Wheat-derived arabinoxylan oligosaccharides with prebiotic effect increase satietogenic gut peptides and reduce metabolic endotoxemia in diet-induced obese mice

Background:

Alterations in the composition of gut microbiota —known as dysbiosis— have been proposed to contribute to the development of obesity, thereby supporting the potential interest of nutrients acting on the gut microbes to produce beneficial effect on host energetic metabolism. Non-digestible fermentable carbohydrates present in cereals may be interesting nutrients able to influence the gut microbiota composition.

Objective and design:

The aim of the present study was to test the prebiotic potency of arabinoxylan oligosaccharides (AXOS) prepared from wheat bran in a nutritional model of obesity, associated with a low-grade chronic systemic inflammation. Mice were fed either a control diet or a high fat (HF) diet, or a HF diet supplemented with AXOS during 8 weeks.

Results:

AXOS supplementation induced caecal and colon enlargement associated with an important bifidogenic effect. It increased the level of circulating satietogenic peptides produced by the colon (peptide YY and glucagon-like peptide-1), and coherently counteracted HF-induced body weight gain and fat mass development. HF-induced hyperinsulinemia and the Homeostasis Model Assessment of insulin resistance were decreased upon AXOS feeding. In addition, AXOS reduced HF-induced metabolic endotoxemia, macrophage infiltration (mRNA of F4/80) in the adipose tissue and interleukin 6 (IL6) in the plasma. The tight junction proteins (zonula occludens 1 and claudin 3) altered upon HF feeding were upregulated by AXOS treatment suggesting that the lower inflammatory tone was associated with the improvement of gut barrier function.

Conclusion:

Together, these findings suggest that specific non-digestible carbohydrates produced from cereals such as AXOS constitute a promising prebiotic nutrient in the control of obesity and related metabolic disorders.     

温阳解毒化瘀颗粒对肠源性内毒素血症大鼠肠黏膜上皮紧密连接的影响

目的：研究温阳解毒化瘀颗粒对肠源性内毒素血症（ IETM ）模型大鼠结肠黏膜上皮紧密连接的影响,探索其抗肝衰竭的作用机制。方法：将大鼠随机分为正常组、模型组、温阳解毒化瘀颗粒（实验组）和对照组4组,采用D-半乳糖胺（D-gal）腹腔注射致肝衰竭ITEM大鼠模型。正常组在腹腔注射生理盐水24h后处死,模型组、实验组、对照组分别于造模后24h、48h、72h各取6只、7只、7只大鼠处死,检测各组肝功能、内毒素、结肠黏膜上皮咬合蛋白（occludin）及肌球蛋白轻链激酶（MLCK）。结果：模型组血清ALT/AST、内毒素、 MLCK表达水平均高于正常组, occludin表达低于模型组（ P＜0.01）;实验组血清ALT/AST、内毒素、 MLCK表达水平均低于模型组, occlu-din表达高于模型组（ P＜0.05）。结论：增强结肠粘膜上皮紧密连接功能,降低内毒素的吸收是温阳解毒化瘀颗粒抗肝衰竭的作用机制之一。     

阳明病(阳明腑实证)模型大鼠“欲解时”相关炎症因子变化的研究

目的:通过观察阳明病(阳明腑实证)模型大鼠"欲解时"血常规及肠黏膜上有关炎症因子的变化,初步探讨阳明病"欲解时"的病理生理学基础。方法:实验大鼠随机分为欲解时对照组、欲解时模型组、非欲解时对照组、非欲解时模型组,建立阳明腑实证大鼠模型后,分别于阳明病"欲解时"及"非欲解时"每天取血及肠组织,连续5d,血细胞分析仪检测血常规,免疫组化法测Toll样受体4(TLR4)蛋白含量,荧光实时定量聚合酶链反应(PCR)检测肠组织TLR4 mRNA水平。结果:欲解时模型组大鼠白细胞、中性粒细胞、单核细胞数较非欲解时模型组升高,其中单核细胞数上升差异有统计学意义(P<0.05);模型组淋巴细胞显著低于对照组(P<0.05)。欲解时模型组TLR4 mRNA及蛋白较非欲解时模型组显著降低,第1天TLR4 mRNA相对表达量差异有统计学意义(P<0.05)。结论:阳明腑实证病程中,欲解时模型组大鼠中性粒及淋巴细胞较对照组体现出较早较长时间的差异性,意味着欲解时的免疫反应更为明显。通过TLR4检测表明欲解时阳明腑实证的炎症反应较非欲解时轻,可能与其表达下调相关炎性介质的释放减少有关。     

