依达拉奉联合川陈皮素治疗脑梗死大鼠的效果及对microRNA-24、HMGB1水平的影响分析

Effect ofEdaravone Combined with Nobiletin on Rats with Cerebral Infarction and Its Effect on microRNA-24 and HMGB1 Levels

目的探讨依达拉奉联合川陈皮素治疗脑梗死大鼠的效果及对微小RNA-24(microRNA-24,miRNA-24)和高迁移率族蛋白1(high mobility group box 1,HMGB1)水平的影响。方法选择180只SD雄性小鼠,按照随机数字表法分为5组,对照组、模型组、依达拉奉组、川陈皮素组以及联合给药组,每组36只。除对照组外,其余4组均构建中动脉闭塞(middle cerebral artery occlusion,MCAO)模型,并按照不同时间点(1、3、5、7 d)分为4个亚组,各给药组术后腹腔注射相应药物,各亚组分别给药相应时间,1次/d,对照组和模型组分别注射等体积0.9%NaCl溶液。比较各组大鼠神经功能缺损评分、脑组织梗死体积和含水量,同时对各组microRNA-24和HMGB1水平进行比较。结果模型组和各给药组神经功能缺损评分、脑组织梗死体积和含水量均显著高于对照组(P<0.05);各给药组神经功能缺损评分、脑组织梗死体积和含水量显著低于模型组(P<0.05);相同时间点联合给药组神经功能缺损评分、脑组织梗死体积和含水量显著低于依达拉奉组和川陈皮素组;与对照组相比,其余各组microRNA-24表达显著降低,血清HMGB1水平显著增高(P<0.05),与模型组相比,各给药组microRNA-24表达显著增高,血清HMGB1水平显著降低(P<0.05),与单药组相比,联合用药组microRNA-24表达显著增高,血清HMGB1水平显著降低(P<0.05)。结论依达拉奉联合川陈皮素治疗脑梗死效果优于单独依达拉奉或川陈皮素,其机制可能与提高microRNA-24表达水平和降低血清HMGB1水平有关。

Objective To investigate the effect of edaravone combined with nobiletin on rats with cerebral infarction and the effects of microRNA-24 and HMGB1.Methods 180 SD male mice were randomly divided into 5 groups:control group,model group,edaravone group,nobiletin group and combined drug group,36 rats in each group.In addition to the control group,the other four groups were constructed with middle artery occlusion(MCAO)model,and were divided into 4 subgroups according to different time points(1,3,5,7 days).Each drug group was intraper-itoneally injected with corresponding drugs.Each subgroup was administered a corresponding time,once a day,and the control group and the model group were injected with an equal volume of 0.9%sodium chloride solution.The neurological deficit scores,brain infarct volume and water content of the rats in each group were compared,and the levels of microRNA-24 and HMGB1 were com-pared.Results The neurological deficit score,brain infarct volume and water content of the model group and each drug-administered group were significantly higher than those of the control group(P<0.05).The neurological deficit score,brain tissue infarction volume and water content in each drug-administered group were significantly lower than those in the model group(P<0.05).The neurological deficit score,brain infarct volume and water content in the combination group were sig-nificantly lower than those in the edaravone group and nobiletin group(P<0.05).Compared with the control group,the expression of microRNA-24 was significantly decreased in the other groups,and the serum HMGB1 level was significantly increased(P<0.05).Compared with the model group,the expression of microRNA-24 was significantly increased in each drug-administered group.The serum HMGBl level was significantly lower(P<0.05).Compared with the single drug group,the expression of microRNA-24 in the combination group was significantly increased,and the serum HMGB1 level was significantly decreased(P<0.05).Conclusion Edaravone combined with nobiletin is superior to edaravone or nobiletin alone in the treatment of cerebral infarction.The mechanism may be related to the increase of microRNA-24 expression level and the decrease of ser-um HMGB1 level.