川芎嗪对大鼠急性胸部撞击伤所致肺组织细胞异常凋亡抑制作用的机制研究

Ligustrazine Attenuates the Apoptosis in Acute Lung Injury Induced by Blunt Chest Trauma

目的:探讨川芎嗪对大鼠急性肺部撞击伤所致异常凋亡抑制作用及其机制。方法:健康雄性SD大鼠72只,随机分为正常对照组(C组,n=24)、肺部撞击伤模型组(T组,n=24)、川芎嗪治疗组(L组,n=24)。C组无特殊处理,L组在撞击后立即腹腔注射川芎嗪80mg/kg 1次。细胞凋亡原位检测(TUNEL)法测定肺组织内细胞凋亡;检测肺水肿程度和肺血管通透性以检测肺功能改变,免疫组织化学检测肺组织Bcl-2、Bax和Caspase-3的表达;光镜和电镜下观察肺组织病理改变。结果:T组肺组织内细胞凋亡指数及肺组织损伤程度明显增高(均P<0.05);肺血管通透性增强(P<0.05),肺水肿程度增加(P<0.05);Caspase-3、Bax、Bcl-2表达较C组升高(P<0.05),Bcl-2/Bax比值降低。L组相对于T组肺组织内细胞凋亡指数及肺组织损伤程度降低(P<0.05),肺血管通透性破坏降低(P<0.05),肺水肿程度减轻(P<0.05);Caspase-3、Bax表达下降(P<0.05),而Bcl-2表达增强,Bcl-2/Bax比值增加(P<0.01)。结论:川芎嗪可通过抑制肺组织细胞凋亡减轻肺损伤,其机制可能是提高Bcl-2/Bax的比值,降低Caspase-3的表达水平来实现的。

Objective： To investigate the protective effect of ligustrazine on apoptosis of lung tissue cells and its mechanism in acute lung injury following blunt chest trauma in rats.Methods： A total of 72 SD rats weighing（250±25） g were divided equally and randomly into three groups： the normal control group（C group,n=24）,trauma model group（T group,n=24）,and ligustrazine treatment group（L group,n=24）.Rats in L group were intraperitoneal injected with 80 mg/kg ligustrazine immediately after blunt chest trauma,cell apoptosis in lung tissue were measured by TUNEL method,and the apoptotic index was calculated.Pulmonary microvascular permeability and assessment of pulmonary edema was detected to assess the lung function.Expressions of Caspase-3,Bax,and Bcl-2 were detected by immunohisto-chemical staining of SABC.Lung tissue sections were made for light and electron microscopic observation.Results： The mean Evans blue dye concentration and the mean wet/dry weight ratio of lung in T group were significantly higher than those in group control（P0.05）,while both were significantly decreased in L group than in T group control（P0.05）.In the T group,apoptotic index and expressions of Caspase-3,Bax,and Bcl-2 were higher than those in C group（P0.05）,the ratio of Bcl-2/Bax markedly decreased（P0.01）,lung tissue injuries were significant under light microscope,and apoptotic cells increased obviously under transmission electron microscope.As compared with T group,apoptotic index and expressions of Caspase-3 and Bax decreased in L group（P0.05）,the expression of Bcl-2 increased（P0.01）,the ratio of Bcl-2/Bax increased（P0.01）,the injury of lung tissue was relieved,and apoptotic cells decreased obviously in transmission electron microscopic observation.Conclusion： Ligustrazine could alleviate apoptosis induced by blunt chest trauma through the procedure of enhancing the ratio of Bcl-2/Bax and decreasing the expression of Caspase-3.