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【目的】 研究硒蛋白谷胱甘肽过氧化物酶4(glutathione peroxidases 4,GPX4)失活如何参与调控脂多糖(lipopolysaccharide,LPS)诱导的RAW264.7巨噬细胞炎症反应及其潜在的分子机制。【方法】 体外培养RAW264.7巨噬细胞,以DMSO为对照,使用0.1~5.0 μmol/L GPX4抑制剂FIN56处理,通过CCK-8法检测细胞活力和Western blotting检测GPX4蛋白表达水平,确定抑制剂最适浓度。将RAW264.7巨噬细胞分为4组:对照组,添加DMSO培养24 h;FIN56(GPX4抑制剂)组,添加0.5 μmol/L FIN56培养24 h;DMSO-LPS组,DMSO培养24 h后使用LPS (100 ng/mL)刺激3 h;FIN56-LPS组,FIN56培养24 h后使用LPS刺激3 h。各组细胞经培养后,利用荧光探针2',7'-二氯二氢荧光素二乙酸酯(2',7'-dichlorodi-hydrofluorescein diacetate,H2DCFDA)检测细胞内活性氧(reactive oxygen species,ROS)水平,使用试剂盒法检测细胞内丙二醛(malondialdehyde,MDA)水平,分别使用ELISA和荧光定量PCR检测促炎细胞因子白细胞介素1β(interleukin-1β,IL-1β)、白细胞介素6(interleukin-6,IL-6)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)的分泌水平和基因表达量,使用Western blotting法检测Toll样受体4(toll like receptor 4,TLR4)信号通路相关蛋白表达水平。【结果】 与DMSO处理相比,0.5 μmol/L FIN56处理巨噬细胞24 h对细胞活性无显著影响(P>0.05),且显著降低GPX4蛋白表达水平(P<0.05),故选用0.5 μmol/L FIN56用于后续实验。与对照组相比,FIN56和LPS均显著增加了ROS积累(P<0.05),而与DMSO-LPS组相比,FIN56-LPS组ROS水平显著升高(P<0.05)。与对照组相比,LPS可显著增加小鼠巨噬细胞IL-1β、IL-6和TNF-α的mRNA表达量和IL-6含量,以及c-Jun氨基末端蛋白激酶(c-Jun N-terminal protein kinase,JNK)和c-Jun磷酸化水平(P<0.05),而FIN56可显著下调LPS诱导的IL-6的mRNA表达量和含量及JNK和c-Jun磷酸化水平(P<0.05),但对p38蛋白(p38 MAPK,p38)、细胞外调节蛋白激酶(phosphorylate extracellular regulated protein kinases1/2,Erk1/2)蛋白表达水平无显著影响(P>0.05)。【结论】 GPX4失活可有效阻断JNK和c-Jun磷酸化,从而特异性抑制LPS诱导的巨噬细胞的炎症反应。该结果可为以GPX4为靶点研发抗炎治疗策略提供理论依据。  相似文献   
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高精低粗的饲粮结构会引起奶牛瘤胃内乳酸和挥发性脂肪酸浓度升高,瘤胃液pH降低,导致瘤胃内微生物区系发生改变,从而引起瘤胃内异常代谢产物(细菌内毒素、组胺等)增加,甚至引发亚急性瘤胃酸中毒。其中,组胺是机体内重要的炎性介质,高浓度的组胺转运至血液后可引起机体炎症反应,引起奶牛多种疾病,并使奶牛生产性能下降。本文对奶牛瘤胃异常发酵时组胺的产生和转运以及组胺诱导炎性反应的机制进行综述,同时,介绍一些限制组胺生成和转运的方法,为控制和减少组胺对奶牛的危害提供参考。  相似文献   
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The purpose of this study was to investigate the nature of variably sized pigmented foci encountered in fillets of farmed Atlantic salmon, Salmo salar L. The material was sampled on the fillet production line and on salmon farms from fish with an average size of 3 kg from various producers. The fish had been routinely vaccinated by injection. Gross pathology, histology, immunohistochemistry using antisera against major histocompatibility complex (MHC) class II beta chain and transmission electron microscopy (TEM) were used to characterize the changes. Macroscopically, melanized foci were seen penetrating from the peritoneum deep into the abdominal wall, sometimes right through to the skin, and also embedded in the caudal musculature. Histological investigation revealed muscle degeneration and necrosis, fibrosis and granulomatous inflammation containing varying numbers of melano-macrophages. Vacuoles, either empty or containing heterogeneous material, were frequently seen. The presence of abundant MHC class II+ cells indicated an active inflammatory condition. TEM showed large extracellular vacuoles and leucocytes containing homogeneous material of lipid-like appearance. The results showed that the melanized foci in Atlantic salmon fillet resulted from an inflammatory condition probably induced by vaccination. The described condition is not known in wild salmon and in farmed salmon where injection vaccination is not applied.  相似文献   