Suppression of hemopoiesis during CCl4-induced hepatic fibrosis: Role of systemic endotoxemia

CCl₄-induced hepatic fibrosis in mice was accompanied by insufficiency of bone marrow myelo- and erythropoiesis. Polymyxin B completely abolished these changes. This phenomenon can be explained by the development of macrophage endotoxin tolerance during hepatic fibrosis. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 130, No. 8, pp. 172–175, August, 2000     

Impact of dietary fat on gut microbiota and low-grade systemic inflammation: mechanisms and clinical implications on obesity

Dietary fat strongly affects human health by modulating gut microbiota composition and low-grade systemic inflammation. High-fat diets have been implicated in reduced gut microbiota richness, increased Firmicutes to Bacteroidetes ratio, and several changes at family, genus and species levels. Saturated (SFA), monounsaturated (MUFA), polyunsaturated (PUFA) and conjugated linolenic fatty acids share important pathways of immune system activation/inhibition with gut microbes, modulating obesogenic and proinflammatory profiles. Mechanisms that link dietary fat, gut microbiota and obesity are mediated by increased intestinal permeability, systemic endotoxemia, and the activity of the endocannabinoid system. Although the probiotic therapy could be a complementary strategy to improve gut microbiota composition, it did not show permanent effects to treat fat-induced dysbiosis. Based upon evidence to date, we believe that high-fat diets and SFA consumption should be avoided, and MUFA and omega-3 PUFA intake should be encouraged in order to regulate gut microbiota and inflammation, promoting body weight/fat control.     

内毒素致家兔急性肺损伤时肺和肺外脏器的病理组织学变化及东莨菪碱和前列腺素E_1的保护作用

目的：了解内毒素血症时各脏器受损的病理组织学变化及东莨菪碱和前列腺素Ｅ１的保护作用。方法：大耳白兔５０只，随机分为５组：Ａ组为对照组；Ｂ组为内毒素致伤组（７００μｇ／ｋｇ）；Ｃ组、Ｄ组分别为内毒素致伤后东莨菪碱和前列腺素Ｅ１治疗组，Ｅ组为东莨菪碱和前列腺素Ｅ１联合治疗组。实验前及实验后０．５、２、４和６小时分别测血压和呼吸频率；实验后６．５小时放血处死动物，测肺毛细血管通透指数，同时取肺、心、脑、肝、肾、肾上腺和脾组织作光镜及电镜检查。结果：Ｂ组动物全部于实验后０．５小时出现休克和呼吸困难；６．５小时测得的肺毛细血管通透指数显著高于对照组，各脏器的病理组织学改变以肺最为明显且严重。各治疗组肺受损均轻于Ｂ组，其它脏器在实验后６．５小时的病理变化不明显。结论：内毒素休克时，肺是敏感且最早受损的脏器；东莨菪碱和前列腺素Ｅ１联合治疗组的疗效基本与两药单独治疗组相同。     

祛毒冲剂治疗肠源性内毒素血症的临床研究

目的:观察祛毒冲剂对危重病肠源性内毒素血症的治疗价值.方法:61例肠源性内毒素血症患者随机分为祛毒冲剂组(30例)和思密达组(31例),在治疗前,治疗后1、3和7 d分别观测、记录患者一般体征变化,清晨空腹采外周静脉血测定白细胞计数、血浆内毒素及血清肿瘤坏死因子(TNF)水平.结果:祛毒冲剂组外周血白细胞计数下降速度明显快于思密达组,3 d后差异有显著性(P<0.01),排便次数多于思密达组(P=0.000),并可较快地降低血浆内毒素及血清TNF水平(P均<0.01).结论:祛毒冲剂可以有效地降低血浆内毒素及血清TNF水平,并改善患者的临床症状,促进患者康复.     

