基于肠-肝轴探讨安化黑茶防治非酒精性脂肪肝的作用机制

为探讨安化黑茶水提液预防小鼠非酒精性脂肪肝（non-alcoholic fatty liver disease,NAFLD）的作用机制。将C57BL/6J小鼠随机分为空白组、模型组、西药（阿托伐他汀,10 mg/kg）组及安化黑茶低、中、高剂量（0.75、1.5、3.0 g/kg）组,采取预防模型,同时给药与饲喂高脂高糖饲料,连续10周。结果表明：与模型组小鼠相比,安化黑茶低、中、高剂量组小鼠体质量极显著降低（P<0.01）,体质量增长量极显著减少（P<0.01）,胆固醇（total cholesterol,TC）、甘油三酯（triglycerides,TG）、低密度脂蛋白（low-density lipoprotein cholesterol,LDL-C）、丙氨酸氨基转移酶（alanine aminotransferase,ALT）水平明显降低（P<0.05,P<0.01）,肝细胞脂肪变性与气球样变得到纠正,回肠病理损伤改善,闭合蛋白和闭锁小带蛋白-1(zonula occludens-1,ZO-1)表达增加（P<0.01）;安化黑茶高剂量组拟杆菌门、Muribaculaceae＿unclassified及乳杆菌属相对丰度增加,厚壁菌门、脱硫弧菌属及毛螺菌属相对丰度降低。综上所述,安化黑茶具有改善肠黏膜屏障功能,调节肠道菌群,恢复肠道微生态的作用,其可能通过调节肠-肝轴发挥对NAFLD的防治作用。     

The target cells of anthocyanins in metabolic syndrome

Abstract

Metabolic syndrome develops to several related chronic diseases, such as obesity, cardiovascular disease, hypertension, diabetes, and fatty liver disease. Diseases are outcomes of various cells dysfunction, which are especially acting with a network in metabolic syndrome. Anthocyanins are natural edible pigments widely existed in dark-colored fruits, vegetables, and grains. Epidemiological investigation and nutritional intervention of anthocyanins have exhibited broad-spectrum biological effects that they can benefit patients with metabolic syndrome related chronic diseases. Whereas the underlying mechanisms and the effects of anthocyanins on critical cells in chronic metabolic diseases are complex and elusive. Therefore, this review summarizes the studies about the effects of anthocyanins on various metabolism related chronic diseases, and mainly focuses on the effects and underlying molecular mechanisms on critical cells. We confirmed that anthocyanins are efficient on adipocytes, endothelial cells, inflammatory cells, hepatocytes, intestinal cells and gut microbiota, but lack of evidence on platelets, skeletal muscle cells, hepatic stellate cells and pancreatic beta cells. Additionally, we discussed the structure-function relationship of anthocyanins and the metabolites. This review summarizes the development of studies on anthocyanins with its target cells in metabolic syndrome, and discusses the unclear aspects of the anthocyanins research work, which is necessary for the future clinical application.     

二十碳五烯酸酰化虾青素改善小鼠溃疡性结肠炎的机制

目的:探究二十碳五烯酸酰化虾青素(EPA-AST)对葡聚糖硫酸钠(DSS)诱导溃疡性结肠炎(UC)的保护作用。方法:建立3%DSS诱导的结肠炎模型,雄性C57BL/6小鼠随机被分为4组(n=8):对照组、DSS组、虾青素组(AST)和EPA-AST组。通过评估小鼠疾病活动指数、结肠长度等指标分析受试物在改善UC症状方面的差异,分析受试物对小鼠病灶组织的氧化应激、细胞凋亡、炎症因子、肠道屏障等方面的影响,探究其潜在的作用机制。收集小鼠结肠内粪便,采用高通量测序技术分析肠道菌群丰度、结构等微环境的稳态指标。结果:与模型组相比,AST和EPA-AST的疾病活动指数和体质量明显降低(P<0.05),结肠长度由5 cm增加至7 cm。EPA-AST通过激活NLRP3/ASC信号通路,降低髓过氧化物酶(MPO)活性(3.85 U/mg prot),减少肠道屏障凋亡,增加紧密连接蛋白(Occludin和ZO-1)表达来调节炎症反应(P<0.05)。此外,AST和EPA-AST还提高了α-多样性,并上调有益菌(拟杆菌门和疣微菌门)的丰度,同时下调有害菌(厚壁菌门和变形菌门)的丰度。结论:EPA-AST在缓解结肠炎方面的表现优于AST,EPA-AST通过多靶点形式改善了炎症性肠病。     

