Influence Of Triptolide On Drebrin And Cofilin Expression In The Hippocampus Of Rats After Injection Of β-amyloid

Objective:Although the exact cause of Alzheimer’s disease (AD) remains unclear, itspathogenesis is thought to involve neuroinflammation. Triptolide has anti-inflammatory and immunosuppressive activities. Increasing evidence has shown thattriptolide can exert neuroprotective effects. Our previous study suggested thattriptolide can relieve the degeneration of dendritic spines in hippocampal neurons inAD model rats. The cytoskeleton of dendritic spines is composed primarily of actinfilaments. Changes in dendritic spine morphology depend on the reorganisation of theactin cytoskeleton. This latter is mainly regulated by actin-binding proteins. Amongactin-binding proteins, drebrin and cofilin have important influence on spinemorphogenesis by regulating the actin cytoskeleton. In the present study, we observedthe effects of triptolide on drebrin and cofilin expressions in the hippocampus of ADmodel rats. The aim of this study is to explore the action mechanism of triptolideagainst AD from the angle of the remodeling of dendritic spines.Methods:1．Forty-five male SD rats were equally divided into control group, model groupand triptolide-treated group.The AD model group was established with unilateralinjection of beta-amyloid protein(Aβ)1-40into hippocampus in rats. The control groupwas established with unilateral injection of normal saline into hippocampus in rats.The triptolide-treated group rats were administered triptolide(0.4mg/kg.d)intraperitoneally for15days after injection of aggregated Aβ1-40into hippocampus.2．Spine density of hippocampal neurons in each group was assayed by Golgistaining.3．Drebrin and cofilin expressions of hippocampal neurons in each group wereassayed by immunohistochemical staining.4. Drebrin and cofilin mRNA expressions of hippocampal neurons in each group were assayed by RT-PCR.Results:1．Golgi staining results showed that spine density of hippocampal neurons inthe model group was decreased as compared with the control group (P <0.01) andthat spine density of hippocampal neurons in the triptolide-treated group wasincreased as compared with the model group (P<0.05).2．Drebrin immunohistochemical staining results showed that the cell numberand average optical density of drebrin positive staining in the model group weredecreased compared to the control group(P <0.01) and that the cell number of drebrinpositive staining in the triptolide-treated group was increased compared to the modelgroup(P <0.05).3．Cofilin immunohistochemical staining results showed that the cell number andaverage optical density of cofilin positive staining in the model group were increasedcompared to the control group(P<0.01) and that the cell number and average opticaldensity of cofilin positive staining in the triptolide-treated group were decreasedcompared to the model group(P＜0.05or P <0.01).4. Drebrin RT-PCR results showed that the mRNA expression of drebrin in themodel group was decreased compared to the control group（P＜0.01）and the mRNAexpression of drebrin in the triptolide-treated group was increased compared to themodel group（P＜0.05）.5．Cofilin RT-PCR results showed that the mRNA expression of cofilin in themodel group was increased compared to the control group（P＜0.01） and the mRNAexpression of cofilin in the triptolide-treated group was decreased compared to themodel group（P＜0.01）.Conclusions:Triptolide can increase drebrin expression in the hippocampus of AD model ratsand inhibit cofilin expression in the hippocampus of AD model rats.