职业铝接触工人认知功能的改变及血浆中CDK5与磷酸化tau蛋白的关系

Changes in Cognitive Function and Relationship Between CDK5 and Phosphorylated Tau Protein in Plasma in Workers Exposed to Aluminum

[目的]观察职业铝接触工人认知功能的改变以及血浆中细胞周期依赖性蛋白激酶5(CDK5)与磷酸化tau蛋白的关系。[方法]采用整群抽样法,抽取山西某铝厂418例职业铝接触男性工人作为研究对象。采用简短精神状态量表(MMSE)、数字广度实验(DS)、物体记忆实验(FOM)、简单反应时(SRTT)等问卷测试工人的认知功能。收集工人空腹静脉血样进行实验室分析,石墨炉原子吸收分光光度法检测血浆铝含量;应用ELISA法测定血浆中磷酸化tau-181蛋白(P-tau181)、磷酸化tau-231蛋白(P-tau231)和CDK5蛋白的含量。[结果]根据血铝浓度P25和P75将研究对象分为3组:低血铝组[(64.00±17.78)μg/L]、中血铝组[(132.59±27.45)μg/L]和高血铝组[(244.45±69.86)μg/L]。认知功能测试结果显示,不同血铝水平工人MMSE、DS、FOM、SRTT测试结果不相同(均P<0.05)。蛋白测定结果显示,与低血铝组相比,高血铝组P-tau181、P-tau231浓度增高,中血铝组、高血铝组CDK5浓度增高(P<0.05)。相关分析显示,P-tau181与MMSE、DS、FOM均存在负相关(r=-0.308,-0.285,-0.252;均P<0.05);P-tau231与MMSE、DS存在负相关(r=-0.326,-0.291;均P<0.05),与SRTT存在正相关(r=0.257,P=0.050);P-tau181和P-tau231与CDK5均呈正相关(r=0.327,0.253;均P<0.05)。[结论]职业铝接触导致的认知功能改变与磷酸化tau蛋白有关;作业工人CDK5表达与tau蛋白磷酸化有关,CDK5可能参与铝致tau蛋白磷酸化过程。

[ Objective ] To observe the changes in cognitive function and the relationship between cyclin-dependent kinase 5 （CDK5） and phospborylated tau protein in plasma in workers exposed to aluminum. [ Methods ] A cross-sectional study with cluster sampling was designed to collect 418 male workers from an aluminum plant. Mini mental state examination （MMSE）, digit span （DS）, fuld object memory evaluation （FOM）, and simple reaction time test （SRTT） were used to assess their cognitive function. Fasting venous blood samples of the workers were collected and analyzed by graphite furnace atomic absorption spectrometry to test blood aluminum content. ELISA was used to determine the expression levels of phosphorylated tau 181 （P-tau 181）, phosphorylated tau 231 （P-tau231）, and CDK5 in plasma. I Results ] The subjects were divided into three groups according to the P25 and P75 values of blood aluminum levels： low [（64.00 ± 17.78）μg/L], middle [（132.59 ± 27.45）μg/L], and high [（244.45± 69.86）μg/L] blood aluminum groups. The cognitive function tests showed that the result differences of MMSE, DS, FOM, and SRTT among the three groups were statistically significant （all Ps 〈 0.05）. The protein determination showed that, compared with the low blood aluminum group, the P-taul81 and P-tau231 levels were significantly higher in the high blood aluminum group, and the levels of CDK5 were significantly increased in the high blood aluminum group and the middle blood aluminum group （P〈0.05）. It was found that P-taul81 was negatively correlated with MMSE, DS, and FOM （r=--0.308, -0.285, -0.252; all Ps 〈 0.05）, P-tau231 was negatively correlated with MMSE and DS （r=-0.326, -0.291; both Ps 〈 0.05） and positively correlated with SRTT （r=0.257, P=0.050）; P-taul81 and P-tau231 were positively correlated with CDK5 （r=-0.327, 0.253; both Ps 〈 0.05）. [ Conclusion ] The changes of cognitive function induced by occupational aluminum exposure are associated with phosphorylated tan. The expression of CDK5 in workers is related to the phosphorylation of tau, and CDK5 may be involved in aluminum-induced tan protein phosphorylation.