Short communication: Pheromonicin-SA affects mRNA expression of toll-like receptors, cytokines, and lactoferrin by Staphylococcus aureus-infected bovine mammary epithelial cells

Pheromonicin-SA (Ph-SA) is a newly developed, engineered multidomain peptide that has a bactericidal effect against Staphylococcus aureus. The objective of this study was to characterize innate immune responses by Staph. aureus-stimulated bovine mammary epithelial cells (BMEC) following treatment with Ph-SA. Primary BMEC from one lactating Holstein cow were isolated and exposed to Staph. aureus for 2 h, and then treated with rifampicin or Ph-SA. Total RNA was isolated from BMEC at 0, 2, 6, 12, and 24 h postinfection, and the mRNA expression of selected genes, including toll-like receptor (TLR)2 and TLR4, IL-1β, IL-6, IL-8, tumor necrosis factor α (TNF-α), and lactoferrin, was quantified by real-time PCR. In the rifampicin group, increases in the expression of mRNA for TNF-α, IL-1β, IL-6, IL-8, and lactoferrin were observed at 6 h postinfection and in the expression of mRNA for TLR2 but not for TLR4 at 12 h postinfection. In the Ph-SA group, increases in the mRNA expression of TLR2, TNF-α, IL-1β, IL-6, IL-8, and lactoferrin were observed at 6 h postinfection, and an increase in TLR4 mRNA expression was observed at 24 h postinfection. At 24 h postinfection, the mRNA expression of TLR4, TNF-α, IL-1β, IL-6, IL-8, and lactoferrin was higher in the Ph-SA group than in the rifampicin group. In conclusion, Ph-SA might promote the expression of mRNA for TLR2, TLR4, the pro-in?ammatory cytokines IL-1, IL-6, and TNF-α, the chemotactic factor IL-8, and lactoferrin in Staph. aureus-infected BMEC. Moreover, Ph-SA may be of value as an antibiotic in promoting innate immune responses by Staph. aureus-infected bovine mammary epithelial cells.     

Immunomodulatory effect of Ganoderma atrum polysaccharide on CT26 tumor-bearing mice

Ganoderma atrum has attracted great attention for its antitumor activity. However, the mechanism remains unclear. A G. atrum polysaccharide (PSG-1) showed pronounced antitumor activity in this study. PSG-1 did not kill CT26 cells directly, but inhibited the proliferation of CT26 cells via the activation of peritoneal macrophages (MΦ). In vivo, PSG-1 significantly suppressed the tumor growth in CT26 tumor-bearing mice. The treatment caused a significant increase in the immune organ index and the phagocytosis of macrophages. The production of TNF-α, IL-1β and nitric oxide also increased. Furthermore, we found that PSG-1 acted on Toll-like receptor (TLR) 4, signaled through p38 MAPK pathway, then activated NF-κB and stimulated TNF-α production. We further found that PSG-1 increased the expression of TLR4 and NF-κB, the degradation of IκBα and the phosphorylation of p38 MAPK. In summary, we have demonstrated that PSG-1 could activate macrophages via TLR4-dependent signaling pathways, improve immunity and inhibit tumor growth.     

红毛藻多糖对环磷酰胺诱导的免疫抑制小鼠的免疫调节机理

本研究以环磷酰胺（cyclophosphamide,CTX）诱导的免疫力低下小鼠为模型,探究红毛藻多糖（Bangia fusco-purpurea polysaccharides,BFP）对免疫抑制小鼠免疫力的影响。结果表明,BFP干预能够显著提高免疫抑制小鼠自然杀伤细胞活性、巨噬细胞吞噬能力和清除碳颗粒能力;增强T淋巴细胞增殖作用,上调CD4＋ T细胞比例,降低CD8＋ T细胞比例并增加CD4＋/CD8＋,降低辅助性T细胞17和CD3－CD19＋ B细胞的比例;提高血清溶血素、免疫球蛋白（immunoglobulin,Ig）A和IgG、免疫相关细胞因子白细胞介素（interleukin,IL）-2、IL-6、肿瘤坏死因子-α（tumor necrosis factor-α,TNF-α）、干扰素-γ（interferon-γ,INF-γ）的质量浓度,对免疫抑制小鼠的非特异性免疫、细胞免疫及体液免疫均具有良好的调节作用。在明确BFP对免疫抑制小鼠免疫功能具有保护作用的基础上,分析其对免疫抑制小鼠肠道相关免疫细胞表面受体的影响,发现BFP能够显著或极显著下调Toll样受体（Toll-like receptor,TLR）2、TLR4、IL-6和TNF-α基因（P＜0.05）和蛋白（P＜0.01）的表达,推测BFP通过TLR2/TLR4下游相关信号通路调节轴发挥增强免疫力的功能。本研究可为深入认识海洋食品的营养价值,推进海洋食品在居民膳食中的应用提供科学依据。     

