【摘要】 目的探讨阿托伐他汀对局灶缺血性大鼠脑水肿的影响及对水通道蛋白(aquaporin,AQP)的调节作用。方法选择健康清洁级成年雄性SD大鼠60只,采用随机数表法随机分为假手术组,模型组,阿托伐他汀组,每组20只。模型组和阿托伐他汀组采用大脑中动脉栓塞再灌注法造模。阿托伐他汀组术前连续7 d给予阿托伐他汀5 mg/(kg·d)灌胃,模型组及假手术组连续7 d接受等剂量生理盐水。大鼠脑缺血再灌注24 h后解剖取材,测定脑组织含水量,RT-PCR和蛋白免疫印迹法分别检测AQP-1、AQP-4、AQP-9 mRNA和蛋白表达。结果假手术组、模型组和阿托伐他汀组脑组织含水率比较,差异有统计学意义(F=21.767,P=0.000)。模型组脑组织含水率明显高于假手术组[(63±9)%vs(42±4)%,P<0.01];阿托伐他汀组脑组织含水率明显低于模型组,差异有统计学意义[(49±2)%vs(63%±9)%,P<0.01]。3组AQP4 mRNA和蛋白表达比较,差异有统计学意义(P=0.000)。模型组AQP4 mRNA和蛋白表达明显高于假手术组(1.27±0.17 vs 0.43±0.06,0.25±0.03 vs 0.10±0.01,P<0.01);阿托伐他汀组AQP4 mRNA和蛋白表达明显低于模型组(0.61±0.07 vs 1.27±0.17,0.16±0.04 vs 0.25±0.03,P<0.01)。结论阿托伐他汀能减轻脑缺血再灌注大鼠的脑水肿,其作用机制可能是通过抑制AQP4的表达。更多还原

【Abstract】 Objective To study the effect of atorvastatin on cerebral edema and aquaporin(AQP) in focal ischemic rats.Methods Sixty healthy adult male SD rats were randomly divided into sham operation group,model group and atorvastatin treatment group(20 in each group).A cerebral I/R model of rats was established by middle cerebral artery embolization and reperfusion for model group and atorvastatin treatment group.The rats in atorvastatin treatment group were given atorvastatin(5 mg/kg·d) and those in model group and sham operation were given an equivalent normal saline for 7 days before operation.Tissue samples were taken from the animals after 24 h of cerebral I/R.The water content in brain tissue was measured.The expressions of AQP-1,AQP-4 and AQP-9 mRNA and protein were detected by RT-PCR and Western blot respectively.Results The water content in brain tissue was significantly different in 3 groups(F=21.767,P=0.000) and was significantly higher in model group than in sham operation group and significantly lower in atorvastatin treatment group than in model group(63%±9% vs 42%±4%,P<0.01;49%±2% vs 63%±9%,P<0.01).The AQP4 mRNA and protein expression levels were significantly different in 3 groups(P=0.000) and were significantly higher in model group than in sham operation group and significantly lower in atorvastatin treatment group than in model group(1.27±0.17 vs 0.43±0.06,0.25±0.03 vs 0.10±0.01,P<0.01;0.61±0.07 vs 1.27±0.17,0.16±0.04 vs 0.25±0.03,P<0.01).Conclusion Atorvastatin reduces cerebral edema in cerebral I/R rats by inhibiting the expression of AQP-4.更多还原