Ac-HF对Aβ_(1-42)致大鼠皮质原代神经元损伤的保护作用及对α分泌酶活性的影响  

Effects of Ac-HF on protection and α-secretase activity of primary cultured rat cortial neurons from the toxic of Aβ_(1-42) peptide

作　　者：奉文尚[1] 赵宇红[1] 王红梅[1] 钟翎[1] 

机构地区：[1]广东药学院药科学院药理教研室,广东广州510224

出　　处：《解剖学研究》2012年第6期406-410,共5页Anatomy Research

基　　金：广东省科技计划项目(2010B060500016)

摘　　要：目的探讨贯叶金丝桃素乙酸酯(hyperforin acetate,Ac-HF)对β淀粉样肽(Aβ)1-42毒性损伤大鼠原代培养大脑皮层神经元的作用及对α分泌酶活性的影响及可能机制。方法采用大鼠原代培养皮层细胞,用MTT法观察Ac-HF对Aβ1-42毒性损伤后的神经细胞活力的影响。用ELASA检测其对α分泌酶活性及可溶性淀粉样前体蛋白(sAPPα)分泌的影响,应用Western blot检其对淀粉样前体蛋白(APP)及解聚金属蛋白酶(a disintegrin and metalloproteinas,ADAM)10表达的影响;并观察Calphostin C(Cal.C)对Ac-HF这些作用的影响。结果 0.1～10.0μmol/L Ac-HF无细胞毒性(P>0.05),1.0～50.0μmol/L Ac-HF可增加Aβ1-42毒性损伤的大鼠皮层神经细胞的活力(P<0.05),0.1～10.0μmol/L Ac-HF可使α分泌酶活性增加,sAPPα分泌增多,对APP蛋白表达无影响,使ADAM10表达增多,PKC抑制剂Calphostin C(Cal.C)可抑制Ac-HF对α分泌酶的活性,sAPPα分泌及ADAM10表达的影响。结论 1.0～10.0μmol/L Ac-HF对Aβ1-42毒性损伤的大鼠皮层神经细胞有保护作用,Ac-HF可通过增加α分泌酶活性及sAPPα分泌产生保护作用,这一作用可能是通过激活PKC通路增加ADAM10表达。Objective To evaluate the effects of hyperforin acetate （Ac-HF） on protection of primary cultured rat cortial neurons from the toxic of β-amyloid 1-42（Aβ1-42） peptide and investigate the effects of Ac-HF on α-secretase activity and the possi- ble mechanisms. Methods With primary culture SD rat cortical neurons, Ac-HF on the activity of neurons was obseved by MTT af- ter toxic injury of 40 μmol/L, activity of α-secretase and secrition of sAPPα were deetected by ELASA, expression of APP and a disintegrin and metalloproteinas （ADAM）10 were decteeted by Western blot, and abserved the effect of the PKC inhibitor Calphostin c （Cal.C） on the Ac-HF. Results In concentration of 1-50 μmol/L Ac-HF increased cell viability injury by toxic Aβ1-42 on rat cor- tical neurons （P〈0.05）. 0. 1-10.0μmol/L Ac-HF was non-cytotoxie （P〉0.05） and which increased activity of α-secretase and se- cretion of sAPPa, increased expression of APP and ADAMIO. Cal. C can inhibit the effect of Ac-HF on activity of α-secretase, sAPPα secretion and expression of ADAM10. Conclusion 1-10 μmol/L Ac-HF has protective effects on rat cortical neuron from toxic Aβ1-42 injury, which due to Ac-HF increasing activity of α-secretase and secretion of sAPPa, this may result from ADAM10 mediated shedding of APP via PKC pathway.

关 键 词：贯叶金丝桃素乙酸酯 α分泌酶 解聚金属蛋白酶10 PKC抑制剂 

分 类 号：R749.16[医药卫生—神经病学与精神病学]