动物双歧杆菌乳亚种XLTG11对克林霉素诱导的抗生素相关性腹泻的改善作用

目的：通过克林霉素诱导抗生素相关性腹泻(antibiotic-associated diarrhea,AAD)模型,探究动物双歧杆菌乳亚种XLTG11缓解小鼠AAD的作用。方法：将48只6周龄C57BL/6N雄鼠随机分为4组：对照组、模型组、低剂量组和高剂量组,除对照组外,各组小鼠连续14 d灌胃克林霉素(250 mg/(kg m_b·d))诱导AAD模型,然后低剂量组和高剂量组灌胃不同剂量(0.2 mL,5×10⁶、1×10⁷ CFU)动物双歧杆菌乳亚种XLTG11,测定小鼠体质量增长量、盲肠质量、粪便含水量和粪便稠度,测定结肠肿瘤坏死因子α、白细胞介素6(interleukin 6,IL-6)、IL-1β、IL-10水平,血清脂多糖(lipopolysaccharide,LPS)和D-乳酸质量浓度,测定肠道菌群组成及短链脂肪酸含量,以及肠道屏障和核因子κB(nuclear factor kappa-B,NF-κB)信号通路相关基因表达水平。结果：高剂量动物双歧杆菌乳亚种XLTG11显著提高AAD模型小鼠的体质量增长量和...     

黑灵芝多糖体内抗炎活性及对甘露糖受体表达的影响

目的:研究水溶性黑灵芝多糖(a water-soluble polysaccharides from Ganoderma atrum,PSG)-1体内抗炎活性及对甘露糖受体(mannose receptor,MR)表达的影响。方法:腹腔注射脂多糖(lipopolysaccharide,LPS)建立小鼠体内炎症模型,随机分为5组:正常对照组、LPS组、PSG-1(高、中、低剂量,分别为100、50、25 mg/(kg·d))+LPS组。流式细胞仪检测巨噬细胞中MR表达、吞噬功能及活性氧(reactive oxygen species,ROS)生成,用酶联免疫吸附测定(enzyme-linked immunosorbent assay,ELISA)分析血清中肿瘤坏死因子(tumor necrosis factor,TNF)-α、白细胞介素(interleukin,IL)-1β和IL-6的含量。结果:与正常对照组相比,LPS组腹腔巨噬细胞表面MR表达量下降,与LPS组相比,PSG-1+LPS组腹腔巨噬细胞表面MR表达量极显著增加(P0.01);与正常对照组相比,LPS组腹腔巨噬细胞吞噬能力和ROS生成增加,与LPS组相比,PSG-1+LPS组腹腔巨噬细胞吞噬功能和ROS生成显著降低(P0.05,P0.0 1);与正常对照组相比,小鼠经LPS处理后,血清中TNF-α、IL-1β和I L-6的分泌水平极显著升高(P0.01);与LPS组相比,小鼠灌胃PSG-1后,PSG-1(高剂量)+LPS组中TNF-α的含量显著降低(P0.05),IL-1β和IL-6的分泌水平无显著差异。结论:PSG-1具有抗炎作用,可部分抑制LPS诱导的体内炎症,其机理与PSG-1促进小鼠腹腔巨噬细胞表面MR的表达、抑制巨噬细胞向M1型极化有关。     

人参、甘草、五味子复合醋提物对老年小鼠急性炎性肝损伤保护作用的研究

目的:本研究旨在通过脂多糖（Lipopolysaccharide,LPS）诱导肝损伤小鼠考察复合醋提物（MVE）对老年小鼠炎性肝损伤的保护效果。方法:将小鼠随机分为正常对照组、MVE组、LPS组、LPS+MVE组。通过苏木精-伊红染色评估肝组织病理情况和免疫组织化学染色判断髓过氧化物酶的表达变化。同时,检测肝组织中白介素-1β、白介素-17、CXC趋化因子配体1、CXC趋化因子配体17等生化因子水平。免疫印迹法测定肝脏中Toll样受体4（Toll-like receptor 4,TLR4）和p-NF-κB p65蛋白表达量变化。结果:复合醋提物能减少中性粒细胞及炎症细胞浸润,极显著降低LPS模型小鼠肝脏谷丙转氨酶（ALT）、谷草转氨酶（AST）、活性氧（ROS）水平（P<0.01）,并降低促炎因子和中性粒细胞趋化因子水平（P<0.05）,降低炎症通路TLR4和p-NF-κB p65的蛋白表达水平（P<0.001）。结论:MVE能改善LPS诱导急性炎症小鼠的肝损伤,此外,MVE还能通过平衡促炎和抗炎因子水平变化、抑制TLR4-NF-κB信号通路,最终达到发挥护肝作用效果。     