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ObjectiveTo review the immune response to anesthesia including mechanical ventilation, inhaled anesthetic gases, and injectable anesthetics and sedatives.Study designReview.Methods and databasesMultiple literature searches were performed using PubMed and Google Scholar from spring 2012 through fall 2013. Relevant anesthetic and immune terms were used to search databases without year published or species constraints. The online database for Veterinary Anaesthesia and Analgesia and the Journal of Veterinary Emergency and Critical Care were searched by issue starting in 2000 for relevant articles.ConclusionRecent research data indicate that commonly used volatile anesthetic agents, such as isoflurane and sevoflurane, may have a protective effect on vital organs. With the lung as the target organ, protection using an appropriate anesthetic protocol may be possible during direct pulmonary insults, including mechanical ventilation, and during systemic disease processes, such as endotoxemia, generalized sepsis, and ischemia-reperfusion injury.  相似文献   
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Heart and skeletal muscle inflammation (HSMI) is a disease syndrome of unknown aetiology first observed in farmed Atlantic salmon, Salmo salar, in 1999. In the present study we have demonstrated for the first time that HSMI is an infectious disease. It was induced in Atlantic salmon post-smolts after injection with tissue homogenate from farmed Atlantic salmon previously diagnosed with HSMI. The lesions were also induced in cohabitating salmon given a corresponding injection without tissue homogenate. Six weeks post-challenge the fish that had been injected with tissue homogenate developed a serious epicarditis and myocarditis with mononuclear cell infiltrations in compact and spongy layers of the heart. Similar lesions were found in cohabitants after 10 weeks. The lesions were consistent with samples from field outbreaks of HSMI. No lesions were found in control fish. A viral aetiology is strongly suggested, as no difference in disease induction between an inoculum containing antibiotics and a non-treated inoculum was found. Further investigations are required in order to make conclusions regarding the cause and pathogenesis of HSMI.  相似文献   
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Zargham Khan, M., Muhammad, G., Umar, A. and Ali Khan, S., 1997. A preliminary comparison of plasma fibrinogen concentrations, leukocyte numbers and erythrocyte sedimentation rate as non-specific indicators of inflammatory conditions in buffalo (Bubalis bubalis). Veterinary Research Communications, 21 (4), 265-271The plasma fibrinogen concentration (Fib), total leukocyte count (TLC), neutrophil, lymphocyte and monocyte numbers, and the erythrocyte sedimentation rate (ESR) were determined in 153 buffaloes suffering from different clinical conditions. Fib increased significantly (p < 0.05) in chronic mastitis, pyrexia, pyometra, cutaneous abscesses, tail gangrene and acute indigestion, whereas in most of the other conditions studied it varied non-significantly. TLC increased significantly in chronic mastitis, pyrexia, endometritis, cutaneous abscesses and infected skin wounds. An increase in neutrophils was associated with an increased TLC. Numbers of lymphocytes varied non-significantly in most of the conditions. Monocytes decreased significantly in most of the acute conditions. ESR was significantly elevated in all clinical conditions. Significantly increased mean Fib values in the different conditions varied from 703 ± 119 to 725 ± 140 mg/dl, while the maximum individual value was 1510 mg/dl in a case of cutaneous myiasis. The significantly increased mean TLC ranged from 9.48 ± 2.91 to 11.1 ± 3.5 × 103/µl, while it was 21.7 × 103/µl in a case of meningitis. ESR values in sick buffaloes varied from 57 to 111 mm in the first hour.  相似文献   
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