创伤早期内毒素血症

目的：探讨严重创伤患者早期内毒素血症参与早期全身炎症反应的可能性和其变化趋势对评估预后的意义。方法：监测２５例严重创伤患者伤后２４小时～２８日的内毒素水平和血液细菌学培养，１０例患者行血流动力学监测（７２小时）；２２例健康成人血标本的内毒素值作对照。结果：全组患者可以早至伤后２４小时内即发生内毒素血症〔（３６１±６０１）ＥＵ／Ｌ（ＥＵ为内毒素单位）〕，与正常健康人〔对照组血内毒素（７４±２３）ＥＵ／Ｌ〕比较，Ｐ＜０．０５；１０例行血流动力学监测者表现典型的高动力型循环和高代谢状态；存活组内毒素呈下降趋势，至伤后７日〔（１２５±１９８）ＥＵ／Ｌ〕与对照组差异不显著；死亡组与ＭＯＤＳ组内毒素持续不降或继续升高。结论：严重创伤后２４小时内即可形成内毒素血症，推测系来源于胃肠道粘膜屏障损伤所致的毒素易位。这种早期内毒素血症可能参与伤后早期全身炎症反应；测定内毒素水平变化对评估患者预后有重要意义     

甘氨酸对高果糖饮食诱导的大鼠胰岛素抵抗及认知功能损害的影响

目的: 探讨肠源性内毒素血症(IETM)在长期高果糖饮食诱导的大鼠胰岛素抵抗(IR)及认知功能损害中的作用,及甘氨酸对其的保护机制。方法: 模型组大鼠以8%果糖水喂养,干预组给予8%果糖+1%甘氨酸水喂养。每月检测体重及收缩压。8个月后,检测血糖、血脂、糖耐量及血浆内毒素(LPS)变化;ELISA法检测血浆胰岛素、血浆及皮层促炎因子水平;计算胰岛素抵抗指数(HOMA-IR);Western blotting测定皮层胰岛素受体信号转导蛋白的表达;应用Morris水迷宫测试大鼠认知功能。结果: 模型组在第3月~第6月体重增长明显,第3月后收缩压明显升高;甘氨酸在第4月和第6月显著降低模型组体重增长,第4~第6月降低收缩压的升高。甘氨酸部分改善模型组血脂和糖耐量异常,降低血浆LPS、血浆胰岛素、HOMA-IR、血浆和皮层促炎因子水平。此外,甘氨酸还明显改善模型组皮层胰岛素信号转导蛋白的异常表达及认知功能损害。结论: 长期高果糖饮食诱导大鼠发生外周及中枢的IR,同时伴有IETM和轻度炎症;甘氨酸通过减轻IETM改善高果糖饮食诱导的IR和认知功能损害。     

GRP78在肝硬化大鼠肠源性内毒素血症引发心脏病变中的作用

目的: 探讨葡萄糖调节蛋白78(GRP78)在肝硬化大鼠肠源性内毒素血症引发心脏病变中的作用。方法: 51只Wistar雄性大鼠随机分为肝硬化模型4周组、6周组、8周组和同期正常对照组。于第8周检测大鼠心功能;检测各组心肌组织匀浆中肿瘤坏死因子α(TNF-α)和丙二醛(MDA)水平;甲苯胺蓝染色和van Giesan染色分别观察心肌细胞数量的变化和计算心肌胶原容积分数(CVF);免疫组化法检测心肌组织GRP78和缺氧诱导因子1α(HIF-1α)蛋白表达情况。结果: 随肝硬化病程进展:(1)肝硬化8周组大鼠左室舒张末期压(LVEDP)及左室内压最大上升和下降速率(±LV dp/dt_max)均较对照组降低(P<0.05);(2)心肌组织中TNF-α、MDA、CVF、GRP78蛋白和HIF-1α蛋白水平均逐渐升高并显著高于正常对照组(P<0.05);(3)甲苯胺蓝染色显示模型各组心肌细胞数量逐渐减少并显著低于正常对照组(P<0.05);(4)血浆中内毒素水平分别与丙氨酸氨基转移酶(ALT)、同型半胱氨酸(Hcy)、TNF-α、GRP78和MDA呈显著正相关(P<0.05);(5)GRP78蛋白分别与HIF-1α、Hcy、MDA、ALT和CVF呈显著正相关(P<0.05)。结论: 肝硬化大鼠伴发的肠源性内毒素血症通过直接或间接作用引起内质网应激和GRP78表达增加,后者可能是引起心肌重构、导致心脏功能变化的关键分子。