榆干离褶伞溶栓酶对脂多糖诱导的血管内皮细胞损伤的保护作用

目的：探讨榆干离褶伞溶栓酶对脂多糖（lipopolysaccharide,LPS）诱导的血管内皮细胞炎性损伤的保护作用。方法：以LPS诱导人脐静脉内皮细胞（human umbilical vein endothelial cells,HUVEC）炎性损伤。将HUVEC分为空白对照组、模型组和榆干离褶伞溶栓酶（Lyophyllum ulmarium fibrinolytic enzyme,LUFE）低、中、高剂量组。采用噻唑蓝法测定HUVEC存活率,通过酶联免疫吸附测试法检测细胞上清液乳酸脱氢酶（lactate dehydrogenase,LDH）、肿瘤坏死因子α（tumor necrosis factor α,TNF-α）、白介素6（interleukin 6,IL-6）、E-选择素和单核细胞趋化因子1（monocyte chemoattractant protein 1,MCP-1）水平。流式细胞术检测细胞间黏附分子1（intercellular cell adhesion molecule 1,ICAM-1）表达水平,采用Hoechst染色法观察HUVEC与人急性单核细胞白血病细胞系（human acute monocytic leukemia cell line-1,THP-1）的黏附作用。用蛋白印迹实验检测HUVEC的Toll样受体4（toll-like receptor 4,TLR4）、丝裂原活化蛋白激酶（mitogen-activated protein kinase,MAPK）以及核因子-κB（nuclear factor κB,NF-κB）通路中主要蛋白（髓样分化因子88（myeloid differentiation factor 88,MyD88）、转化生长因子β激活激酶1（transforming growth factor β activated kinase 1,TAK1）、磷酸化TAK1（phosphorylated TAK1,p-TAK1））的表达和活化情况。结果：LUFE能够抑制LPS所诱导的HUVEC培养上清液LDH、TNF-α、IL-6、E-选择素和MCP-1水平的升高,降低细胞ICAM-1表达水平并减弱HUVEC与THP-1的黏附作用。与模型组比较,LUFE各剂量组TLR4、MyD88、p-TAK1/TAK1、磷酸化c-Jun氨基末端激酶（phosphorylated c-Jun N-terminal kinase,p-JNK）/JNK、p-p38/p38、p-NF-κB/NF-κB水平显著降低（P＜0.05）。结论：LUFE对血管内皮细胞的炎性损伤具有保护作用,其作用机制可能是通过抑制TLR4/MyD88/TAK1/NF-κB信号通路及MAPK通路,进而降低炎症因子水平,从而保护血管内皮细胞。     

蛹虫草多糖调节小鼠巨噬细胞RAW264.7免疫活性的分子机制

多种真菌多糖近年来因其免疫调节活性成为保健食品领域研究的热点。本实验以食药用真菌蛹虫草提取物蛹虫草多糖（Cordyceps militaris polysaccharides,CMP）为研究材料,初步探究CMP对小鼠巨噬细胞RAW264.7免疫活性的调节机制。噻唑蓝实验结果显示CMP无细胞毒性,且100、200 μg/mL CMP可以明显增强RAW264.7细胞活性;中性红法、Griess法和酶联免疫吸附检测结果表明25～200 μg/mL的CMP以剂量依赖方式增强RAW264.7细胞吞噬活性并增加一氧化氮（nitric oxide,NO）和白介素-1β（interleukin-1β,IL-1β）分泌,肿瘤坏死因子-α（tumor necrosis factor-α,TNF-α）的分泌呈先升高后降低的趋势,在100 μg/mL时达到最高值;抑制剂中和实验结果显示当Toll样受体4（Toll-like receptors 4,TLR4）和甘露糖受体（mannose receptor,MR）受到抑制时,CMP诱导的RAW264.7免疫反应显著降低,这表明TLR4和MR均为CMP激活巨噬细胞的受体;此外,Western blot结果显示丝裂原活化蛋白激酶（mitogen-activated protein kinases,MAPK）信号通路也参与CMP诱导的RAW264.7细胞分泌NO、TNF-α和IL-1β。表明TLR4和MR/MAPK信号传导途径在CMP诱导巨噬细胞RAW264.7产生免疫应答时发挥了重要作用。     

