甘草甜素对大鼠蛛网膜下腔出血后脑损伤的治疗作用及对SIRT1通路的影响

Glycyrrhizin on the treatment of early brain injury after subarachnoid hemorrhage in rats and its influence on SIRT1 pathway

目的探讨甘草甜素对大鼠蛛网膜下腔出血(SAH)后脑损伤的治疗作用及对SIRT1通路的影响。方法血管内穿孔制备蛛网膜下腔出血大鼠模型,随机分为模型组、尼莫地平组、甘草甜素低剂量组、甘草甜素高剂量组,另设正常组。治疗8周后,测定各组神经功能缺损评分、伊文思蓝渗出量、TUNEL阳性细胞、蛛网膜下腔出血组织SIRT1 mRNA、HMGB1 mRNA及蛋白水平。结果与正常组比较,模型组、尼莫地平组和甘草甜素低、高剂量组大鼠神经功能缺损评分、伊文思蓝渗出量、TUNEL阳性细胞比例升高(P<0.01);尼莫地平、甘草甜素治疗干预后,与模型组相比,大鼠神经功能缺损评分、伊文思蓝渗出量、TUNEL阳性细胞比例降低,且甘草甜素低、高剂量组呈剂量依赖性(P<0.01);甘草甜素高剂量组与尼莫地平组疗效相似(P>0.05)。与正常组比较,模型组、尼莫地平组和甘草甜素低、高剂量组大鼠脑组织SIRT1mRNA及蛋白水平降低,HMGB1 mRNA及蛋白水平升高,差异有统计学意义(P<0.01);在使用尼莫地平和甘草甜素治疗后,与模型组相比,大鼠脑组织SIRT1 m RNA及蛋白水平升高,HMGB1 mRNA及蛋白水平降低,且甘草甜素低、高剂量组呈剂量依赖性,差异有统计学意义(P<0.01);尼莫地平组和甘草甜素高剂量组作用相似(P>0.05)。结论甘草甜素对SAH后神经功能损伤具有改善作用,能明显抑制脑部水肿,神经细胞凋亡。其机制可能与甘草甜素激活SIRT1通路进而抑制HMGB1的表达有关。

Objective To investigate the treatment of glycyrrhizin on early brain injury after subarachnoid hemorrhage(SAH)in rats and its effect on SIRT1 pathway. Methods A subarachnoid hemorrhage rat model was prepared by intravascular perforation,which was randomly divided into model group,nimodipine group,glycyrrhizin low-dose group,glycyrrhizin highdose group,and normal group. After 8 weeks of treatment,the nerves functional impairment score,Evans blue exudation,TUNEL positive cells,SIRT1 m RNA and HMGB1 m RNA and protein levels in subarachnoid hemorrhage tissue were measured. Results Compared with normal group,the rats in model group,nimodipine group and each glycyrrhizin group increased in neurological deficit scores,the amount of Evans blue exudation,and the proportion of TUNEL positive cells(P<0.01);after nimodipine and glycyrrhizin treatment intervention,compared with model group,the rat neurological deficit score,the amount of Evans blue exudation,and the proportion of TUNEL positive cells decreased,and the glycyrrhizin low-and high-dose group was dosedependent(P<0.01);high-dose glycyrrhizin group had similar efficacy as nimodipine group(P>0.05). Compared with normal group,the brain SIRT1 m RNA and protein level of model group,nimodipine group and glycyrrhizin group decreased,and the HMGB1 m RNA protein level increased,the difference was statistically significant(P<0.01);after treatment with nimodipine and glycyrrhizin,compared with model group,rat brain tissue SIRT1 m RNA protein level increased,HMGB1 m RNA protein level decreased,and glycyrrhizin low-and high-dose groups were dose-dependent,the difference was statistically significant(P<0.01);the effects of nimodipine group and high-dose glycyrrhizin group were similar(P>0.05). Conclusion Glycyrrhizin can improve neurological damage after SAH,and can significantly inhibit brain edema and neuronal apoptosis. Its mechanism may be related to the activation of SIRT1 pathway by glycyrrhizin,which inhibits the expression of HMGB1.