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目的观察低频超声辅助尿激酶静脉溶栓治疗大鼠急性脑梗塞后基质金属蛋白酶-9(MMP-9)的变化,探讨其在低频超声助溶脑缺血再灌注损伤及出血性转化中的作用。方法应用血栓栓塞法制备Wistar大鼠脑梗塞模型,分别给予尿激酶、低频超声照射,采用NSS评价治疗前后神经功能,采用红四氮唑染色法测定脑梗塞体积,采用免疫组化法监测MMP-9的表达。结果梗塞组用药前后NSS评分差异不明显(t=0.85,P>0.05);尿激酶组、低频超声加尿激酶组给药后24hNSS评分明显低于溶栓前(t=12.59,t=15.31,P均<0.01)。3组梗塞灶体积有显著性差异(F=125.99,P<0.01),尿激酶组、低频超声加尿激酶组梗塞灶体积显著小于梗塞组(q=18.02,P<0.01;q=20.62,P<0.01),两组之间差异不显著(q=2.59,P>0.05)。尿激酶组和低频超声加尿激酶组MMP-9表达阳性率及光密度值均显著高于梗塞组(F=78.92,F=209.14,P<0.01),两组之间差异不明显(q=2.86,2.47,P>0.05)。结论尿激酶在脑梗死超早期有显著溶栓作用,低频超声波具有显著的协助尿激酶溶栓作用,可以减少尿激酶用量,MMP-9可能在脑梗塞后溶栓的出血转化中起着重要作用。
Objective To observe the changes of matrix metalloproteinase-9 (MMP-9) after low-frequency ultrasound-assisted urokinase intravenous thrombolysis in acute cerebral infarction in rats and its role in ischemia-reperfusion injury and hemorrhagic transformation in low-frequency ultrasound . Methods Wistar rat models of cerebral infarction were established by thromboembolism. Urokinase and low-frequency ultrasound were respectively used to evaluate the neurological function of the infarcted rats. NSF was used to evaluate the neurological function. The infarct volume was measured by red tetrazolium staining. The expression of MMP- 9 expression. Results The NSS score of infarction group was not significantly different before and after treatment (t = 0.85, P> 0.05) .NSS score of urokinase group and low-frequency ultrasound plus urokinase group was significantly lower than that before thrombolysis (t = 12.59, t = 15.31, P <0.01). The volume of infarction in 3 groups was significantly different (F = 125.99, P <0.01). The volume of infarction in urokinase group and low-frequency ultrasound plus urokinase group was significantly smaller than that of infarction group (q = 18.02, P <0.01; <0.01). There was no significant difference between the two groups (q = 2.59, P> 0.05). The positive rate and optical density of MMP-9 in urokinase group and low-frequency ultrasound plus urokinase group were significantly higher than those in infarction group (F = 78.92, F = 209.14, P <0.01) 2.86, 2.47, P> 0.05). Conclusion Urokinase has significant thrombolysis in the early stage of cerebral infarction. Low-frequency ultrasound can significantly reduce the amount of urokinase, which may assist in the thrombolysis of urokinase. MMP-9 may play an important role in the hemorrhage and conversion of thrombolysis after cerebral infarction .