海洛因成瘾复吸大鼠额叶皮质区Tau蛋白磷酸化、PHF、PKA的改变

The change of Tau phosphorylation、PHF and PKA at the frontal lobe cortex in heroin addicted and readdicted rats

目的:模仿人类吸毒成瘾方式建立海洛因成瘾复吸动物模型,探讨其脑额叶皮质区Tau蛋白磷酸化及成对螺旋纤维细丝(paired helical filaments,PHF)形成的问题,并通过检测环腺苷酸依赖性蛋白激酶(cyclic a-denosine monophosphate dependent protein kinase,PKA)的改变探讨其发生的原因,为海洛因成瘾复吸致脑损伤的机制研究提供参考依据。方法:采用吸毒成瘾、治疗、复吸成瘾、再治疗、再复吸成瘾的方法建立海洛因成瘾复吸动物模型,设立对照组和模型组,取大鼠脑额叶皮质区组织,用组织免疫印迹检测Tau蛋白在Ser 396位点磷酸化水平以及PHF-1、PKA-α、PKA-β的表达水平。结果:模型组Tau蛋白在Ser396位点磷酸化水平较对照组增高(P<0.05),对应位点PHF的形成也相应增多(P<0.01),同时模型组PKA-α、PKA-β表达水平均较对照组增高(P<0.05)。结论:在海洛因成瘾复吸大鼠脑额叶皮质区出现Tau蛋白过度磷酸化和PHF的形成,且Tau蛋白过度磷酸化与PKA表达水平的提高有关。

Objective：To make the animal model of heroin addiction and readdiction by imitating the processes of human heroin addiction and study the phosphorylational Tau,the formation of paired helical filaments（PHF） and the mechanism in the frontal lobe cortex by detecting the level of cyclic adenosine monophosphate dependent protein kinase（PKA）,which will give a reference to the mechanism and treatment of brain damage induced by heroin addiction and readdiction.Methods：Established the animal model of heroin addiction and readdiction by the processes of human heroin addiction,abstention treatment to heroin readdiction,reabstention treatment to heroin readdiction and third readdiction,rats were randomly divided into control group and model group.Detected the levels of Tau protein phosphorylation at Ser 396 site,PHF-1,PKA-α and PKA-β by Western Blot in the frontal lobe cortex of brain tissue.Results：By contrast,the level of Tau protein phosphorylation at Ser 396 site was increased.The formation of PHF and the levels of PKA-α and PKA-βwere all increased.Conclusion：Tau hyperphosphorylation and PHF were formed in the frontal lobe cortex of brain tissue of heroin addicted and readdicted rats,which was associated with the rise of PKA