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糖尿病大鼠心肌缺血再灌注细胞炎性坏死机制与NLRP3炎症小体活化的研究
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作者 张秋丽 张中军 《解放军预防医学杂志》 CAS 2020年第3期71-74,共4页
目的探究糖尿病大鼠心肌缺血再灌注细胞炎性坏死机制与NLRP3炎症小体活化的相关性。方法制作糖尿病大鼠模型,将30只大鼠分为糖尿病观察组、对照组,观察组15只大鼠置于高脂饲料饲养,对照组15只大鼠置于普通饲料饲养。喂养3个月后处死大... 目的探究糖尿病大鼠心肌缺血再灌注细胞炎性坏死机制与NLRP3炎症小体活化的相关性。方法制作糖尿病大鼠模型,将30只大鼠分为糖尿病观察组、对照组,观察组15只大鼠置于高脂饲料饲养,对照组15只大鼠置于普通饲料饲养。喂养3个月后处死大鼠后分别在12 h、24 h、36 h、48 h取组织细胞后对各组结果进行统计分析。结果 12 h、24 h、36 h后观察组大鼠组织细胞的caspase-3水平、caspase-1、NLRP3及NF-κB较对照组表达略有上升,差异无统计学意义(P>0.05),48 h后观察组大鼠组织细胞的caspase-3水平、 caspase-1、NLRP3及NF-κB较对照组表达显著上升(P<0.05);通过对ASC检测,凋亡因子也较正常对照组明显上升(P<0.05);观察组血糖、肌酐、24 h尿蛋白均较对照组升高(P<0.05);与对照组比较,观察组血清CK-MB和LDH活性升高、心肌梗死面积百分比pro-caspase-1、IL-1β表达上调(P<0.05)。结论糖尿病大鼠心肌缺血再灌注细胞炎性坏死机制与NLRP3炎症小体活化有关。 展开更多
关键词 糖尿病大鼠 心肌缺血再灌注 细胞炎性 坏死机制 NLRP3炎症小体活化
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鸟苷酸结合蛋白家族在感染性疾病中调控炎症小体活化的研究进展 被引量:2
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作者 全舒婷 焦伟伟 +3 位作者 徐放 孙琳 綦辉 申阿东 《遗传》 CAS CSCD 北大核心 2023年第11期1007-1017,共11页
鸟苷酸结合蛋白(guanylate-binding proteins,GBP)是一类干扰素诱导蛋白,在应对细菌、病毒、衣原体以及寄生虫等病原体感染时,其发挥的作用存在差异,并且影响感染性疾病的发展和结局。目前,研究者发现在细菌等病原体感染引发的细胞自主... 鸟苷酸结合蛋白(guanylate-binding proteins,GBP)是一类干扰素诱导蛋白,在应对细菌、病毒、衣原体以及寄生虫等病原体感染时,其发挥的作用存在差异,并且影响感染性疾病的发展和结局。目前,研究者发现在细菌等病原体感染引发的细胞自主免疫中,GBP蛋白通过影响炎症小体的经典和非经典活化途径调控细胞焦亡。本文对GBP家族成员结构、进化特征以及炎症小体的经典和非经典活化途径进行了介绍,综述了GBP蛋白调控炎症小体活化的相关研究进展,归纳总结了GBP蛋白影响不同病原体感染的作用机制,以期为感染性疾病的发病机制和诊疗提供新的基础研究线索。 展开更多
关键词 鸟苷酸结合蛋白 感染性疾病 炎症小体 炎症小体经典活化途径 炎症小体非经典活化途径
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雷公藤甲素抑制NLRP3炎症小体活化改善高糖诱导的足细胞上皮-间充质转分化 被引量:36
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作者 吴薇 刘不悔 +8 位作者 万毅刚 孙伟 刘莹露 王文文 房其军 涂玥 YEE Hong-yun 袁灿灿 万子玥 《中国中药杂志》 CAS CSCD 北大核心 2019年第24期5457-5464,共8页
基于糖尿病肾病(diabetic kidney disease,DKD)肾组织Nod样受体蛋白3(Nod-like receptor protein 3 inflammasome,NLRP3)炎症小体活化的调控机制而探讨雷公藤有效成分——雷公藤甲素(triptolide,TP)在体外改善高糖(high glucose,HG)诱... 基于糖尿病肾病(diabetic kidney disease,DKD)肾组织Nod样受体蛋白3(Nod-like receptor protein 3 inflammasome,NLRP3)炎症小体活化的调控机制而探讨雷公藤有效成分——雷公藤甲素(triptolide,TP)在体外改善高糖(high glucose,HG)诱导足细胞上皮-间充质转分化(epithelial-mesenchymal transition,EMT)的作用。