肠道菌群对膳食麸质所致乳糜泻的影响

乳糜泻是由遗传易感人群因摄入膳食麸质而诱发的一种自身免疫性肠病。麸质是一类日常膳食中广泛存在的蛋白复合物,其不易被消化道完全吸收,从而激活遗传易感个体肠道内异常的固有免疫和适应性免疫反应。最新研究支持肠道菌群紊乱是乳糜泻发生与发展的关键因素之一。本文分别综述乳糜泻发病诱因、病理和治疗策略3个方面,旨在揭示肠道菌群在乳糜泻病理中的作用,并为临床上乳糜泻的防治提供理论参考。     

低聚半乳糖对便秘小鼠的缓解作用及机制

目的：研究低聚半乳糖（galacto-oligosaccharides,GOS）对洛派丁胺（loperamide,Lop）诱导的小鼠便秘的缓解作用及其机制,为便秘治疗提供新依据。方法：将36只雄性BALB/C小鼠随机分为3组,分别为空白组、造模组、GOS组。检测各组小鼠生长状态、排便情况和小肠推进率。利用HE染色观察结肠组织形态变化;实时荧光定量聚合酶链式反应测定小鼠结肠中水通道蛋白、粘蛋白和紧密连接蛋白的mRNA表达;16S rRNA测序分析粪便肠道菌群;气相色谱法测定短链脂肪酸含量。结果：与造模组相比,GOS组小鼠体重增加量显著提高（P<0.05）,首颗黑便排出时间显著缩短（P<0.05）,5 h粪便颗粒数和含水量显著增加（P<0.05）;结肠组织损伤缓解;结肠组织中AQP4和AQP8的mRNA表达降低69.30%和56.38%,Muc2、Muc3和Zo-1的mRNA表达提高74.94%、61.61%和73.49%,均出现显著差异（P<0.05）;粪便中有益菌Lactobacillus和norank_f_Muribaculaceae的丰度增加,丙酸和丁酸含量显著增加（P<0.05）。结论：GOS具有显著的缓解便秘作用,其机制可能与修复肠道屏障损伤、调节肠道水代谢和肠道菌群组成有关。     

益生菌和粪菌移植调节炎症性肠病的研究进展

炎症性肠病（inflammatory bowel diseases,IBD）是一种易复发的慢性胃肠道炎症性疾病,近年来在世界范围内的发病率逐渐上升。IBD的发病因素复杂,主要是由遗传、环境、免疫等因素相互作用导致的,随着宿主-肠道微生物相互作用的深入研究,人们发现肠道菌群在IBD的进展中发挥着重要作用,因此基于调节肠道微生物群缓解或治疗IBD的新型方法也备受关注。近年来的大量研究都表明益生菌、粪菌移植可以通过调节肠道微生物的组成、增强肠道屏障功能、调节机体免疫反应等达到缓解IBD的目的。因此,本文对IBD的发病因素以及益生菌、粪菌移植调节IBD的研究进展进行综述。     

