摘要
目的:观察化痰通络方对急性脑梗死大鼠重组组织纤溶酶原激活剂(rt-PA)溶栓后内质网应激(endoplasmic reticulum stress,ERS)后期神经细胞凋亡途径中生长抑制DNA损伤基因153(C/EBP homologous protein,GADD153/CHOP)和c-Jun氨基末端激酶-1(c-Jun NH2-terminal kinases-1,JNK1)基因表达的影响。方法:将160只健康SD大鼠随机分为假手术组,模型组,rt-PA组,化痰通络方联合rt-PA组(简称中药组)。采用自身栓子法制备大鼠大脑中动脉栓塞模型(MCAO),rt-PA组与中药组分别给予尾静脉注入rt-PA(5.67 mg·kg-1)及联合化痰通络中药(7.2 g·kg-1)干预,2次/d。于6 h,1,3,7 d 4个时相分别采用RT-PCR检测各组大鼠大脑皮质梗死区组织中GADD153/CHOP与JNK1 mRNA的表达,采用TUNEL法检测各组大鼠大脑神经元细胞的凋亡。结果:与假手术组比较,模型组在4个时相中GADD153/CHOP与JNK1基因表达均明显增高(P<0.05),同一时相内与假手术组比较,模型组神经元凋亡显著升高(P<0.05);与模型组比较,rt-PA组和中药组在4个时相中均可降低JNK1 mRNA的表达量(P<0.05),同时rt-PA组在1 d时可降低GADD153/CHOP mRNA的表达,而中药组可在6 h和1 d时同时降低其表达,差异显著(P<0.05),rt-PA组在1 d和7 d时相神经元凋亡明显低于模型组(P<0.05),中药组各个时相神经元凋亡均显著降低(P<0.05),但rt-PA组与中药组之间无明显差异。结论:化痰通络方可通过降低内质网应激后期神经细胞凋亡途径中GADD153/CHOP与JNK1 mRNA的表达,部分抑制神经细胞的凋亡,从而防治急性脑梗死溶栓后缺血再灌注的发生与发展。
Objective： To observe the effect of Huatan Tongluo formulae on expression of C /EBP homologous protein（ GADD153 / CHOP） and C-Jun NH2-terminal Rinases（ JNK1） in apoptosis pathway of endoplasmic reticulum stress in rat reconstructive tissue plasminogen activator（ rt-PA） after the acute cerebral infarction. Method： The 160 healthy male SD rats were randomly divided into sham group,model group,rt-PA group,rt-PA-Huatan Tongluo group（ Chinese medicine group for short）. Own embolus method was used to establish rat models of middle cerebral artery embolism（ MCAO）. The rats in rt-PA group were injected with rt-PA（ concentration of 5. 67 mg·kg^- 1）,and those of Chinese medicine group were given with rt-PA and Chinese medicine Huatan Tongluo formulae（ 7. 2 g·kg^- 1）,2 times a day. RT-PCR was used in four time phases of 6hours,1 day,3,7 days to detect the expression of GADD153 / CHOP and JNK1 mRNA in cerebral cortex infarction tissues in rats. TUNEL method was used to detect brain neurons apoptosis in rats. Result： Compared with sham group,the gene expression of GADD153 / CHOP and JNK1 in 4 time phases was significantly higher in model group（ P 〈0. 05）. Compared with sham group within the same time phase,neurons apoptosis in model group was significantly increased（ P 〈0. 05）. Compared with the model group,the expression of JNK1 mRNA was decreased in 4 time phases in both rt-PA group and Chinese medicine group（ P 〈0. 05）,and rt-PA group could decrease GADD153 / CHOP mRNA expression on 1 d while Chinese medicine group could decrease the expression on 6 h and1 d,with significant difference（ P 〈0. 05）. Neurons apoptosis in rt-PA group on 1 and 7 d was significantly lower than that in the model group（ P 〈0. 05）,while Chinese medicine group decreased neurons apoptosis in various time phases（ P 〈0. 05）. However,there was no significant difference between rt-PA group and Chinese medicine group. Conclusion： Huatan Tongluo formulae can prevent and treat partially reperfusion injury after acute cerebra accepted thrombolysis by reducing GADD153 / CHOP and JNK1 mRNA expression in apoptosis pathway of endoplasmic reticulum stress,and partially inhibiting the apoptosis of nerve cells.
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2015年第23期117-121,共5页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金项目(81273942)
天津市应用基础及前沿技术研究计划项目(12JZDJC25300)
天津市教委"十二五"创新团队培养计划项目(TD12-5035)
