丁苯酞对小鼠脑缺血再灌注损伤保护作用及对MMP-9、TIMP-1及Caspase-3表达的影响

目的探讨丁苯酞对小鼠脑缺血再灌注损伤的影响以及对基质金属蛋白酶9(MMP-9)、基质金属蛋白酶组织抑制因子(TIMP-1)、半胱氨酸蛋白酶-3(Caspase-3)表达水平的影响。方法将54只KM小鼠随机均分为假手术组、模型组、丁苯酞低剂量组(20 mg/kg)、丁苯酞中剂量组(40 mg/kg)、丁苯酞高剂量组(80 mg/kg)。模型组和丁苯酞组采用线栓法制备小鼠脑缺血再灌注损伤模型假手术组同样手术操作但不进行线栓。观察各组小鼠神经功能损伤、脑梗死、脑水肿、氧化应激、炎性反应、脑组织凋亡情况以及MMP-9、TIMP-1表达水平。结果与假手术组比较,模型组、丁苯酞低剂量组、丁苯酞中剂量组、丁苯酞高剂量组小鼠神经功能评分、脑梗死体积百分比、脑组织含水量、细胞凋亡率、伊文思蓝(EB)、丙二醛(MDA)、一氧化氮(NO)、肿瘤坏死因子α(TNF-α)、Caspase-3、Bax蛋白水平、MMP-9、TIMP-1相对表达量明显升高(P <0.05),超氧化物歧化酶(SOD)活性、Bcl-2蛋白水平明显降低(P<0.05);与模型比较,丁苯酞低剂量组、丁苯酞中剂量组、丁苯酞高剂量组小鼠神经功能评分、脑梗死体积百分比、脑组织含水量、细胞凋亡率、EB、MDA、NO、TNF-α、Caspase-3、Bax蛋白水平、MMP-9相对表达量明显降低(P<0.05),SOD活性、Bcl-2蛋白水平、TIMP-1相对表达量明显升高(P <0.05),呈剂量依赖性。结论丁苯酞对小鼠脑缺血再灌注脑损伤有保护作用,可能与调节小鼠脑组织氧化应激、细胞凋亡以及血脑屏障有关。

Protective effect of butylphthalide on cerebral ischemia-reperfusion injury in mice and its influences on expression of MMP-9,TIMP-1 and Caspase-3

Objective To explore effects of butylphthalide on cerebral ischemia-reperfusion injury(CIRI) in mice and its influences on expression levels of matrix metalloproteinase 9(MMP-9),tissue inhibitor of metalloproteinase(TIMP-1) and cysteine protease-3(Caspase-3).Methods A total of 54 KM mice were randomly divided into sham operation group,model group,low-dose butylphthalide group(20 mg/kg),middle-dose butylphthalide group(40 mg/kg) and high-dose butylphthalide group(80 mg/kg).CIRI models were prepared by suture method.The nerve function injury,cerebral infarction,cerebral edema,oxidative stress,inflammatory reactions,brain tissue apoptosis and ex?pression levels of MMP-9 and TIMP-1 in each group were observed.Results Compared with sham operation group,score of nerve function,percentage of cerebral infarction volume,water content in brain tissue,apoptosis,levels of EB,MDA,NO,TNF-a,Caspase-3 and Bax protein,relative expression quantities of MMP-9 and TIMP-1 were increased in model group,low-dose,middle-dose and high-dose butylphthalide group(P <0.05),while SOD activity and level of Bel-2 protein were decreased(P <0.05).Compared with model group,score of nerve function,percentage of cerebral infarction volume,water content in brain tissue,apoptosis,levels of EB,MDA,NO,TNF-a,Caspase-3 and Bax protein,relative expression quantity of MMP-9 were decreased in low-dose,middle-dose and high-dose butylphthalide group(P<0.05),while SOD activity,level of Bel-2 protein and relative expression quantity of TIMP-1 were increased(P <0.05).Conclusion Butylphthalide can protect CIRI in mice,which may be related to regulating oxidative stress,apoptosis and blood-brain barrier in brain tissue.