| Objective: The study of aluminum exposed impact on the expression of Low density lipoprotein receptor-related protein1(LRP-1) receptor and lead to the accumulation of β-amyloid protein(Aβ) by Blood cerebrospinal fluid barrier(BCB) in rat.Methods: Eighty healthy, Male Sprague-Dawley(SD) rats were randomly divided into four groups by weight: control and the treatment groups, received gavage of aluminum lactate at the concentrations of 0, 10, 30, 90 mg/kg for 2 months,respectively. 1. Morris water maze was performed to observe the learning and memory impairment of rats. graphite gurnace atomic absorption spectrometry(GFAAS) detected the aluminum content in brain 、blood and cerebrospinal fluid. 2. we use reagent kit To detect the level of oxidative stress in choroid plexus of rats. 3. The content of Aβ1-40 and Aβ42 in cerebrospinal fluid、blood and choroid plexus were measured by Elisa assays. 4. LRP-1 and Protein kinase C-δ(PKC-δ) protein expression in the choroid plexus were measured using western blot method, and the gene expression level of LRP-1 and its ligand were detemined with RT-PCR.Results : 1.The results of behavioral test showed that: with the increase of training times,the escape latency of aluminum treated rats had statistical significant difference in the Morris water maze tests(P<0.05). Compared with control and low dose groups, the number of times passing through the quadrant where the platform was placed in, in the medium and high dose groups were significantly reduced(P<0.05). 2.The result of the level of oxidative stress showed that: with the increase of exposure dose, choroid plexus tissue was attacked by free radicals degree increases gradually. Compared with control group, the high and middle dose group difference were more serious(P<0.05). Compared with low dose group, the high and middle dose group difference also were more serious(P<0.05). With the increase of exposure dose, the ability to remove free radicals reduced gradually in the choroid plexus organization of rats, and the high dose group compared with control group and low dose group difference was statistically significant(P<0.05). 3.The results of GFAAS detected showed that: with the increase of the infected dose, the aluminum content of each groups infected rats was increased in brain aluminum and CSF(P<0.05)and then the high dose group compared with control, low and medium group were statistically significant in brain(P<0.05). Compared with control group, aluminum exposure doses group of the blood and CSF of the aluminum content in high dose group was increased(P<0.05).In CSF, compared with low dose group, the aluminum content was increased(P<0.05).There was the same result between middle dose group and control group(P<0.05).4.The result of Elisa shows that: with the increase of infected dose, choroid plexus and cerebrospinal fluid in Aβ amount increased, among them Aβ1-42 content increased gradually, and high, middle dose group compared with control group difference was statistically significant in the cerebrospinal fluid,(P<0.05). Between each groups the content of Aβ1-42 there was no statistically significant in blood, Aβ1-40 in the cerebrospinal fluid and plasma no increase gradually and the exposure group compared with control group no statistical difference(P>0.05).In choroid plexus organization, with the increasing of the aluminum dose, the APP protein content gradually increased, then the high dose group compared with control group difference was statistically significant(P<0.05) while there was no the same result between middle and low dose groups. With the increasing of the exposure dose,Aβ1-42 content was increased gradually,and the high and middle dose group compared with control group was statistically increased(P<0.05).Compared with control group, low dose group was increased but no significant(P>0.05).Compared with control group, the content of Aβ1-40 had no statistical significant(P>0.05). 5. The result of western-blot showed that:as infected dose increased, the result of bands became narrow, and the expression of LRP-1 protein expression declined gradually. High dose group compared with control group and the low, middle dose group had a statistically significant(P<0.05).As exposure dose increased, the result of WB became narrow by western blot, and the expression of PKC-δ protein expression decline gradually. High dose group compared with control group had a statistically significance(P<0.05). 6. The results of RT-PCR showed that:with the increase of exposure dose, the gene expression level of LRP-1 and its ligands, apolipoprotein J(Apoj) and transthyretin(TTR), were significantly lowered in Choroid plexus apolipoprotein(P<0.05). Compared with control group, the gene expression levels of LRP-1、Apoj and TTR in high dose group was significant decreased(P<0.05), the LRP-1 gene expression in middle dose group also decreased significantly(P<0.05).Conclusions: 1. The sub-chronic aluminum exposure induce deficits in learning and memory in rats and it may caused by the increased content of aluminum in brain,blood and CSF. 2. The sub-chronic aluminum exposure can cause the increase of the content of Aβ in CSF and blood. Furthermore, the contents of APP and Aβ also increased in CP of rats. 3. The sub-chronic aluminum exposure can decrease the expression level of LRP-1 protein. The gene expression of it and its ligands had the similar results in CP of rats and lead to Aβ accumulating in brain. 4. The sub-chronic aluminum exposure can decrease the expression level of PKC-δ protein.The mechanism of aluminum inhibited of LRP- 1 receptor expression may relate to the activity of PKC-δ protein. |
PDF Full Text Request