茯苓多糖通过NF-κB和NLRP3信号通路调节脂多糖引起的焦虑和抑郁样行为

目的：探讨茯苓多糖（Poria cocos polysaccharide,PPS）对脂多糖（LPS）引起的焦虑和抑郁样行为的影响,并分析其机制。方法：BV-2细胞分成对照组、LPS组、LPS+氟西汀组、LPS+PPS(PPS分别为4、8、16μmol/L),处理24 h,二氯二氢荧光素二氢乙酸酯（DCFH-DA）荧光探针检测细胞内活性氧（ROS）水平,Griess法检测培养上清液NO水平,酶联免疫吸附试验（ELISA）检测培养上清液中TNF-α、IL-1β水平,Western blot实验检测CD206、CD16/32、NF-κB p65水平。动物实验将小鼠分为对照组、模型组、LPS+氟西汀组、LPS+PPS低剂量组（20 mg/kg）、LPS+PPS高剂量组（80 mg/kg）,每组10只,测试抑郁样行为,检测海马组织TNF-α、IL-1β、IL-18的浓度,分析海马组织CD206、CD16/32、NF-κB p65、NLRP3、ASC、Cleaved caspase-1蛋白水平。结果：与LPS组比较,4、8、16μmol/L PPS能极显著降低ROS荧光相对强度（P<0.01...     

The use of dermal fibroblasts as a predictive tool of the toll-like receptor 4 response pathway and its development in Holstein heifers

The innate immune system comprises the host's first line of defense against invading pathogens, and variation in the magnitude of this response between animals has been shown to affect susceptibility to mastitis. The toll-like receptor (TLR) family of proteins initiates the response to invading bacteria, specifically with TLR4 recognizing lipopolysaccharide (LPS) of gram-negative microbes. The underlying genetic variation in the TLR4 pathway leading to differential response is not well understood; therefore, the objective of this work was to determine the efficacy in which the response to LPS by dermal fibroblasts could be used to predict the actual systemic response of that animal to an intravenous endotoxin challenge. To accomplish this, dermal fibroblasts were isolated from 15 Holstein heifers at 5, 11, and 16 mo of age and exposed to either LPS or IL-1β; then, the production of IL-8 in medium was quantified by ELISA. Animals were ranked based upon the magnitude of the fibroblast IL-8 response, and 8 heifers were selected [4 low responders (LR) and 4 high responders (HR)] for challenge with an intravenous bolus dose (0.5 μg/kg of body weight) of LPS. Overall, between-animal variation in fibroblast IL-8 production following LPS or IL-1β was high, indicating appreciable differences in the TLR4 pathway of the animals. Ranking of the fibroblast responses was consistent across the 3 sampling times for each animal; however, the absolute response increased, and the age at which the fibroblasts were obtained was consistent with the potential for age-related changes in cell function to affect immune function processes. Following systemic LPS challenge, HR heifers had higher plasma concentrations of tumor necrosis factor-α and IL-8 than LR heifers. However, LR heifers had a stronger febrile response than HR heifers. The use of dermal fibroblasts under laboratory conditions appears to represent a practical model for predicting the innate immune response in vivo and could act as an important tool in mapping genetic differences of the TLR4 pathway.     

黑米花色苷矢车菊素-3-O-β-葡萄糖苷对脂多糖诱导的人THP-1单核细胞炎症损伤的保护作用

单核细胞介导的炎症反应在动脉粥样硬化发生和发展过程中起关键作用。花色苷是一种具有多种生物学活性的多酚类黄酮化合物,富含于各种深色的蔬菜、水果及谷类中,其中矢车菊素-3-O-β-葡萄糖苷（cyanidin-3-O-β-glucoside,Cy-3-g）是花色苷中重要的单体,本研究旨在探讨黑米来源的Cy-3-g对脂多糖（lipopolysaccharide,LPS）诱导的人单核白血病细胞（Tohoku hospital pediatrics-1,THP-1）炎症损伤的作用及可能的分子机制。采用乙醇-盐酸溶液浸提、大孔树脂吸附洗脱等步骤得到黑米花色苷粗提物,然后用中压液相层析联合紫外检测提取得到纯化的Cy-3-g（纯度>96.5%）。用不同质量浓度（0、0.10、0.25μg/mL和0.50μg/mL）Cy-3-g与THP-1细胞共孵育4 h,然后加入LPS（质量浓度50 ng/mL）与细胞继续孵育48 h,用酶联免疫吸附试验法测定培养液中白细胞介素-1β(interleukin-1β,IL-1β)、IL-6、IL-8、IL-10和肿瘤坏死因子-α(tumor necrosis fac...     

