Ghrelin对高脂喂养大鼠肝脏氧化应激及Akt/GSK3β信号通路的影响

摘要/Abstract

摘要： 目的探讨Ghrelin对高脂喂养的大鼠肝脏氧化应激水平及Akt/GSK3β信号通路的影响。方法成年雄性Wistar大鼠随机分为正常对照组(NC组)、高脂饮食组(HFD组)和Ghrelin组,每组10只小鼠。NC组给予正常饲料喂养,HFD组及Ghrelin组给予高脂饮食,喂养6周后,进行药物干预4周:Ghrelin组给予Ghrelin(60 μg/kg)每日两次腹腔注射,相应NC组及HFD组给予0.9%氯化钠溶液进行对照;结束后处死大鼠,检测血清丙氨酸氨基转移酶(ALT)、三酰甘油(TG)及总胆固醇(TC);测定肝组织匀浆超氧化物歧化酶(SOD)及丙二醛(MDA);实时 PCR检测肝脏组织Akt、GSK3β mRNA表达的改变。结果 Ghrelin 组大鼠肝脏湿重、血TC及TG均低于HFD组(P<0.05);Ghrelin组与HFD组比较,SOD明显增高(P<0.05),MDA有所降低 (P>0.05);Ghrelin组与HFD组相比,肝脏组织Akt基因mRNA表达升高1.03倍 (P>0.05),GSK3β基因mRNA表达升高3.23倍,(P<0.05)。结论 Ghrelin 能改善高脂喂养大鼠血脂水平,减轻氧化应激损伤,其作用机制可能与Akt/GSK3β信号通路相关。

关键词: Ghrelin, 非酒精性脂肪肝, 高脂饮食, 氧化应激, Akt/GSK3β信号通路

Abstract: Objective To investigate the effect of ghrelin on hepatic oxidative stress and Akt/GSK3β signaling pathway in rats fed with high-fat diet.Methods Male Wistar rats were randomly divided into normal control (NC) group, high-fat diet (HFD) group and ghrelin group (n=10 per group). Rats in NC group were fed with normal diet, while rats in both HFD and ghrelin group were fed with HFD for 6 weeks. Then, rats in NC group and HFD group were treated with saline for 4 weeks, while rats in ghrelin group were injected with ghrelin twice intraperitoneally at dose of 60 μg/kg for 4 weeks. At the end of the experiment, serum levels of alanine aminotransferase (ALT), triglycerides (TG) and total cholesterol (TC) were detected, and superoxide dismutase (SOD) and malondialdehyde (MDA) in liver homogenate were analyzed. Expressions of Akt and GSK3β mRNA in liver were detected using real-time PCR (RT-PCR). Results Wet weight of liver, serum TG and TC in HFD group were obviously higher than those in ghrelin group (P<0.05). Compared with those in HFD group, SOD level was higher (P<0.05) while MDA level was slightly lower (P>0.05) in ghrelin group. Ghrelin treatment enhanced the expression of Akt (P>0.05) and GSK3β (P<0.05).Conclusion Ghrelin could reduce hepatic oxidative stress in HFD-fed rats, which might be related to its effect on Akt/GSK3β pathway.

Key words: Ghrelin, NAFLD, High-fat diet, Oxidative stress, Akt/GSK3β pathway

李文松, 陈立艳, 毕蔓茹, 颜炳柱, 康岚, 杨鹏飞, 王晓韧, 杨宝山. Ghrelin对高脂喂养大鼠肝脏氧化应激及Akt/GSK3β信号通路的影响[J]. 肝脏, 2017, 22(7): 597-601.

LI Wen-song, CHEN Li-yan, BI Man-ru, YAN Bing-zhu, KANG Lan, YANG Peng-fei, WANG Xiao-ren, YANG Bao-shan.. The effects of ghrelin on hepatic oxidative stress and Akt/GSK3β signaling pathway in high-fat diet-fed rats[J]. Chinese Hepatolgy, 2017, 22(7): 597-601.

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