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基于PPARs/L-FABP通路的荔枝皮多酚提取物治疗NAFLD的作用机制研究
结题报告
批准号:
81960674
项目类别:
地区科学基金项目
资助金额:
34.0 万元
负责人:
杨子明
学科分类:
代谢性疾病药物药理
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
杨子明
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中文摘要
荔枝皮富含多酚类成分,有极高的经济价值。根据前期在定量蛋白质组学研究的成果,荔枝皮多酚提取物治疗非酒精性脂肪肝(NAFLD)的机制可能与PPARs/L-FABP通路有关,本项目拟在动物与细胞模型上研究其治疗NAFLD的作用机制。在高脂饮食诱导的NAFLD小鼠模型上,揭示出荔枝皮多酚提取物是如何通过PPARs/L-FABP通路降低脂肪酸摄入,抑制甘油三酯生成,诱导甘油三酯降解,加速胆汁酸生成从而达到治疗NAFLD的目的。在shRNA慢病毒建立的L-FABP基因敲减小鼠身上,揭示出荔枝皮多酚提取物是否通过抑制小肠L-FABP的表达,减少长链脂肪酸的摄入,达到降低体内脂肪酸的作用。在感染siRNA慢病毒的脂肪变性HepG2细胞模型上,揭示出荔枝皮多酚提取物是否是PPARs的激动剂及哪种亚型的激动剂。从而阐明荔枝皮多酚提取物治疗NAFLD的作用机制,找到其作用靶点,为进一步开发提供理论依据。
英文摘要
Research has shown that litchi pericarp is rich in polyphenols and are very hight economic value. According to the results of quantitative proteomics studies, the mechanism of litchi pericarp polyphenol extract in the treatment of non-alcoholic fatty liver disease (NAFLD) may be related to the PPARs/L-FABP pathway. In this study, we intend to verify its mechanisms in animal and cell models. In the NAFLD model of mice induced by high fat diet, the litchi pericarp polyphenol extract can reduce the intake of exogenous fatty acid and cholesterol, inhibit the generation of hepatic triglyceride, induce the degradation of the liver triglyceride, and accelerate the generation of the liver bile acid. The mechanism of the treatment of NAFLD by the polyphenol extract of litchi pericarp is the regulation of the PPARs/ L-FABP pathway. L-FABP gene knockout mice were established by shRNA lentivirus. In gene knockout mice, we studied polyphenol extract of litchi pericarp could reduce the intake of long-chain fatty acids and reducing fatty acids in vivo by inhibiting the expression of L-FABP in small intestine. In the steatosis HepG2 cell model, siRNA was used to silence the expression of PPARα, PPARβ and PPARγ respectively. The effects of polyphenol extract of litchi pericarpl on lipid regulation and PPARs mediated signal transduction pathway were observed. It was revealed that the polyphenol extract of litchi pericarp was a agonist of PPARs and which subtype of agonist. Our study will clarify the mechanism of litchi pericarp polyphenol extract in the treatment of NAFLD. Ours research hava important implications for the promotion of litchi consumption, functional food deep processing and litchi industry sustainable development.
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DOI:10.3390/antiox12101848
发表时间:2023-10-12
期刊:Antioxidants (Basel, Switzerland)
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DOI:10.3390/agronomy13030637
发表时间:2023-03-01
期刊:AGRONOMY-BASEL
影响因子:3.7
作者:Yang,Ziming;Li,Wei;Chan,Albert S. C.
通讯作者:Chan,Albert S. C.
DOI:10.3390/foods11233837
发表时间:2022-11-28
期刊:Foods (Basel, Switzerland)
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DOI:--
发表时间:2022
期刊:广西植物
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作者:杨子明;张利;刘金磊;李典鹏
通讯作者:李典鹏
国内基金
海外基金