Abstract:

Objective To observe the effect of Tenuigenin (TEN) on low density lipoprotein receptor-related protein 1（LRP1）level in Alzheimer’s disease (AD) rat hippocampus. Methods Sixty SD rats were randomly divided into groups respectively. β-Amyloid protein (Aβ)_1-40 was injected into hippocampus CA1 region to establish AD model by brain stereotactic technique and then rats were treated with intragastric TEN for four weeks. Learning and memory abilities were assessed by Morris water maze and the Real-time PCR and Western blotting were used to analysis the expression of LRP1 mRNA and protein. The changes of LRP1 positive neurons were checked by immunofluorescence staining. Results 1. Morris water maze: the learning and memory ability of the AD group was significantly decreased than that of the normal group（P<0.01）.After TEN gastric lavage treatment, the escape latency was shortened, the swimming distance was reduced, and the frequency of the virtual platform was increased in every TEN treatment group, there were a statistically significant difference in middle and high dose group（P<0.05 or P<0.01）. 2. Real-time PCR and Western blotting: the relative expression levels of LRP1 mRNA and protein in AD group were significantly lower than that in normal control group (P<0.01). After TEN treatments, the relative expression of LRP1 mRNA and protein in the treatment group increased gradually with the increase of the dosage of TEN. The effect of low dose group was not significant (P>0.05), but there were a significant difference between middle and high dose groups (P<0.01). 3. Compared with normal group, the number of LRP1 positive cells in the AD group decreased significantly (P<0.01), but in the high dose group increased significantly (P>0.05). Conclusion TEN may improve the learning and memory ability of Aβ _1-40induced AD rats by increasing the content of LRP1 in the brain.

Key words: Tenuigenin, Alzheimer’s disease, β\, Amyloid protein _1-40, Hippocampus,  , Real-time PCR, Rat