CAJ | 학술논문

目的观察低频超声联合尿激酶静脉溶栓治疗大鼠脑梗死的疗效和基质金属蛋白酶9（matrix metal oproteinase-9，MMP-9）及其抑制物1（tissue inhibitor of metal oproteinase-1，TIMP-1）在脑梗死溶栓治疗后的表达。 　　方法应用血栓栓塞法制备Wistar大鼠脑梗死模型160只，随机分为尿激酶治疗组、低频超声治疗组、低频超声联合尿激酶治疗组和对照组。进行神经功能缺损评分（Neurological Severity Score，NSS）并测定脑梗死体积，免疫组化观测MMP-9和TIMP-1的表达。 　　结果治疗前NSS评分尿激酶治疗组（9.09±1.33）、低频超声治疗组（9.16±1.23）、低频超声联合尿激酶治疗组（9.11±1.45）和对照组（9.28±1.14）比较差异无显著性（F=0.04，P＝0.99），治疗后NSS评分尿激酶治疗组（6.38±1.11）、低频超声治疗组（7.37±1.35）和低频超声联合尿激酶治疗组（5.08±1.31）均低于治疗前（t分别为4.95、3.10和6.52，P均＜0.01）。治疗后梗死灶体积尿激酶治疗组[（59.24±8.25）mm3]、低频超声治疗组[（76.36±9.48）mm3]、低频超声联合尿激酶治疗组[（56.01±9.77）mm3]均低于对照组[（94.90±11.09）mm3]（F=34.06，q=11.63、6.04、12.68；P均＜0.01）。根据治疗方法不同分为尿激酶治疗组和非尿激酶治疗组，两组大鼠脑出血发生率分别为20％、3.75％（校正χ2=8.60，P＜0.01）；低频超声治疗组和非低频超声治疗组，脑出血发生率分别为12.5％、11.25％（χ2=0.06，P＝0.99）。大鼠皮质区MMP-9及TIMP-1在尿激酶治疗组（50.05±6.19，48.24±7.06）、低频超声治疗组（37.45±7.21，43.67±8.12）、低频超声联合尿激酶治疗组（56.77±7.83，55.53±8.86）和对照组（29.23±5.61，33.33±5.79）表达差异有显著性（F=33.44，15.17，P均<0.01），三个治疗组MMP-9及TIMP-1表达均高于对照组（q=9.73，3.84，12.87；q=6.25，4.33，9.30；P均<0.01）。低频超声联合尿激酶治疗组与尿激酶治疗组MMP-9、TIMP-1表达差异有显著性（q=3.14；3.06；P均<0.01）。 　　结论低频超声可能具有增强尿激酶溶栓治疗脑梗死的作用，且不增加脑出血的发生。MMP-9及其抑制物TIMP-1在脑梗死尿激酶溶栓和低频超声治疗后的表达均增强。目的觀察低頻超聲聯閤尿激酶靜脈溶栓治療大鼠腦梗死的療效和基質金屬蛋白酶9（matrix metal oproteinase-9，MMP-9）及其抑製物1（tissue inhibitor of metal oproteinase-1，TIMP-1）在腦梗死溶栓治療後的錶達。 　　方法應用血栓栓塞法製備Wistar大鼠腦梗死模型160隻，隨機分為尿激酶治療組、低頻超聲治療組、低頻超聲聯閤尿激酶治療組和對照組。進行神經功能缺損評分（Neurological Severity Score，NSS）併測定腦梗死體積，免疫組化觀測MMP-9和TIMP-1的錶達。 　　結果治療前NSS評分尿激酶治療組（9.09±1.33）、低頻超聲治療組（9.16±1.23）、低頻超聲聯閤尿激酶治療組（9.11±1.45）和對照組（9.28±1.14）比較差異無顯著性（F=0.04，P＝0.99），治療後NSS評分尿激酶治療組（6.38±1.11）、低頻超聲治療組（7.37±1.35）和低頻超聲聯閤尿激酶治療組（5.08±1.31）均低于治療前（t分彆為4.95、3.10和6.52，P均＜0.01）。治療後梗死竈體積尿激酶治療組[（59.24±8.25）mm3]、低頻超聲治療組[（76.36±9.48）mm3]、低頻超聲聯閤尿激酶治療組[（56.01±9.77）mm3]均低于對照組[（94.90±11.09）mm3]（F=34.06，q=11.63、6.04、12.68；P均＜0.01）。根據治療方法不同分為尿激酶治療組和非尿激酶治療組，兩組大鼠腦齣血髮生率分彆為20％、3.75％（校正χ2=8.60，P＜0.01）；低頻超聲治療組和非低頻超聲治療組，腦齣血髮生率分彆為12.5％、11.25％（χ2=0.06，P＝0.99）。大鼠皮質區MMP-9及TIMP-1在尿激酶治療組（50.05±6.19，48.24±7.06）、低頻超聲治療組（37.45±7.21，43.67±8.12）、低頻超聲聯閤尿激酶治療組（56.77±7.83，55.53±8.86）和對照組（29.23±5.61，33.33±5.79）錶達差異有顯著性（F=33.44，15.17，P均<0.01），三箇治療組MMP-9及TIMP-1錶達均高于對照組（q=9.73，3.84，12.87；q=6.25，4.33，9.30；P均<0.01）。低頻超聲聯閤尿激酶治療組與尿激酶治療組MMP-9、TIMP-1錶達差異有顯著性（q=3.14；3.06；P均<0.01）。 　　結論低頻超聲可能具有增彊尿激酶溶栓治療腦梗死的作用，且不增加腦齣血的髮生。MMP-9及其抑製物TIMP-1在腦梗死尿激酶溶栓和低頻超聲治療後的錶達均增彊。
목적관찰저빈초성연합뇨격매정맥용전치료대서뇌경사적료효화기질금속단백매9（matrix metal oproteinase-9，MMP-9）급기억제물1（tissue inhibitor of metal oproteinase-1，TIMP-1）재뇌경사용전치료후적표체。 　　방법응용혈전전새법제비Wistar대서뇌경사모형160지，수궤분위뇨격매치료조、저빈초성치료조、저빈초성연합뇨격매치료조화대조조。진행신경공능결손평분（Neurological Severity Score，NSS）병측정뇌경사체적，면역조화관측MMP-9화TIMP-1적표체。 　　결과치료전NSS평분뇨격매치료조（9.09±1.33）、저빈초성치료조（9.16±1.23）、저빈초성연합뇨격매치료조（9.11±1.45）화대조조（9.28±1.14）비교차이무현저성（F=0.04，P＝0.99），치료후NSS평분뇨격매치료조（6.38±1.11）、저빈초성치료조（7.37±1.35）화저빈초성연합뇨격매치료조（5.08±1.31）균저우치료전（t분별위4.95、3.10화6.52，P균＜0.01）。치료후경사조체적뇨격매치료조[（59.24±8.25）mm3]、저빈초성치료조[（76.36±9.48）mm3]、저빈초성연합뇨격매치료조[（56.01±9.77）mm3]균저우대조조[（94.90±11.09）mm3]（F=34.06，q=11.63、6.04、12.68；P균＜0.01）。