旋覆代赭汤对反流性食管炎大鼠模型TLR4/NF-κB的影响

目的观察旋覆代赭汤对反流性食管炎(RE)模型大鼠食管黏膜与脂多糖(LPS)、Toll样受体4(TLR4)、核因子κB(NF-κB)表达的影响。方法将60只雄性Wistar大鼠按随机数字表法分为正常对照组、模型组、旋覆代赭汤组(简称中药组,9.89 g/kg)、西药(奥美拉唑+莫沙比利,2.58 mg/kg)组,每组15只。除正常对照组外大鼠采用“4.2 mm幽门夹+2/3胃底结扎术”制备酸碱混合反流RE大鼠模型。术后第7天予相应药物干预,持续干预14天。利用光学显微镜观察大鼠食管下段黏膜组织形态学变化;应用ELISA法检测定外周血中LPS含量;采用Western Blot法与RT-PCR法检测食管黏膜组织中TLR4、NF-κB蛋白和基因表达。结果与正常对照组比较,模型组大鼠食管黏膜镜下损伤最为严重,食管黏膜呈炎性改变,可见急慢性炎细胞浸润,病理积分和外周血中LPS含量升高(P<0.05),食管组织中TLR4、NF-κB蛋白和基因表达升高(P<0.05)。与模型组比较,中药组、西药组病理积分和外周血中LPS含量降低(P<0.05),食管组织中TLR4、NF-κB蛋白和基因表达亦明显降低(P<0.05)。结论旋覆代赭汤能够减轻RE模型大鼠食管黏膜的损伤,抑制TLR4、NF-κB的表达,促进食管黏膜损伤的恢复。     

Overview of the microbiota in the gut-liver axis in viral B and C hepatitis

Viral B and C hepatitis are a major current health issue, both diseases having a chronic damaging effect on the liver and its functions. Chronic liver disease can lead to even more severe and life-threatening conditions, such as liver cirrhosis and hepatocellular carcinoma. Recent years have uncovered an important interplay between the liver and the gut microbiome: the gut-liver axis. Hepatitis B and C infections often cause alterations in the gut microbiota by lowering the levels of ‘protective’ gut microorganisms and, by doing so, hinder the microbiota ability to boost the immune response. Treatments aimed at restoring the gut microbiota balance may provide a valuable addition to current practice therapies and may help limit the chronic changes observed in the liver of hepatitis B and C patients. This review aims to summarize the current knowledge on the anato-functional axis between the gut and liver and to highlight the influence that hepatitis B and C viruses have on the microbiota balance, as well as the influence of treatments aimed at restoring the gut microbiota on infected livers and disease progression.     

虫草素联合谷氨酰胺对LPS诱导的脓毒症大鼠炎症失衡及肝肺病理变化的影响

目的　研究虫草素（cordycepin,Cop）联合谷氨酰胺（glutamine,Gln）对脂多糖（lipopolysaccharides,LPS）诱导的脓毒症大鼠炎症失衡和肝肺病理变化的影响及其可能机制。 方法　将大鼠按体重随机分为5组：对照组、模型组（LPS组）、LPS+Cop组、LPS+Gln组和LPS+Cop+Gln组,腹腔注射LPS（5 mg/kg）诱导建立脓毒症大鼠模型。ELISA检测外周血中炎症因子IL-6、TNF-α、IL-1β和IL-10的含量;HE染色观察肝肺组织的病理损伤情况;TUNEL染色观察肝肺组织的细胞凋亡情况;Western blot检测肝肺组织中Caspase-3表达水平及NF-κB p65的磷酸化情况 。 结果　LPS+Cop组、LPS+Gln组和LPS+Cop+Gln组均能逆转LPS诱导的促炎因子（IL-6、TNF-α、IL-1β）的高表达和抗炎因子（IL-10）的低表达（P<0.05）,减轻病理损伤,抑制细胞凋亡（P<0.05）,降低凋亡蛋白Caspase-3高表达（P<0.05）,下调NF-κB p65的磷酸化水平（P<0.05）。 结论　在LPS诱导的脓毒症大鼠模型中,虫草素联合谷氨酰胺能有效改善其炎症失衡和肝肺病理变化。     

中间普氏菌内毒素刺激前后下调人牙周膜细胞表达基因的研究

目的 :研究中间普氏菌内毒素刺激前后牙周膜细胞下调表达基因。方法 :应用点样数 5 12点的基因芯片分析中间普氏菌内毒素刺激前后牙周膜细胞下调表达基因。结果 :研究发现中间普氏菌内毒素刺激牙周膜细胞后 8条下调基因 ,包括转录调控基因、凋亡相关基因和受体基因。结论 :中间普氏菌内毒素刺激牙周膜细胞后 ,可引起部分基因表达下调 ,从而影响牙周膜细胞正常的生理功能     

