Exendin-4 对糖尿病脑缺血再灌注大鼠脑组织中MMP-9 表达的影响

目的:通过观察Exendin-4对糖尿病大鼠脑缺血再灌注后脑梗死体积百分比及脑组织中金属基质蛋白酶-9及基质金属蛋白酶抑制剂-1的变化,探讨Exendin-4对糖尿病大鼠脑缺血再灌注损伤的保护作用机制。方法:选用SD大鼠,给予链脲佐菌素(streptozocin,STZ)建立糖尿病大鼠模型后,随机分为A组:糖尿病对照组(n=6);B组:模型组(n=6);C组:Exendin-4低剂量组(n=6);D组:Exendin-4中剂量组(n=6);E组:Exendin-4高剂量组(n=6)。常规喂养6周后,A组给予假手术处理,B、C、D及E组采用线栓法制作大鼠大脑中动脉缺血90 min再灌注模型,24 h后处死大鼠取脑组织,采用2,3,5一氯化三苯四唑(2,3,5-triphenyltetrazolium chloride,TTC)染色测算脑梗死体积百分比;同时分别采用Western Blot法及RT-PCR测量脑组织中的MMP-9及TIMP-1表达量。结果:脑缺血再灌注能致脑组织中MMP-9及TIMP-1表达量增高,各组与A组比较,有显著差异(P<0.05);给予Exendin-4处理后脑组织中MMP-9及TIMP-1表达增高程度及脑梗死体积百分比明显降低,与B组比较有显著差异(P<0.05)。结论:Exendin-4对糖尿病大鼠脑缺血再灌注损伤有保护作用,其机制可能与抑制MMP-9及TIMP-1的表达有关。

Effect of Exendin-4 on Expression of Brain Tissue MMP-9 After Cerebra Ischemia-reperfusion Injury in Diabetic Rats

Objective: To investigate the protective mechanism of Exendin-4 against cerebral ischemia-reperfusion induced injury in diabetic rats.Methods: The rat model of diabetes mellitus was set up by streptozocin(STZ).The diabetic SD rats were randomly divivded into five groups: diabetes control group(Group A,n=6),model group(Group B n=6),Exendin-4 low-dose group(Group C n=6),Exendin-4 moderate-dose group(Group D n=6),Exendin-4 high-dose group(Group E n=6).Group A was subjected to a sham operation,and other groups were subjected to left middle cerebral artery occlusion for 90 minutes after all rats fed by normal diet six weeks.All rats were killed 24 hours after postoperation,and brain tissue was obtained.The effects of Exendin-4 on the brain was analyzed by detecting the infarct volume and the expression of MMP-9,TIIP-1 through 2,3,5-triphenyltetrazolium chloride(TTC)staining,Western Blot and RT-PCR.Results: Cerebral ischemia-reperfusion injury can increase the expression of brain tissue MMP-9 and TIMP-1.The expression of MMP-9,TIIP-1 increased significantly in Group B,Group C,Group D and Group E,compared with that in Group A(P<0.05).The expression of MMP-9,TIIP-1 reduced significantly in Exendin-4 treatment group,compared with that in Group B(P<0.05).Conclusion: Exendin-4 protect against cerebral ischemia-reperfusion induced injury in diabetic rats,and the mechanism may be related with the inhibition of the MMP-9 and TIMP-1expression.