The nutritional supplement Active Hexose Correlated Compound (AHCC) has direct immunomodulatory actions on intestinal epithelial cells and macrophages involving TLR/MyD88 and NF-κB/MAPK activation

Active Hexose Correlated Compound (AHCC) is an immunostimulatory nutritional supplement. AHCC effects and mechanism of action on intestinal epithelial cells or monocytes are poorly described. AHCC was added to the culture medium of intestinal epithelial cells (IEC18 and HT29 cells) and monocytes (THP-1 cells) and assessed the secretion of proinflammatory cytokines by ELISA. Inhibitors of NFκB and MAPKs were used to study signal transduction pathways while TLR4 and MyD88 were silenced in IEC18 cells using shRNA. It was found that AHCC induced GROα and MCP1 secretion in IEC18 and IL-8 in HT29 cells. These effects depended on NFκB activation, and partly on MAPKs activation and on the presence of MyD88 and TLR4. In THP-1 cells AHCC evoked IL-8, IL-1β and TNF-α secretion. The induction of IL-8 depended on JNK and NFκB activation. Therefore, AHCC exerts immunostimulatory effects on intestinal epithelial cells and monocytes involving TLR4/MyD88 and NFκB/MAPK signal transduction pathways.     

沙葱总黄酮水洗组分的体外抗炎活性

本实验在体外应用脂多糖（lipopolysaccharides,LPS）诱导小鼠腹腔巨噬细胞建立炎症模型的基础上,探讨沙葱总黄酮水洗组分的体外抗炎活性。应用CCK-8法检测0、50、100、200、400、800 μg/mL沙葱总黄酮水洗组分对小鼠腹腔巨噬细胞增殖活力的影响;将细胞分为空白对照组、LPS应激模型组及不同质量浓度沙葱总黄酮水洗组分预处理组,采用Griess法及酶联免疫吸附测定法分别测定各处理组细胞上清液中NO浓度和肿瘤坏死因子-α（tumor necrosis factor-α,TNF-α）、白细胞介素（interleukin,IL）-1β、IL-6、IL-10的质量浓度,反转录实时荧光定量聚合酶链式反应法检测各处理组细胞中诱导型一氧化氮合酶（inducible nitric oxide synthase,iNOS）、TNF-α、IL-1β、IL-6、IL-10、髓样分化蛋白（myeloid differential protein,MyD）88、核因子 κB（nuclear factor κB,NF-κB）mRNA的表达水平。结果显示：与对照组相比,沙葱总黄酮水洗组分在50～800 μg/mL时对小鼠腹腔巨噬细胞无明显细胞毒性作用。与LPS应激模型组相比,沙葱总黄酮水洗组分能够极显著抑制促炎介质NO、TNF-α、IL-1β、IL-6质量浓度及其mRNA的表达（P＜0.01或P＜0.001）;高度显著提高抗炎细胞因子IL-10质量浓度及其mRNA的表达（P＜0.001）,且呈剂量依赖效应;极显著降低MyD88、NF-κB mRNA的表达水平（P＜0.01或P＜0.001）。由此得出,沙葱总黄酮水洗组分对LPS诱导的小鼠腹腔巨噬细胞具有抗炎作用,其抗炎活性可能是通过抑制促炎性介质NO、TNF-α、IL-1β、IL-6的分泌并提高抗炎性细胞因子IL-10的质量浓度实现的,其作用机制可能与NF-κB信号通路有关。     

