通心络对大脑中动脉栓塞模型大鼠脑缺血后脑组织caspase-3、P53和HSP70的影响  

Experimental Study on Tongxinluo Affecting the Expression of Caspase-3,P53 and HSP70 in Brain Tissue after Cerebral Ischemia of MCAO Model Rats

作　　者：吴以岭 袁国强 贾振华 吴正国 高怀林 吴相春 魏聪 

机构地区：[1]河北以岭医药研究院络病研究室,河北石家庄050035

出　　处：《中国神经免疫学和神经病学杂志》2007年第5期284-288,共5页Chinese Journal of Neuroimmunology and Neurology

基　　金：国家重点基础研究发展"973"计划基金资助项目(2005CB523301)

摘　　要：目的探讨通心络胶囊在缺血脑保护方面的作用机制。方法采用线栓法制备大鼠大脑中动脉闭塞(MCAO)模型。将SD大鼠随机分为假手术组、MCAO模型组、MK-801组及通心络大、小剂量治疗组。MK-801组按体重0.5 mg/(kg.d)经腹腔注射MK-801,1次/d;通心络大、小剂量治疗组分别按体重1.0、0.5 g/(kg.d)给予通心络原粉灌胃,2次/d。采用流式细胞、Western blot及RT-PCR技术观察通心络对大鼠脑缺血后神经细胞凋亡率和caspase-3、P53、HSP70蛋白及其mRNA表达的影响。结果通心络和MK-801均可明显降低MCAO模型大鼠缺血后各时间点脑部神经细胞凋亡百分率(P<0.05,P<0.01),以通心络大剂量治疗组效果最显著;模型组caspase-3、P53蛋白及其mRNA表达较假手术组4明显增高,通心络和MK-801均可使其表达降低,其中通心络大剂量治疗组最显著(P<0.01);与模型组比较,各治疗组HSP70蛋白及其mRNA表达明显增高(P<0.05,P<0.01)。结论通心络可降低MCAO模型大鼠神经细胞凋亡百分率而发挥脑保护作用,其机制可能与抑制细胞凋亡相关因子caspase-3、P53表达及促进应激保护性HSP70表达有关。Objective To approach the therapeutic mechanism of Tongxinluo （TXL） capsule in the conservative aspect of the cerebral ischemia. Methods SD rats were divided into five groups in random： sham operation group, MCAO （middle cerebral artery occlution） group, MK-801 group, TXL large dose group, TXL small dose group. After the preparation of MCAO, peritoneal injection of MK-801 0.5 mg/（kg·d） in MK-801 group, twice every day. TXL large dose group and TXL small dose group 1.0 g/（kg·d） and 0.5 g/（kg·d） respectively, original TXL powder was administered intragastrically, twice every day. To observe the effect on the rate of nerve cell apoptosis, caspase-3, P53 and HSP70 protein and mRNA expression using flow cytometry, Western blot and RT-PCR technique. Results TXL and MK-801 all obviously cut down the rate of model rat IDEM effect apoptosis （P〈0.05 ,P〈0.01）, the TXL large dose group got the most significant effect; caspase-3, P53 protein and mRNA expression in the MCAO group were higher than those in the sham operated group, TXL and MK-801 reduced the expressions; the TXL large dose group got the most significantly change（P〈0.01）. Compared to the MCAO model group, HSP70 protein and mRNA expression obviously increase in all treated groups （P〈0. 05,P〈0.01）. Conclusions TXL has got neuroprotection effect according to reduce the rate of MCAO model rat nerve cell apoptosis, the mechanism maybe related to inhibit apoptosis correlation factors caspase-3, P53 expression, and to promote stress protection nature of HSP70 expression.

关 键 词：通心络胶囊 大脑中动脉闭塞 MK-801 CASPASE-3 P53 HSP70 

分 类 号：R743.3[医药卫生—神经病学与精神病学]