麝香酮对大鼠创伤性脑损伤后早期MMP9蛋白表达的影响

摘要

目的 观察麝香酮对大鼠早期创伤性脑损伤(TBI)MMP9蛋白表达的影响,探寻麝香酮神经保护作用的机制.方法 选择SD大鼠160只,按照简单随机化方法分为正常组、假手术组、TBI创伤组、麝香酮组(0.9 mg/kg)组各40只.每组在12h、24 h,3d、7d各10只.采用液压打击法制造大鼠TBI模型,假手术组只开骨窗,麝香酮组致伤后即刻及每天腹腔内注射麝香酮,TBI创伤组相同时间点腹腔内注射等量等渗的0.9％氯化钠注射液.各个时间点分别采用避暗实验观察伤后各组大鼠学习记忆能力、HE染色观察脑组织形态改变、Westernblot观察MMP9蛋白表达情况.结果 大鼠伤后开始出现学习记忆力下降,脑组织形态改变,MMP9蛋白表达增高,并在3d左右达到高峰,7d后逐渐减轻.与正常组及假手术组比较,TBI创伤组学习记忆力下降、MMP9蛋白表达增高;与TBI创伤组比较,麝香酮组12d、24 h,3d、7d各个时间点大鼠避暗试验结果提示学习记忆力显著提高、脑组织形态改变较弱,MMP9蛋白表达下降(均P＜0.05).结论 对于大鼠早期TBI,麝香酮可能是通过减少MMP9蛋白表达改善大鼠学习记忆能力.%Objective:To investigate the effect of muscone on the expression of MMP9 protein in early traumatic brain injury (TBI) in rats and to explore the mechanism of neuroprotective effect of muscone.Methods:160 SD rats were randomly divided into the normal group,the sham group,TBI group and muscone(0.9 mg/kg) group,with 40 rats per group.Each group included 10 rats at four different time points (12 h,24 h,3 d,7 d).Left-sided fluid percussion TBI models were utilized in the study.Sham rats underwent craniotomy only.Rats in muscone group received intraperitoneal injection of muscone immediately and then every day after injury.Instead,equal volume of saline was used in TBI group.The learning and memory ability of rats in each group after injury was observed at all time points with step-through test,and the changes of brain tissue morphology were observed by HE staining.MMP9 expression were observed after injury with Westernblot.Results:After injury in rats,learning and memory ability was reduced;brain tissue morphology changed,and MMP9 expression rose,reached the peak at 3d and decreased at 7d.Compared with the normal group and the sham operation group,the learning and memory ability of TBI group was decreased and the expression of MMP9 protein was increased.Compared with TBI group,step-through tests in muscone group at different time points(12 h,24 h,3 d and 7 d) showed that the learning and memory ability was significantly improved,the morphology of brain tissue was weaker,and the expression of MMP9 protein decreased.Conclusion:In the early stage of TBI,muscone may improve the learning and memory ability of rats by reducing the expression of MMP9 protein.