瑞舒伐他汀介入治疗对脑出血急性期大鼠血肿周围脑组织的影响

Effect of rosuvastatin interventional therapy in brain tissue around hematoma of cerebral hemorrhage rats at acute phase

目的观察瑞舒伐他汀介入治疗对脑出血急性期大鼠血肿周围脑组织核转录因子-κB(NF-κB)及Notch1表达的影响。方法选取64只SD大鼠以立体定向仪脑内注射自体血构建脑出血大鼠模型,建模成功后将其随机分为模型组(n=32)及实验组(n=32),另选32只SD大鼠,脑内注射等量生理盐水作为假手术组(n=32)。实验组建模后2 h后以微创介入联合术后10 mg·kg^(-1)·d^(-1)瑞舒伐他汀灌胃治疗,假手术组及模型组则仅灌胃等量生理盐水,每天1次,灌胃5d。以Garcia评分法评估并比较各组大鼠术后12,24,72 h及5 d时的神经功能;另以免疫组化法检测术后各组血肿周围组织核转录因子κB亚基p65(NF-κB p65)及Notch1蛋白表达情况。结果术后6 h至术后5 d,模型组及实验组大鼠Garcia评分均呈先降低后升高趋势(P<0.05),且均以72 h最低;与假手术组比较,模型组及实验组大鼠Garcia评分均显著降低(P<0.05),与模型组比较,术后24,72 h和5 d实验组大鼠Garcia评分显著升高(P<0.05)。术后5 d,假手术组、模型组及实验组大鼠血肿周围组织Notch1蛋白阳性细胞比例分别为(4.68±1.27)%,(40.23±3.14)%,(22.35±3.93)%;NF-κB p56蛋白阳性细胞比例分别为(5.05±2.01)%,(50.63±1.80)%,(39.38±1.78)%。术后72h和5 d,模型组及实验组大鼠血肿周围组织Notch1、NF-κB p56蛋白阳性细胞比例均显著高于假手术组(P<0.05),且实验组均显著低于模型组(P<0.05)。结论瑞舒伐他汀介入治疗可显著改善脑出血急性期大鼠神经功能,其作用机制可能与显著下调血肿周围脑组织NF-κB p65及Notch1蛋白表达相关。

Objective To explore the effect of rosuvastatin interventional therapy on the expression of nuclear transcription factor-κB（ NF-κB） and Notch1 in brain tissue around hematoma of cerebral hemorrhage rats at acute phase. Methods Sixty-four SD rats were bulit cerebral hemorrhage rats model by intracerebral injection autoblood using stereotaxic apparatus and were randomly divided into model group（ n = 32） and test group（ n = 32） after built successfully,another 32 rats were selected and intracerebral injected with equivalent normal saline,as sham-operation group（ n = 32）,test group were treated with minimally invasive interventional and gavaged 10 mg·kg^-1·d^-1 rosuvastatin at 2 h after operation,sham-operation group and model group were gavaged with equivalent normal saline,1 time a day,gavaged for 5 d. The nervefunction at 12,24,72 h and 5 d after operation were evaluated and compared by Garcia scoring method; and the expression of nuclear transcription factor-κB subunit p65（ NF-κB p65） and Notch1 proteins in brain tissue around hematoma of cerebral hemorrhage rats were detected and compared by immunohistochemical method. Results From 12 h after operation to 5 d after operation,the rat Garcia scores in model group and test group showed a trend of first decreased and then increased（ P〈0. 05）,and which was lowest at 72 h after operation. Compared with sham-operation group,the Garcia scores in model group and test group decreased（ P〈0. 05）. The Notch1 protein positive cells proportion in rat brain tissue around hematoma of sham-operation group,model group and test group on 5 d after operation were（ 4. 68 ± 1. 27） %,（ 40. 23 ± 3. 14） %,（ 22. 35 ± 3. 93） %; the NF-κB p65 protein positive cells proportion were（ 5. 05 ± 2. 01） %,（ 50. 63 ± 1. 80） %,（ 39. 38 ± 1. 78） %. The Notch1 and NF-κB p65 protein positive cells proportions in rat brain tissue around hematoma of model group and test group at 72 h and 5 d after operation were higher than that in sham-operation group（ P〈0. 05）,and test group was lower than model group（ P〈0. 05）.Conclusion Rosuvastatin interventional therapy can improve the nerve function of cerebral hemorrhage rats at acute phase effectively,and the mechanism maybe related to the down-regulation of brain tissue around hematoma NF-κB p65 and Notch1 protein expression.