embolism group, the Lac peak emerged immediately after the embolism, but the ischemic zone decreased 3 hours after the thrombolytic therapy （0.252±0.01, 0.603±0.01, P 〈 0.01）. Lac/（PCr＋Cr） ratio was 0.290±0.01 at 24 hours after thrombolysis, which was higher than that at 3 hours after thrombolysis （P 〈 0.01）. The NAA/ （PCr＋Cr） ratio decreased significantly at 3 hours after the thrombolysis as compared with that before thrombolysis （0.922±0.16, 1.196±0.01, P 〈 0.05）. In 60-minute self-thrombo-embolism group, the Lac/（PCr＋Cr） ratio was higher at 3 hours after thrombolysis than that before thrombolysis （0.846±0.12, 0.601±0.11, P 〈 0.05） and the NAA/（PCr＋Cr） decreased at 3 hours after the embolism. Fluctuation of NAA/ （PCr＋Cr） ranged from 0.68 to 0.75 before thrombolysis and from 0.71 to 0.75 at 3 hours after thrombolysis. ② T2W image： T2W image showed that 2 subjects in 30-minute self-thrombo-embolism group whose Lac/NAA was higher than 0.7 suffered from intracranial hemorrhage. This meant that the subjects with Lac/NAA 〉 0.7 were more likely to suffer from intracranial hemorrhage. ③ Histological and morphological examinations： Optic microscope demonstrated that interspace surrounding nerve cells was widened at ischemic center; neurons were swelling; nucleus was stained lightly; pyknosis and mesenchymal edema were mainly observed in lateral cortex of brow and vertex and in lateralpart of corpus striatum. CONCLUSION： ①Compound parameters in ischemic area before thrombolysis should be regarded as an important predicting marker for thrombolytic therapy, effect evaluation and termination. ② 1H-MRS combining with other imaging technique is a detecting way for screening cases who are suitable for thrombolytic therapy.
BACKGROUND： As a non-invasive technique which can provide comprehensive biological information, 1H-magnetic resonance spectroscopy （1H-MRS） may provide valuable reference data for irreversible recovery or reversible changes in ischemic tissue after stroke. OBJECTIVE： To monitor and evaluate the effect of the urokinase thrombolytic therapy after experimental acute cerebral ischemia by 1H-MRS technology and investigate its adaptability. DESIGN： Randomly controlled animal study. SETTINGS： Shenzhen Hospital of Peking University and National Key Laboratory of Pattern and Atom ＆ Molecular Physics, Wuhan Physics and Mathematics Institute, Chinese Academy of Science. MATERIALS： Eleven healthy adult Sprague-Dawley （SD） rats, weighing 260–300 g and of both genders, were supplied by Experimental Animal Center of Tongji Medical Collage, Huazhong University of Science and Technology [SCXK （e） 2004-007]. 4.7T superconducting nuclear magnetic resonance meter was provided by Brucker Company. METHODS： The experiment was carried out in Shenzhen Hospital of Peking University and National Key Laboratory of Pattern and Atom ＆ Molecular Physics, Wuhan Physics and Mathematics Institute, Chinese Academy of Science from August 2003 to December 2005. ① The rats were randomly divided into 30-minute self-thrombo-embolism group （n =6） and 60-minute self-thrombo-embolism group （n =5）. Six rats in 30-minute self-thrombo-embolism group were occluded with clot embolus for 30 minutes and 5 rats in 60-minute self-thrombo-embolism group were occluded for 60 minutes. 10 000 U/kg urokinase was dissolved in 2 mL saline and the operation lasted for 5 minutes. ② 1H-MRS was performed before thrombolysis and at 3 hours and 24 hours after successful embolization. The metabolic changes of N-acetyl-L-aspartic acid （NAA）/phosphocreatine （PCr） ＋ creatine （Cr）, choline phosphate （Cho）/PCr＋Cr and lactic acid （Lac）/PCr＋Cr in the region of interests were analyzed. ③ The T2W image was conducted 24 hours after the thrombolytic therapy with TR=500 ms and TE=25 ms. ④ The subjects were sacrificed immediately after 1H-MRS and the brain tissues were cut into pieces and stained with HE method; in addition, pathological changes were observed under optic microscope. MAIN OUTCOME MEASURES： ① Metabolic changes of NAA/PCr＋Cr, Cho/PCr＋Cr and Lac/PCr＋Cr in the region of interests; ② T2W image at 24 hours after the thrombolysis; ③ pathological observation of brain tissue. RESULTS： Eleven rats were all involved in the final analysis. ① Metabolic changes in the region of interests ： In 30-minute self-thrombo-embolism group, the Lac peak emerged immediately after the embolism, but the ischemic zone decreased 3 hours after the thrombolytic therapy （0.252±0.01, 0.603±0.01, P 〈 0.01）. Lac/（PCr＋Cr） ratio was 0.290±0.01 at 24 hours after thrombolysis, which was higher than that at 3 hours after thrombolysis （P 〈 0.01）. The NAA/ （PCr＋Cr） ratio decreased significantly at 3 hours after the thrombolysis as compared with that before thrombolysis （0.922±0.16, 1.196±0.01, P 〈 0.05）. In 60-minute self-thrombo-embolism group, the Lac/（PCr＋Cr） ratio was higher at 3 hours after thrombolysis than that before thrombolysis （0.846±0.12, 0.601±0.11, P 〈 0.05） and the NAA/（PCr＋Cr） decreased at 3 hours after the embolism. Fluctuation of NAA/ （PCr＋Cr） ranged from 0.68 to 0.75 before thrombolysis and from 0.71 to 0.75 at 3 hours after thrombolysis. ② T2W image： T2W image showed that 2 subjects in 30-minute self-thrombo-embolism group whose Lac/NAA was higher than 0.7 suffered from intracranial hemorrhage. This meant that the subjects with Lac/NAA 〉 0.7 were more likely to suffer from intracranial hemorrhage. ③ Histological and morphological examinations： Optic microscope demonstrated that interspace surrounding nerve cells was widened at ischemic center; neurons were swelling; nucleus was stained lightly; pyknosis and mesenchymal edema were mainly observed in lateral cortex of brow and vertex and in lateralpart of corpus striatum. CONCLUSION： ①Compound parameters in ischemic area before thrombolysis should be regarded as an important predicting marker for thrombolytic therapy, effect evaluation and termination. ② 1H-MRS combining with other imaging technique is a detecting way for screening cases who are suitable for thrombolytic therapy.
基金
the Scientificand Technological ResearchProjects of Shenzhen, No.200404092
the Projects ofNational Key Laboratory ofthe Chinese Academy ofScience, No. T152301
