z-DEVD-fmk对甲基苯丙胺依赖大鼠脑海马组织caspase-3活性及其蛋白表达的影响

Effect of z-DEVD-fmk on caspase-3 Activity and Its Protein Expression in Brain Tissues of Methamphetamine-dependent Rats

目的:观察z-DEVD-fmk(caspase-3抑制剂)对甲基苯丙胺(methamphetamine,MA)依赖大鼠海马组织caspase-3活性及其蛋白表达的影响。方法:选取健康Wistar大鼠40只,随机分为空白对照组、MA依赖组、MA+z-DEVD-fmk干预组和z-DEVD-fmk组,各10只。参考文献建立MA依赖大鼠实验动物模型,经侧脑室注射z-DEVD-fmk干预治疗,采用酶标仪法检测caspase-3活性,采用免疫组化法检测Caspase-3蛋白的表达。结果:与空白对照组比较,MA依赖组和MA+zDEVD-fmk干预组海马组织caspase-3活性明显升高(P<0.01),Caspase-3蛋白表达增多(P<0.01);与MA依赖组比较,Ma+z-DEVD-fmk干预组caspase-3活性明显降低(P<0.05),Caspase-3蛋白表达减少(P<0.05)。结论:z-DEVD-fmk能够抑制MA依赖大鼠海马组织caspase-3活性,降低Caspase-3蛋白表达,z-DEVD-fmk具有干预与保护MA致大鼠脑组织损伤作用。

Objective： To observe the effect of z-DEVD-fmk （caspase-3 inhibitor） on caspase-3 activity and its protein expression in brain tissue of methamphetamine （MA） -dependent rats. Methods： A total of 40 Wistar rats were randomly divided into the blank control group, MA-dependent group, MA ＋ z-DEVD-fmk group and z-DEVD-fmk group, each group had 10 rats. The experimental animal model of MA-dependent was established according to reference. After intracerebroventricular injection of z-DEVD-fmk intervention, microplate assay was used to determine the caspasc-3 activity. Immunohistochemistry method was used to detect the expression of Caspase-3 protein. Results： Compared with the blank control group, caspase-3 activity in brain tissue of MA-dependent group and MA ＋ z-DEVD-fmk intervention group significantly increased, while Caspase-3 protein expression also increased （ P 〈 0. 01 ）. Compared with MA-dependent group, caspase-3 activity decreased and Caspase-3 protein expression also decreased in MA ＋ z-DEVD-fmk intervention group （ P 〈 0.05 ）. Conclusions ： z-DEVD-fmk can inhibit caspase-3 activity and expression of Caspase-3 protein in brain tissue of MA-dependent rats, which indicates that z-DEVD-fmk can prevent rats from brain damage induced by MA.