阿魏酸对蛛网膜下腔出血模型大鼠脑干组织和基底动脉细胞凋亡的影响

Effects of ferulic acid on apoptosis of cells in brainstem tissue and basilar artery in subarachnoid hemorrhage(SAH)model rat

目的:探讨阿魏酸对蛛网膜下腔出血(SAH)大鼠脑干组织神经细胞和基底动脉细胞凋亡的影响。方法:将50只雄性SD大鼠随机分为假手术组、SAH模型组,阿魏酸低(20 mg·kg-1)、中(40 mg·kg-1)和高(80 mg·kg-1)剂量组,采用枕大池内新鲜自体动脉血二次注入法建立大鼠蛛网膜下腔出血模型,术后各治疗组灌胃给药7 d,假手术组和模型组均给予等体积生理盐水。分别采用TUNEL技术和免疫组化法观察脑干组织神经细胞凋亡和基底动脉细胞中caspase-3的表达。结果:与假手术对照组比较,SAH大鼠脑干组织中神经细胞凋亡阳性率明显升高(P<0.01),基底动脉血管内皮细胞和平滑肌细胞中caspase-3表达显著增加(P<0.01),而SAH大鼠灌胃服用阿魏酸7 d后,阿魏酸低、中和高剂量组(20,40,80 mg·kg-1)大鼠脑干组织中神经细胞凋亡率均显著降低(P<0.05,P<0.01,P<0.01),动脉基底血管内皮细胞和平滑肌细胞中caspase-3阳性表达率明显降低。结论:阿魏酸通过抑制脑干组织和基底动脉细胞中凋亡相关基因的表达,从而达到对SAH大鼠脑功能的保护作用。

OBJECTIVE To investigate the effects of ferulic acid（FA）on apoptosis of cells in brainstem tissue and basilar artery in rats with subarachnoid hemorrhage（SAH）.METHODS A total of 50 male Sprage-Dawley（SD）rats were randomly divided into five groups：sham operation group,SAH model group,experimental groups treated with FA at low-dose（20 mg·kg^-1）,middle-dose（40 mg·kg^-1）and high-dose（80 mg·kg^-1）.The model of SAH rats were built by twice injection of fresh autohemic arterial blood into the cisterna magna.After operation,experimental groups of rats were intragastrically administered FA for 7 days,and rats in sham operation group and model group were intragastrically administered the same volume of 0.9%normal saline.TUNEL technique and immunohistochemistry were used to observe apoptosis of brainstem neural cells and expression of casp ase-3 in basilar artery cells.RESULTS Compared with sham operation group,apoptosis of brainstem neural cells in SAH rats significantly increased,positive percentages of caspase-3 expression in basilar artery endothelia and smooth muscle cells in SAH rats also increased significantly（P〈0.01）.After continuous administration of FA for 7 days,the apoptosis rate of brainstem neural cells significantly decreased in rats administered FA at all doses（20,40,80 mg·kg^-1）（P〈0.05,P〈0.01,P〈0.01）,while positive percentages of caspase-3 expression significantly decreased in basilar artery endothelia and smooth muscle cells.CONCLUSION By inhibiting apoptosis of brainstem neural cells and expression of caspase-3 gene in basilar artery,FA can provide protective effects on brain in SAH rats.