脂多糖刺激牙龈成纤维细胞产生白细胞介素11、6的研究

目的观察牙龈卟啉单胞菌（Porphyromonas gingivalis，Pg）、伴放线放线杆菌（Actinobacillus actinomycetemcomitans，Aa）、大肠杆菌（Escherichia coli，Ec）的脂多糖（lipopolysacchrides，LPS）刺激人牙龈成纤维细胞（human gingival fibroblasts，HGF）合成白细胞介素（interleukin，IL）-11和IL-6的能力，并了解内源性前列腺素是否介导IL-11和IL-6的产生。方法将3种浓度的LPS（0．1、1、10mg／L）分别作用于体外培养的HGF 24h，另外在10mg／L的LPS中加入10^-6 moL／L的吲哚美辛后再分别刺激HGF 24h，ELISA法检测HGF上清液中IL-11和IL-6含量的变化。结果Aa-，Ec-LPS（10mg／L）和Pg-LPS（1、10mg／L）刺激HGF后IL-11水平显著提高；Pg-，Ec-LPS（0．1、1、10mg／L）和Aa-LPS（1、10ms／L）刺激HGF产生IL-6的水平明显增高；这些作用均受到吲哚美辛的抑制作用。结论LPS使HGF产生IL-11和IL-6的水平明显增加，并受到内源性前列腺素的正向调控。     

Lidocaine attenuates lipopolysaccharide-induced inflammatory responses in microglia

Background

Lidocaine has been used as a local anesthetic with anti-inflammatory properties, but its effects on neuroinflammation have not been well defined. In the present study, we investigated the prophylactic effects of lidocaine on lipopolysaccharide (LPS)-activated microglia and explored the underlying mechanisms.

Materials and methods

Microglial cells were incubated with or without 1 μg/mL LPS in the presence or absence of lidocaine, a p38 mitogen–activated protein kinase (p38 MAPK) inhibitor (SB203580), a nuclear factor-kappa B (NF-κB) inhibitor (pyrrolidine dithiocarbamate), or small interfering RNA. The protein and expression levels of inflammatory mediators, such as monocyte chemotactic protein 1, nitric oxide, prostaglandin E₂, interleukin 1β, and tumor necrosis factor α were measured using enzyme-linked immunosorbent assays and real-time polymerase chain reaction. The effect of lidocaine on NF-κB and p38 MAPK activation was evaluated using enzyme-linked immunosorbent assays, Western blot analysis, and electrophoretic mobility shift assay.

Results

Lidocaine (≥2 μg/mL) significantly inhibited the release and expression of nitric oxide, monocyte chemotactic protein 1, prostaglandin E₂, interleukin 1β, and tumor necrosis factor α in LPS-activated microglia. Treatment with lidocaine also significantly inhibited the phosphorylation of p38 MAPK and the nuclear translocation of NF-κB p50/p65, increased the protein levels of inhibitor kappa B-α. Furthermore, our study shows that the LPS-induced release of inflammatory mediators was suppressed by SB203580, pyrrolidine dithiocarbamate, and small interfering RNA.

Conclusions

Prophylactic treatment with lidocaine inhibits LPS-induced release of inflammatory mediators from microglia, and these effects may be mediated by blockade of p38 MAPK and NF-κB signaling pathways.     

去甲肾上腺素减轻脂多糖所致内皮细胞损伤

目的:探讨去甲肾上腺素(norepinephrine,NE)减轻脂多糖(lipopolysaccharides,LPS)对内皮细胞损伤的作用。方法:用100 mg/L LPS诱导人脐静脉血管内皮细胞HUVEC-12损伤,用不同浓度NE处理后,使用realtime PCR及Western blot法检测各组内皮细胞血管内皮型钙黏素(VE-cadherin)表达的变化,ELISA法测定细胞培养上清液中TNF-α、IL-1β、IL-2和IL-10的浓度,活性氧簇(reactive oxygen species,ROS)检测试剂盒检测细胞内的ROS水平。结果:LPS可显著抑制内皮细胞中VE-cadherin m RNA和蛋白的表达水平,同时伴有TNF-α、IL-1β和IL-2升高及IL-10下降,ROS含量明显增加;不同浓度的NE呈剂量依赖性地上调VE-cadherin的m RNA和蛋白表达,减轻细胞内的氧化应激水平,并部分逆转TNF-α、IL-1β、IL-2和IL-10的变化。结论:不同浓度NE能明显逆转LPS造成的内皮细胞损伤,其机制可能与上调VE-cadherin、减轻细胞的氧化应激及炎性介质水平有关。     

原花青素B1与B2抑制脂多糖诱导的BV-2细胞炎症反应作用的比较

目的:比较原花青素二聚体的2种同分异构体——原花青素B1和B2对脂多糖(lipopolysaccharide,LPS)诱导的BV-2细胞炎症反应的抑制作用。方法:体外培养BV-2细胞,MTT法检测原花青素B1与B2对BV-2细胞活力的影响;以1 mg/L的LPS刺激BV-2细胞12 h建立的细胞炎症模型为研究对象,分别采用ELISA法、Transwell趋化实验和Western blot法比较原花青素B1和B2对LPS诱导的BV-2细胞分泌肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)和白细胞介素1β(interleukin-1β,IL-1β)、趋化行为及核因子κB(NF-κB)磷酸化的抑制作用。结果:原花青素B1和B2对BV-2细胞没有毒性。与LPS组比较,原花青素B1和B2均可显著降低LPS诱导的TNF-α和IL-1β的释放及BV-2细胞的趋化作用,并抑制NF-κB的磷酸化。结论:原花青素B1和B2均能抑制LPS诱导的BV-2细胞炎症反应,其作用强度无显著差异。