The Experimental Study Of Rh-bFGF And Nerve Cell Apoptosis Related Genes In Dementia Brain

OBJECTIVE:By Studying the effects of rh-bFGF on the hippocampal neurons on this condition that P -amyloid was added in vitro and in vivo, the inhibitive effects of rh-bFGF on nerve cell apoptosis and perspective therapeutic effects of rh-bFGF on AD may be discovered.METHODS:AD-like neuron model was established through the primary cultured fetal rat hippocampal neurons treated with aggregated P -amyloid peptide fragment 25-35(A P 25-35), and AD rat model established by injecting aggregated A 3 25-35 into the cerebroventricles of SD rats, the experimental groups were injected rh-bFGF solution in the maintime when A 3 25-35 was injected. In vitro, Gimea's, Hoechst33258 stainning were used to study the morphologic changes, Annexin-V and FCM used to detect the apoptotic rate, Agarose gel electrophoresed Assay used to analysis DNA ladder, Western-blot used to investigate the expression of apoptosis related gene. In vivo, Morris Water Maze Test was used to evaluate the changes of rats' spatial memory acquisition, immunohistochemistry Assay used to detect the expression of apoptosis related genes, HE staining used to measure the morphologic changes of apoptotic neurons in rat brain.RESULTS:! in vitro, l)rh-bFGF improved the morphologic changes induced by A 3 25-35;2)rh-bFGF inhibited the DNA ladder and reduced apoptotic rates; 3)rh-bFGF up-regulated the expression of Bcl-2 and down-regulated the expression of Bax/ICE. 2 in vivo, 1) The rats with AD model showed longer latency(PPLs) than normal rats in place navigation test (P<0.001).There was significant difference between expirimantal and control groups; There was significant difference in swimming distance percentage(SDP) of platform quadrant in spatial probe test between rh-bFGF group and model group.2) rh-bFGF improved the morphologic changes in rat brain.3) rh-bFGF up-regulated the expression of Bcl-2 and down-regulated the expression of Bax/ICE.CONCLUSION:The result showed that rh-bFGF could inhibit the neurotoxity of A 25-35 to neurons and modulate learning and memory of dementia rats. rh-bFGF may be put forward as a potential therapeutic agent of AD by regulating the expression of the apoptosis-related gene Bcl-2, Bax, ICE.