阿托伐他汀联合尿激酶溶栓治疗对大脑中动脉梗死大鼠caspase-3表达的影响

Effects of Atorvastatin joint urokinase thrombolysis treatment on the expression of caspase-3 in rats with middle cerebral artery occlusion

目的观察阿托伐他汀联合尿激酶溶栓治疗对大脑中动脉梗死(MCAO)大鼠脑组织caspase-3表达的影响。方法采用血栓栓塞法制备SD大鼠大脑中动脉急性脑梗死模型,随机分为阿托伐他汀组、尿激酶组、联合治疗组和对照组。缺血3 h给予阿托伐他汀或相同体积生理盐水,缺血4 h给予尿激酶或相同体积生理盐水治疗。治疗前3h和缺血24h行神经功能缺损评分,缺血24h取脑,采用氯化三苯四唑(TTC)染色法观察脑梗死体积,免疫组织化学法检测大鼠脑组织caspase-3的表达。结果与对照组比较,阿托伐他汀组、尿激酶组和联合治疗组大鼠缺血24 h神经功能缺损评分明显降低(P<0.05),梗死体积明显缩小(P<0.05)。与阿托伐他汀组比较,尿激酶组和联合治疗组神经功能改善程度及梗死体积减小程度更显著(P<0.05)。各组大鼠均未发现脑出血。与对照组相比,阿托伐他汀组和联合治疗组caspase-3表达显著减少(P<0.05)。与阿托伐他汀组比较,联合治疗组caspase-3减少更为明显(P<0.05)。与对照组相比,尿激酶组caspase-3表达无统计学差异(P>0.05)。结论阿托伐他汀联合尿激酶溶栓治疗脑梗死能更大程度降低caspase-3的表达,有提高疗效的趋势。

Objective To study the effects of atorvastatin joint urokinase thrombolysis treatment on the expression of caspase-3 in rats with middle cerebral artery occlusion. Methods TThe embolic middle cerebral artery occlusion model was induced in forty-eight male Sprague-Dawley rats. The rats were randomly divided into atorvastatin group, urokinase group, combination treatment group and blank control group. 3 hours after the occlusion, rats were treated with atorvastatin or saline. 4 hours after the occlusion, they were treated with urokinase or saline. The modified neurological severity score at 3h and 24h and infarction volume at 24h after middle cerebral artery occlusion were measured. Immunohistochemical meth- od was used to detect the caspase-3 expression in brain tissue. Results Compared with the control group,the mNSS scores and infarction volume in atorvastatin group, urokinase group, combination treatment group are significantly lower 24h after middle cerebral artery occlusion（P 〈 0.05）. Compared with the atorvastatin group,the NIHSS score and infarction volume of the urokinase group and combination treatment group bad significant better improvement（ P 〈 0.05 ）. There were no cere- bral hemorrhage in any groups. Compared with the control group, the expression of caspase-3 in atorvastatin group and com- bination treatment group were significantly lower （ P 〈 0.05 ）, Compared with the atorvastatin group, the expression of caspase-3 in combination treatment group were lower（ P 〈 0.05 ） ,There were no statistical differences in control group and urokinase group of caspase-3 expression（ P 〉 0.05 ）. Conclusion Atorvastatin joint urokinase thrombolysis treatment can reduce the expression of caspase-3 more in rats with brain ischemia, Combined with urokinase, atorvastatin can improve the effect of thrombolytic therapy.