刺梨多糖对非酒精性脂肪肝小鼠回肠黏膜屏障功能的影响

为研究刺梨多糖（Rosa roxburghii Tratt polysaccharides,RTFP）对非酒精性脂肪肝（non-alcoholic fatty liver disease,NAFLD）诱导的小鼠回肠肠道黏膜屏障功能障碍和肠道炎症的改善作用,以及刺梨多糖对肠道菌群的影响,本研究采用高脂肪饮食（high fat diet,HFD）喂养小鼠,构建NAFLD小鼠模型,然后灌胃RTFP,干预7周。结果表明,RTFP可显著降低NAFLD诱导的小鼠回肠炎症因子和氧化应激水平,改善脂质代谢紊乱状况。微观组织病理学观察发现,RTFP可以使小鼠回肠结构形态趋向于正常水平,减少隐窝病变,保护肠道屏障。通过16S rRNA高通量测序评估各处理组小鼠粪便微生物群的变化,发现RTFP可调节NAFLD小鼠肠道菌群的多样性和组成,厚壁菌门（Firmicutes）与拟杆菌门（Bacteroidetes）比值明显降低,提高了有益菌群的相对丰度,降低了病原菌群的相对丰度。RTFP可以作为一种益生元调节肠道菌群,改善NAFLD模型小鼠的肠道微生态,减轻肠道屏障功能障碍,维持肠道正常功能。     

Beneficial effects of Lactobacillus rhamnosus hsryfm 1301 fermented milk on rats with nonalcoholic fatty liver disease

A growing stream of research suggests that probiotic fermented milk has a good effect on nonalcoholic fatty liver disease. This work aimed to study the beneficial effects of Lactobacillus rhamnosus hsryfm 1301 fermented milk (fermented milk) on rats with nonalcoholic fatty liver disease induced by a high-fat diet. The results showed that the body weight and the serum levels of total cholesterol, total glyceride, low-density lipoprotein, alanine transaminase, aspartate aminotransferase, free fatty acid, and reactive oxygen species were significantly increased in rats fed a high-fat diet (M) for 8 wk, whereas high-density lipoprotein cholesterol and superoxide dismutase were significantly decreased. However, the body weight and the serum levels of total cholesterol, total glyceride, alanine transaminase, aspartate aminotransferase, free fatty acid, reactive oxygen species, interleukin-8, tumor necrosis factor-α, and interleukin-6 were significantly decreased with fermented milk (T) for 8 wk, and the number of fat vacuoles in hepatocytes was lower than that in the M group. There were significant differences in 19 metabolites in serum between the M group and the C group (administration of nonfermented milk) and in 17 metabolites between the T group and the M group. The contents of 7 different metabolites, glycine, glycerophosphocholine, 1,2-dioleoyl-sn-glycero-3-phosphocholine, thioetheramide-PC, d-aspartic acid, oleic acid, and l-glutamate, were significantly increased in the M group rat serum, and l-palmitoyl carnitine, N6-methyl-l-lysine, thymine, and 2-oxadipic acid were significantly decreased. In the T group rat serum, the contents of 8 different metabolites—1-O-(cis-9-octadecenyl)-2-O-acetyl-sn-glycero-3-phosphocholine, acetylcarnitine, glycine, glycerophosphocholine, 1,2-dioleoyl-sn-glycero-3-phosphocholine, d-aspartic acid, oleic acid, and l-glutamate were significantly decreased, whereas creatinine and thymine were significantly increased. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that 50 metabolic pathways were enriched in the M/C group and T/M group rat serum, of which 12 metabolic pathways were significantly different, mainly distributed in lipid metabolism, amino acid, and endocrine system metabolic pathways. Fermented milk ameliorated inflammation, oxygenation, and hepatocyte injury by regulating lipid metabolism, amino acid metabolic pathways, and related metabolites in the serum of rats with nonalcoholic fatty liver disease.     

膳食油脂与非酒精性脂肪肝病形成相关研究进展

市场中的膳食油脂产品琳琅满目,消费者在选择食用油的过程中通常会考虑其对健康的影响,尤其是广泛流行的营养代谢性疾病非酒精性脂肪肝病（NAFLD）。我国NAFLD的患病率持续增长,给个人和社会造成巨大的压力。大量的研究表明,膳食油脂与NAFLD的形成关系密切,合理的膳食用油能有效预防NAFLD。通过对油脂脂肪酸链长、饱和度及双键位置、奇偶性与NAFLD形成的相关研究进行梳理,结合饮食模式综述了膳食油脂与NAFLD形成相关研究进展,以期为学术探索和日常膳食油脂提供依据。