油橄榄叶醇提取物对D-半乳糖胺/脂多糖致小鼠急性肝损伤的保护作用及其作用机制

研究油橄榄叶醇提取物(OLME)对D-半乳糖胺/脂多糖诱导小鼠肝损伤的保护作用。昆明种小鼠按体质量随机分为6组,即空白对照组、模型对照组、阳性对照组(联苯双酯200 mg/kg·d)、OLME低、中、高剂量组(200、400、800 mg/kg·d)。每天给药1次,连续给药14 d,末次给药1 h后,除正常组外其余各组用600 mg/kg·BW D-半乳糖胺和40 μg·kg-1脂多糖腹腔注射以复制小鼠急性肝损伤模型,末次给药12 h后,摘眼球取血,取材。用生化法测定小鼠血清中谷氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)活性,用试剂盒测定各组小鼠肝匀浆中超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性、丙二醛(MDA)含量、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)等炎性因子的表达水平以及半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)和半胱氨酸天冬氨酸蛋白酶-8(Caspase-8)活性。与模型组比较,OLME中高剂量组小鼠血清中ALT和AST活力显著降低(p<0.05),肝组织中MDA、TNF-α、IL-1β和IL-6含量显著降低而SOD活力显著升高(p<0.05),但OLME对GSH-Px改善作用不明显,仅OLME高剂量有一定效果;OLME低、中、高剂量均能显著降低caspase-3和caspase-8活性(p<0.05)。OLME对D-半乳糖胺/脂多糖诱导的小鼠急性肝损伤具有较好的保护作用。     

CRISPR-Cas9–mediated knockout of TLR4 modulates Mycobacterium avium ssp. paratuberculosis cell lysate–induced inflammation in bovine mammary epithelial cells

Toll-like receptor 4 (TLR4) is a pattern-recognition receptor involved in the recognition of microbial pathogens and host alarmins. Ligation to TLR4 initiates a signaling cascade that leads to inflammation. Polymorphisms in bovine TLR4 have been associated with Mycobacterium avium ssp. paratuberculosis (MAP) susceptibility and resistance, the cause of Johne's disease, and milk somatic cell score, a biomarker of mastitis. Although the contribution of TLR4 to recognition of bacterial lipopolysaccharide (LPS) has been well characterized, its role in MAP recognition is less certain. Clustered regularly interspaced short palindromic repeats–Cas9 mediated gene editing was performed to generate TLR4 knockout (KO) mammary epithelial cells to determine if TLR4 expression is involved in the initiation of the host inflammatory response to MAP cell lysate (5 and 10 µg/mL) and Escherichia coli LPS (5 µg/mL). The absence of TLR4 in KO cells resulted in enhanced expression of key inflammatory genes (TNFA and IL6), anti-inflammatory genes (IL10 and SOCS3), and supernatant cytokine and chemokine levels (TNF-α, IL-6, IL-10, CCL3) in response to the MAP cell lysate (10 µg/mL). However, in response to LPS, the KO cells showed reduced expression of key inflammatory genes (TNFA, IL1A, IL1B, and IL6) and supernatant cytokine levels (TNF-α, IL-6, CCL2, IL-8) as compared with unedited cells. Overall, these results confirm that TLR4 is essential for eliciting inflammation in response to LPS; however, exacerbated gene and protein expression in TLR4 KO cells in response to MAP cell lysate suggests a different mechanism of infection and host response for MAP, at least in terms of how it interacts with TLR4. These novel findings show potential divergent roles for TLR4 in mycobacterial infections, and this may have important consequences for the therapeutic control of inflammation in cattle.     

原儿茶酸通过Toll样受体4/核因子κB途径减轻高脂饮食诱导的肝脏炎症

原儿茶酸（protocatechuic acid,PCA）是花青素在体内的主要代谢产物之一,具有良好的抗炎活性。本实验利用高脂饮食（high fat diet,HFD）诱导C57BL/6J小鼠肝脏炎症,通过灌胃100 mg/（kg mb·d）PCA研究其对小鼠肝脏的保护效果,并通过体外实验进一步研究其潜在机制。体内研究结果表明,PCA干预12 周后,可显著降低HFD诱导C57BL/6J小鼠的体质量和肝脏脂肪含量;血清和肝脏中白细胞介素（interleukin,IL）-1β、IL-6、肿瘤坏死因子α（tumor necrosis factor α,TNF-α）和脂多糖（lipopolysaccharide,LPS）等炎症因子水平均明显降低。体外转录组测序及原代肝细胞和肝脏的免疫印迹分析结果表明,PCA可显著降低Toll样受体4（Toll like receptor 4,TLR4）基因和蛋白的表达,然后通过下调核因子κB（nuclear factor κB,NF-κB）的磷酸化抑制炎症因子（如IL-6）的表达。综上,PCA可有效改善HFD诱导的肝脏炎症,其可能是通过下调TLR4/NF-κB信号通路来实现。