Atherosclerosis is driven both by hyperlipidemia and inflammation. Chitin oligosaccharides(NACOS) have shown pharmacological effects on multiple diseases via hypolipidemic and/or anti-inflammatory activities. The pres...Atherosclerosis is driven both by hyperlipidemia and inflammation. Chitin oligosaccharides(NACOS) have shown pharmacological effects on multiple diseases via hypolipidemic and/or anti-inflammatory activities. The present study aims to evaluate whether NACOS treatment can prevent atherosclerosis induced by a highfat-diet(HFD) in Apolipoprotein E-knockout(Apo E;) mice. Results showed that 300 and 900 mg/kg b.w./day NACOS supplementation for 14 weeks significantly decreased atherosclerotic lesions up to 45% and 67% in compared with the HFD(P < 0.05), as measured in the valve area of the aortic root. Further, NACOS supplementation significantly reduced the serum hyperlipidemia and circulating proinflammatory cytokines including interleukin-1β, interleukin-6, monocyte chemoattractant protein-1 and tumor necrosis factor-α. NACOS decreased the hepatic Hmgcr to reduce cholesterol synthesis, activated the genes involved in reverse cholesterol transport to enhance cholesterol efflux and excretion, and reduced the intestinal Npc1L1 to lower cholesterol absorption. Additionally, NACOS enhanced cecum short chain fatty acids production and intestinal integrity. Thus, NACOS supplementation ameliorated atherosclerosis via altering lipid metabolism and reducing inflammation. These findings indicate that NACOS may be a potential functional food material for attenuating atherosclerosis development.展开更多
目的探讨高热量饮食和年龄对载脂蛋白E基因敲除(ApoE^(-/-))小鼠脑功能的影响。方法选取8月龄成年ApoE^(-/-)小鼠和18月龄老年ApoE^(-/-)小鼠共20只,随机分为正常饮食成年组、正常饮食老年组、高热量饮食成年组、高热量饮食老年组,每组...目的探讨高热量饮食和年龄对载脂蛋白E基因敲除(ApoE^(-/-))小鼠脑功能的影响。方法选取8月龄成年ApoE^(-/-)小鼠和18月龄老年ApoE^(-/-)小鼠共20只,随机分为正常饮食成年组、正常饮食老年组、高热量饮食成年组、高热量饮食老年组,每组5只。正常饮食成年组、正常饮食老年组小鼠喂食实验室标准饲料,高热量饮食成年组、高热量饮食老年组小鼠喂食高脂饲料,干预8周。用体质量监测和葡萄糖耐量实验测试小鼠体质量、血糖变化,核磁共振波谱检测海马和下丘脑N-乙酰天冬氨酸(NAA)、胆碱(Cho)含量,Y迷宫和旷场实验检测认知功能,Western blot检测脑组织突触体相关蛋白25(SNAP-25)、突触素(synaptophysin)、突触后致密蛋白95(PSD-95)、诱导型一氧化氮合酶(iNOS)、白细胞介素1β(IL-1β)表达。结果与正常饮食成年组比较,高热量饮食成年组海马NAA、下丘脑Cho和NAA、自发交替率、SNAP-25、synaptophysin、PSD-95表达降低,差异有统计学意义(P<0.05,P<0.01),iNOS、IL-1β表达升高,差异有统计学意义(P<0.01);与正常饮食成年组比较,正常饮食老年组海马NAA、下丘脑Cho、SNAP-25、synaptophysin、PSD-95表达降低(P<0.05,P<0.01),iNOS、IL-1β表达升高(P<0.01);与正常饮食老年组比较,高热量饮食老年组海马和下丘脑Cho和NAA、中心路程/总路程、SNAP-25、synaptophysin、PSD-95表达降低(P<0.05,P<0.01),iNOS、IL-1β表达升高(P<0.01);与高热量饮食成年组比较,高热量饮食老年组海马NAA、中心路程/总路程、平均速度、synaptophysin表达降低(P<0.05,P<0.01),iNOS、IL-1β表达升高(1.61±0.10 vs 1.35±0.13,2.04±0.08 vs 1.54±0.11,P<0.05,P<0.01)。结论高热量饮食导致ApoE^(-/-)小鼠代谢障碍和神经炎症,抑制突触蛋白表达引起认知功能障碍;长期高热量饮食和年龄增加促进ApoE^(-/-)小鼠脑功能衰退。展开更多
