川芎嗪对小鼠颅脑损伤后大脑组织细胞凋亡相关因子的影响

Effects of Ligustrazine on apoptosis related factors in brain tissues of mice after craniocerebral injury

目的:研究川芎嗪对小鼠颅脑损伤(CI)后的细胞凋亡通路中相关蛋白及其mRNA的影响,揭示川芎嗪治疗颅脑损伤的可能作用机制。方法:将50只昆明种小鼠,随机分成假手术组、模型组、川芎嗪治疗组(40,80,160 mg·kg^(-1))五组,采用改良的Feeney自由落体损伤装置建立小鼠CI模型。造模3 d后开始灌胃治疗,每日1次,其他各组给予等量生理盐水,连续用药20 d;蛋白免疫印迹和RT-PCR技术分别检测小鼠大脑组织中凋亡相关蛋白及其mRNA(Bax、Bcl-2、Caspase-9和Caspase-3)的表达量。结果:与假手术组相比,模型组小鼠大脑的凋亡蛋白Bax、Caspase-3和Caspase-9及其mRNA表达增加,差异极显著(P<0.01,P<0.01,P<0.01),抗凋亡蛋白Bcl-2及其mRNA表达差异无统计学意义(P>0.05);与模型组相比,治疗组大脑凋亡蛋白Bax、Caspase-3和Caspase-9及其mRNA表达降低,差异极显著(P<0.01,P<0.01,P<0.01),抗凋亡蛋白Bcl-2及其mRNA表达增加,差异极显著(P<0.01)。结论:川芎嗪可能通过上调Bcl-2蛋白及其mRNA的表达,抑制Bax、Caspase-3和Caspase-9蛋白及其mRNA的表达,减少大脑组织细胞凋亡,保护大脑组织。

OBJECTIVE To investigate the effects of ligustrazine on the expression of related proteins and mRNA in the apoptosis pathway,to explore the possible mechanism of ligustrazine in the treatment of brain neuron apoptosis after craniocerebral injury in mice.METHODS Fifty Kunming mice were randomly divided into five groups：sham operation group,model group and ligustrazine treatment groups（40,80,160 mg·kg^（-1））.The brain injury was induced by modified Feeney free falling injury device.After 3 days of injury,the mice were given intragastric administration once a day.Mice in other groups were given the same volume of stroke physiological saline solution.All treatments were continued for 20 days consecutively.Bax,Bcl-2,Caspase-9 and Caspase-3 in the brain tissues of the mice were detected by immunoblotting and RT-PCR.RESULTS Compared with the sham operation group,the expressions of Bax,Caspase-3 and Caspase-9 in the model group increased significantly（P0.01,P0.01 and P0.01,respectively）,whereas the expression of Bcl-2 was not significantly different（P0.05）.Compared with the model group,the expressions of Bax,Caspase-3 and Caspase-9 in the treatment group decreased significantly（P0.01,P0.01 and P0.01,respectively）,and the expression of Bcl-2 increased significantly（P0.01）.CONCLUSION Ligustrazine may protect the brain by upregulating Bcl-2,inhibiting Bax,Caspase-3 and Caspase-9,thereby reducing the apoptosis of brain tissue cells.