浙江医学2017，Vol.39Issue(12)：952-956,960,6.DOI:10.12056/j.issn.1006-2785.2017.39.12.2016-1784
生酮饮食对癫痫大鼠海马的保护作用及机制研究
Ketogenic diet attenuates hippocampua injury in pentylenetetrazol-kindled seizure and its relation to mammalian target of rapamycin pathway suppression in rats
摘要
Abstract
Objective To investigate the effect of ketogenic diet on hippocampus injury in pentylenetetrazol-kindled seizure and its relation to mammalian target of rapamycine (mTOR) pathway in rats.Methods The PTZ-kindled seizure model was induced by intra-ventricular infusion of 35mg/kg pentylenetetrazol (PTZ) in male Sprague-Dawley (SD) rats.Forty four rats,in which the seizure was fully kindled,were divided into 4 groups with 11 rats in each group.Rats in ND+PTZ and ND+PTZ+RAP groups were fed with normal diet,while those in KD+PTZ and KD+PTZ+RAP were fed with ketogenic diet.The mTOR pathway inhibitor rapamycin(RAP) was given to rats in ND+PTZ+RAP and KD+PTZ+RAP groups by intra-ventricular infusion 30min before PTZ injection.The seizure stages and the neuron in hippocampal CA1,CA3 and DG regions were counted.And the expressions of pS6,S6,pAkt,Akt,pAMPK and AMPK were detected by Western blot.Results The seizure stage of the kindled rats in the KD+PTZ group was lower than that of ND+PTZ group significantly (P＜0.05).The stages of KD+PTZ+RAP group were lower than those of ND+PTZ and ND+PTZ+RAP groups significantly (P＜0.05).The density of neuron in hippocampal CA1 subarea in KD+PTZ group was higher than ND+PTZ group significantly (P＜0.05),and the density of KD+PTZ+RAP was higher than ND+PTZ+RAP group (P＜0.05).Additionally,the density of ND+PTZ+RAP was higher than ND+PTZ (P＜0.05).Western blot result shows that the expression of phosphor-S6 to total S6(pS6/S6) and phosphor-Akt to total Akt(pAkt/Akt) was increased in ND+PTZ group compared to control (P＜0.05).The expression levels of phosphor-AMPK to total AMPK (pAMPK/AMPK) in all kindled groups were higher than those of non-kindled control groups (P＜0.05).Compared to the ND+PTZ group,the expression levels of pS6/S6 and pAkt/Akt were decreased (P＜0.05),while the pAMPK/AMPK was increased in KD+PTZ group (P＜0.05).Compared to the KD+PTZ group,the expression of pS6/S6 and pAkt/Akt in KD+PTZ+RAP group were decreased (P＜0.05).Similarly,compared to the ND+PTZ group,the expression of pS6/S6 and pAkt/Akt in ND+PTZ+RAP group was also significantly decreased (P＜0.05).Moreover,compared to ND+PTZ+RAP,the expression level of pS6/S6 in KD+PTZ+RAP group was decreased significantly (P＜0.05),while the expression level of pAMPK/AMPK was increased (P＜0.05).Conclusion Our study indicated that ketogenic diet has the anti-seizure and neuronal protective effect in PTZ kindled rat model,which may be related to the mTOR pathway suppression.Moreover,the mTOR pathway is modulated by both the inhibition of Akt and activation of AMPK pathway.关键词
生酮饮食/哺乳动物雷帕霉素钯蛋白信号通路/癫痫/海马/神经保护Key words
Ketogenic diet/mTOR signaling pathway/Seizure/Hippocampus/Neuroprotection引用本文复制引用
蒋艳,王宝辉,贾濛濛,卢裕强,裘涛,章正祥,侯群..生酮饮食对癫痫大鼠海马的保护作用及机制研究[J].浙江医学,2017,39(12):952-956,960,6.基金项目
国家自然科学基金项目(81301113、81302938) （81301113、81302938）
浙江省自然科学基金项目(LY16H270002) （LY16H270002）