文摘目的探讨氧化苦参碱对高脂诱导胰岛素抵抗Apo E^(-/-)小鼠肝脂代谢相关基因的影响。方法 17只♂C57BL/6J小鼠作为对照组,给予正常饮食;68只♂Apo E^(-/-)小鼠,给予高脂饮食,饲养16周后,将小鼠分为模型组、氧化苦参碱低、中、高剂量组。给药8周,测定小鼠体重和一般生化指标。荧光定量PCR和Western blot方法检测肝组织LPL、FAT/CD36、CPT1、UCP2、SREBP-1c、FAS、ACC m RNA和蛋白表达水平。结果氧化苦参碱能不同程度的降低体重、FBG、TC、TG、FFA、FINS、HOMA-IR,升高GIR,改善胰岛素的抵抗。同时降低了LPL、FAT/CD36、UCP2、SREBP-1c、FAS、ACC m RNA和蛋白的表达水平,升高了CPT1表达水平。结论氧化苦参碱能够通过脂转运、氧化、合成3个环节较全面的调节肝脂质代谢,改善高脂诱导的Apo E^(-/-)小鼠的胰岛素抵抗。
基金financially supported by the National Science Found for Excellent Young Scholars (No. 31822037)National Natural Science Foundation of China (No. 21576283)。
文摘Atherosclerosis is driven both by hyperlipidemia and inflammation. Chitin oligosaccharides(NACOS) have shown pharmacological effects on multiple diseases via hypolipidemic and/or anti-inflammatory activities. The present study aims to evaluate whether NACOS treatment can prevent atherosclerosis induced by a highfat-diet(HFD) in Apolipoprotein E-knockout(Apo E;) mice. Results showed that 300 and 900 mg/kg b.w./day NACOS supplementation for 14 weeks significantly decreased atherosclerotic lesions up to 45% and 67% in compared with the HFD(P < 0.05), as measured in the valve area of the aortic root. Further, NACOS supplementation significantly reduced the serum hyperlipidemia and circulating proinflammatory cytokines including interleukin-1β, interleukin-6, monocyte chemoattractant protein-1 and tumor necrosis factor-α. NACOS decreased the hepatic Hmgcr to reduce cholesterol synthesis, activated the genes involved in reverse cholesterol transport to enhance cholesterol efflux and excretion, and reduced the intestinal Npc1L1 to lower cholesterol absorption. Additionally, NACOS enhanced cecum short chain fatty acids production and intestinal integrity. Thus, NACOS supplementation ameliorated atherosclerosis via altering lipid metabolism and reducing inflammation. These findings indicate that NACOS may be a potential functional food material for attenuating atherosclerosis development.
文摘目的探讨高热量饮食和年龄对载脂蛋白E基因敲除(ApoE^(-/-))小鼠脑功能的影响。方法选取8月龄成年ApoE^(-/-)小鼠和18月龄老年ApoE^(-/-)小鼠共20只,随机分为正常饮食成年组、正常饮食老年组、高热量饮食成年组、高热量饮食老年组,每组5只。正常饮食成年组、正常饮食老年组小鼠喂食实验室标准饲料,高热量饮食成年组、高热量饮食老年组小鼠喂食高脂饲料,干预8周。用体质量监测和葡萄糖耐量实验测试小鼠体质量、血糖变化,核磁共振波谱检测海马和下丘脑N-乙酰天冬氨酸(NAA)、胆碱(Cho)含量,Y迷宫和旷场实验检测认知功能,Western blot检测脑组织突触体相关蛋白25(SNAP-25)、突触素(synaptophysin)、突触后致密蛋白95(PSD-95)、诱导型一氧化氮合酶(iNOS)、白细胞介素1β(IL-1β)表达。结果与正常饮食成年组比较,高热量饮食成年组海马NAA、下丘脑Cho和NAA、自发交替率、SNAP-25、synaptophysin、PSD-95表达降低,差异有统计学意义(P<0.05,P<0.01),iNOS、IL-1β表达升高,差异有统计学意义(P<0.01);与正常饮食成年组比较,正常饮食老年组海马NAA、下丘脑Cho、SNAP-25、synaptophysin、PSD-95表达降低(P<0.05,P<0.01),iNOS、IL-1β表达升高(P<0.01);与正常饮食老年组比较,高热量饮食老年组海马和下丘脑Cho和NAA、中心路程/总路程、SNAP-25、synaptophysin、PSD-95表达降低(P<0.05,P<0.01),iNOS、IL-1β表达升高(P<0.01);与高热量饮食成年组比较,高热量饮食老年组海马NAA、中心路程/总路程、平均速度、synaptophysin表达降低(P<0.05,P<0.01),iNOS、IL-1β表达升高(1.61±0.10 vs 1.35±0.13,2.04±0.08 vs 1.54±0.11,P<0.05,P<0.01)。结论高热量饮食导致ApoE^(-/-)小鼠代谢障碍和神经炎症,抑制突触蛋白表达引起认知功能障碍;长期高热量饮食和年龄增加促进ApoE^(-/-)小鼠脑功能衰退。
