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Inflammation plays a critical role in the development of ventilator-induced lung injury (VILI). Endoplasmic reticulum (ER) stress is associated with a variety of diseases through the modulation of inflammatory responses. However, little is known about how ER stress is implicated in VILI. In this study, murine mechanical ventilation models were constructed. Total protein and inflammatory cytokines were measured in bronchoalveolar lavage fluid (BALF), and lung tissue injury was assessed by histology. Our data revealed that mice subjected to high tidal ventilation (TV) for 4 h showed more severe pulmonary edema and inflammation than those of mice with spontaneous breathing and low TV-treatment. In addition, the high TV-treated animals upregulated the ER stress markers GRP78, CHOP, p-IRE1α, TRAF2, and p-NF-κB expression at both the mRNA and protein levels in lung tissue. Administration of thapsigargin exacerbated the histological changes, inflammation and expression of GRP78 and CHOP after high TV, but treatment with ER stress and IRE1α kinase inhibitors attenuated the pathological damage and downregulated the high expression of GRP78, CHOP, p-IRE1α, TRAF2, and p-NF-κB, suggesting that ER stress is involved in VILI though the IRE1α/TRAF2/NF-κB signaling pathway in mice. 相似文献
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Robert M. Levy Roman Saikovsky Evgeniya Shmidt Alexander Khokhlov Bruce P. Burnett 《Nutrition Research》2009
Flavocoxid (Limbrel), a proprietary mixture of flavonoid molecules (baicalin and catechin), was tested against a traditional nonsteroidal anti-inflammatory drug, naproxen, for the management of the signs and symptoms of moderate osteoarthritis (OA) in humans. Discomfort and global disease activity were used as the primary end points, and safety assessments were also taken for both treatments as a secondary endpoint. In this double-blind study, 103 subjects were randomly assigned to receive either flavocoxid [500 mg twice daily (BID)] or naproxen (500 mg BID) in a 1-month onset of action trial. Outcome measures included the short Western Ontario and McMaster University Osteoarthritis Index, subject Visual Analogue Scale for discomfort and global response, and investigator Visual Analogue Scale for global response and fecal occult blood. Both flavocoxid and naproxen showed significant reduction in the signs and symptoms of knee OA (P ≤ .001). There were no statistically detectable differences between the flavocoxid and naproxen groups with respect to any of the outcome variables. Similarly, there were no statistically detectable differences between the groups with respect to any adverse event, although there was a trend toward a higher incidence of edema and nonspecific musculoskeletal discomfort in the naproxen group. In this short-term pilot study, flavocoxid was as effective as naproxen in controlling the signs and symptoms of OA of the knee and would present a safe and effective option for those individuals on traditional nonsteroidal anti-inflammatory drugs or cyclooxygenase-2 inhibitors. A low incidence of adverse events was reported for both groups. 相似文献
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同型半胱氨酸对黑质细胞凋亡及NF-κB表达的影响 总被引:3,自引:0,他引:3
目的研究同型半胱氨酸(homocysteine,Hcy)对帕金森(parkinson’s disease,PD)大鼠的黑质细胞的细胞凋亡及NF-κB表达的影响作用。方法100只SD鼠随机分为四组,即正常对照组、6-OHDA组、Hcy组、6-OHDA+Hey组,通过脑立体定向注射6-羟多巴胺建立大鼠PD模型,2小时后同侧脑立体定向注射同型半胱氨酸或生理盐水,采用TUNEL法、免疫组化技术,选择实验后后4h、1d、2d、7d及14d为研究时点,观察黑质细胞凋亡的数量;并检测黑质细胞NF-κB p65的表达情况。结果局部注射同型半胱氨酸能明显增加6-羟基多巴胺引起的黑质细胞凋亡,并增加黑质细胞NF-κB p65的表达,与对照组存在显著性差异(P<0.01)。结论Hcy可以促进6-OHDA引起的黑质细胞凋亡,NF-κBp65的激活可能是机制之一。 相似文献
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NF-κB对尿白蛋白诱导肾小管上皮细胞骨桥蛋白转录的影响 总被引:5,自引:3,他引:2
目的研究NF-κB对尿白蛋白诱导肾小管上皮细胞骨桥蛋白转录的影响。方法去脂的小牛血清白蛋白(BSA)20mg/ml分别加入到体外培养的肾小管上皮细胞和加入NF-κB抑制剂(PDTC)共同培养半小时的肾小管上皮细胞内,EMSA、RT-PCR检测不同时限NF-κB活性、骨桥蛋白mRNA表达情况。结果去脂的小牛血清白蛋白可刺激肾小管上皮细胞内NF-κB活性增加,骨桥蛋白mRNA表达上调,而提前加入NF-κB抑制剂(PDTC)共同培养半小时的肾小管上皮细胞内NF-κB活性、骨桥蛋白mRNA表达明显下降。结论尿白蛋白诱导小管上皮细胞损伤的机制与诱导肾小管上皮细胞内NF-κB活性、骨桥蛋白mRNA增加有关,而且骨桥蛋白转录由NF-κB调控。 相似文献
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《Immunity》2020,52(6):1075-1087.e8
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Nae Yu Kim Jung-Soo Pyo Dong-Wook Kang Seung-Min Yoo 《Pathology, research and practice》2019,215(3):580-585