근거치료방법불동분위뇨격매치료조화비뇨격매치료조，량조대서뇌출혈발생솔분별위20％、3.75％（교정χ2=8.60，P＜0.01）；저빈초성치료조화비저빈초성치료조，뇌출혈발생솔분별위12.5％、11.25％（χ2=0.06，P＝0.99）。대서피질구MMP-9급TIMP-1재뇨격매치료조（50.05±6.19，48.24±7.06）、저빈초성치료조（37.45±7.21，43.67±8.12）、저빈초성연합뇨격매치료조（56.77±7.83，55.53±8.86）화대조조（29.23±5.61，33.33±5.79）표체차이유현저성（F=33.44，15.17，P균<0.01），삼개치료조MMP-9급TIMP-1표체균고우대조조（q=9.73，3.84，12.87；q=6.25，4.33，9.30；P균<0.01）。저빈초성연합뇨격매치료조여뇨격매치료조MMP-9、TIMP-1표체차이유현저성（q=3.14；3.06；P균<0.01）。 　　결론저빈초성가능구유증강뇨격매용전치료뇌경사적작용，차불증가뇌출혈적발생。MMP-9급기억제물TIMP-1재뇌경사뇨격매용전화저빈초성치료후적표체균증강。
Objective To observe the effect of low-frequency ultrasound combined with urokinase thrombolytic therapy for cerebral infarction in rats and the expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1). Methods One hundred and sixty cerebral infarction models were divided into 4 groups, including urokinase treatment group, low-frequency ultrasound treatment group, urokinase plus low-frequency ultrasound treatment group and control group. Neurological Severity Score (NSS), cerebral infarction volume and the expressions of MMP-9 and TIMP-1 were measured. Results The NSS of each group before the treatment (urokinase treatment group 9.09±1.33, low-frequency ultrasound treatment group 9.16±1.23, urokinase plus low-frequency ultrasound treatment group 9.11±1.45 and control group 9.28±1.14) had no signiifcant difference (F=0.04, P=0.99), but the NSS of three treatment groups after treatment (urokinase treatment group 6.38±1.11, low-frequency ultrasound treatment group 7.37±1.35, urokinase plus low-frequency ultrasound treatment group 5.08±1.31) after treatment were signiifcantly lower than that of before (t=4.95, 3.10, 6.52, P<0.01). The infarct volume in each treatment group [urokinase treatment group (59.24±8.25)mm3, low-frequency ultrasound treatment group (76.36±9.48)mm3, urokinase plus low-frequency ultrasound treatment group (56.01±9.77)mm3] was significantly lower than that of control group [(94.90±11.09)mm3] (F=34.06, q=11.63, 6.04, 12.68;P<0.01). The hemorrhagic rate in group with urokinase (20%) was higher than that of group without urokinase (3.75%) (χ2=8.60, P<0.01). There were no significant differences between the group with low-frequency ultrasound and the group without low-frequency ultrasound in hemorrhagic rates (12.5%vs 11.25%,χ2=0.06, P=0.99). The expressions of MMP-9/TIMP-1 in three treatment groups were signiifcantly higher than that of control group (F=33.44, 15.17, P<0.01;q=9.73, 3.84, 12.87;q=6.25, 4.33, 9.30;P<0.01). The expressions of MMP-9/TIMP-1 in urokinase plus low-frequency ultrasound treatment group were signiifcantly higher than that of urokinase treatment group (q=3.14;3.06;P<0.01). Conclusion Low-frequency ultrasound maybe enhance the effect of urokinase thrombolytic therapy for cerebral infarction in rats and have no increased hemorrhagic rate. The expressions of MMP-9 and TIMP-1 increasing after urokinase thrombolytic therapy or low-frequency ultrasound were found.