[Effect of Heixiaoyao Powder on Hippocampal Gene Expression Profile of Alzheimer's Disease Rats]

Objective To observe the effect of Heixiaoyao Powder (HP) on gene microarray profile of hippocampus in Aβ₂₃₋₃₅ fragments induced Alzheimer's disease rat model. Methods Female SD rats were chosen to establish AD model by injecting Aβ₂₅₋₃₅ amyloid into hippocampus ,and then they were divid- ed into 6 groups, i.e., the sham-operation group, the model group,the Western medicine (WM) group, high, middle, and low dose HP groups, 14 in each group. After 7 days of modeling, all rats were administered with respective solution at the daily dose of 3 mL/kg by gastrogavage for 28 successive days. Normal saline was administered to rats in the sham-operation group and the model group. Huperzine A Tablets wa- ter solution was administered to rats in the WM group at the daily dose of 0. 02 mL/kg. HP at the daily dose of 4. 25, 8. 50, 17. 00 g/kg was administered to rats in the low, middle, high HP groups. All rats were sacri- ficed after ending gastrogavage, and their hippocampal tissues were collected to extract tissue RNA. Rat gene microarray was used to screen differentially expressed genes, and then differentially expressed genes with partial dose-dependently changing obtained by microarry were verified by qRT-PCR. Results Compared with the sham-operation group, 538 genes were up-regulated, and 579 genes were down-regulated in the model group. mRNA expressions of wisp1 , crebbp, igfbp-1 , znf483, zfp37, and zic4 increased, while mRNA expressions of casq2 and bcl-2 decreased in the model group (P <0. 05). Compared with the model group, 276 genes were up-regulated, and 170 genes were down-regulated in the 3 HP groups. Of them, 71 up-regulated genes dose-dependently and 70 down-regulated genes dose-dependently. mRNA expressions of igfbp-1 , znf483, zfp37, and zic4 decreased, while mRNA expressions of casq2 and bcl-2 in- creased in the WM group (P <0. 01). mRNA expressions of wisp1 , crebbp, igfbp-1 , znf483, zfp37, and zic4 decreased, while mRNA expressions of casq2 and bcl-2 increased in the high dose HP group (P <0. 01). mRNA expressions of crebbp, igfbp-1, znf483, zfp37, and zic4 decreased (P <0. 01, P <0. 05), while mR- NA expressions of casq2 and bcl-2 increased in the middle dose HP group (P <0. 01, P <0. 05). mRNA ex- pressions of igfbp-1 , znf483, zfp37, and zic4 decreased in the low dose HP group (P <0. 01). Compared with the middle dose HP group, mRNA expressions of crebbp, zfp37, and zic4 increased (P <0.01) , mR- NA expressions of igfbp-1 and bcl-2 decreased in the middle dose HP group (P <0. 01, P <0. 05); mRNA expressions of crebbp, znf483, and zfp37 increased (P <0. 01, P <0. 05), mRNA expressions of igfbp-1, zic4, and bcl-2 decreased in the low dose HP group (P <0. 01). Compared with the middle HP group, mRNA expressions of casq2, zic4, and bcl-2 decreased in the low dose HP group (P <0. 01, P <0. 05). Conclusion HP could affect the occurrence of AD by regulating mRNA expressions of zfp37, znf483, and zic4, and af- fect the metabolism of Aβ and abnormal phosphorylation of Tau protein by inhibiting wnt signal pathway re- lated genes such as wisp-1 , crebbp, igfbp-1 , and casq2.