将体外培养的小鼠永生化足细胞分为正常(the normal,N)组、HG组、低剂量TP(the low dose of TP,L-TP)组、高剂量TP(the high dose of TP,H-TP)组以及甘露醇(the mannitol,MNT)组。分别进行不同的干预,即N组加入5 mmol·L^-1D-葡萄糖(D-glucose,DG),HG组加入30 mmol·L^-1HG,L-TP组加入30 mmol·L^-1HG+5μg·L^-1TP,H-TP组加入30 mmol·L^-1HG+10μg·L^-1TP,MNT组加入5 mmol·L^-1DG+24.5mmol·L^-1MNT。在干预后的不同时间点(24,48,72 h),首先,观察HG或TP对足细胞增殖活性的影响;其次,检测足细胞上皮细胞标志性分子nephrin和ZO-1、间充质细胞标志性分子Ⅰ型胶原(collagenⅠ)和纤维连接蛋白(fibronectin,FN)的蛋白表达水平;最后,检测足细胞NLRP3炎症小体活化关键信号分子NLRP3,凋亡相关斑点样蛋白(apoptosis-associated speck-like protien,ASC)以及下游效应蛋白caspase-1、白介素(interleutin,IL)-1β、IL-18的蛋白表达水平。结果表明,对于体外培养的足细胞,HG能引起nephrin,ZO-1蛋白表达水平下调,collagenⅠ,FN蛋白表达水平上调,诱导其发生EMT;还能引起NLRP3,ASC以及caspase-1,IL-1β,IL-18蛋白表达水平上调,诱导其NLRP3炎症小体活化。此外,L-TP或H-TP与HG联合干预足细胞能恢复nephrin,ZO-1蛋白表达水平,抑制collagenⅠ,FN蛋白表达水平,改善EMT;还能下调NLRP3,ASC蛋白表达水平,抑制NLRP3炎症小体活化,并减少其下游效应分子caspase-1,IL-1β,IL-18蛋白表达水平。总之,HG在体外能激活NLRP3炎症小体而诱导足细胞EMT;TP在适当的剂量范围内能抑制NLRP3炎症小体活性而改善足细胞EMT,这可能是TP保护DKD足细胞炎症性损伤的关键分子机制之一。 展开更多
关键词 糖尿病肾病 雷公藤甲素 足细胞 NLRP3炎症小体活化 上皮-间充质转分化
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α-烯醇化酶蛋白抗原的表达与血管相关疾病及肿瘤发生的关系 被引量:1
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作者 刘逸夫 卢一寒 李静 《中国免疫学杂志》 CAS CSCD 北大核心 2020年第12期1508-1511,共4页
α-烯醇化酶(ENO1)参与血管相关疾病的发生发展以及恶性肿瘤细胞的演变和转移,尤其在血管内皮的促炎激活、功能障碍以及自身免疫病微小血管的损害过程发挥重要作用。本文从4个方面分别综述:血管内皮细胞及相关免疫细胞表面的ENO1参与介... α-烯醇化酶(ENO1)参与血管相关疾病的发生发展以及恶性肿瘤细胞的演变和转移,尤其在血管内皮的促炎激活、功能障碍以及自身免疫病微小血管的损害过程发挥重要作用。本文从4个方面分别综述:血管内皮细胞及相关免疫细胞表面的ENO1参与介导炎症活化,引发血管相关疾病;在低氧条件下,HIF-1α通过诱导ENO1表达参与血管生成;ENO1通过翻译后修饰参与血管相关疾病发生发展;ENO1作为毒性因子增加血管的通透性引起血管相关疾病。 展开更多
关键词 烯醇化酶 内皮细胞 炎症活化 低氧诱导因子
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Lipopolysaccharide-induced cerebral inflammatory damage and the therapeutic effect of platelet activating factor receptor antoganist
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作者 刘文超 丁文龙 +2 位作者 顾红玉 陈明峰 胡金家 《Neuroscience Bulletin》 SCIE CAS CSCD 2007年第5期271-276,共6页
Objective To investigate lipopolysaccharide (LPS) induced acute cerebral inflammatory damage and the therapeutic effect of ginkgolide B (BN52021). Methods Thirty Sprague-Dawley rats were randomly divided into 3 gr... Objective To investigate lipopolysaccharide (LPS) induced acute cerebral inflammatory damage and the therapeutic effect of ginkgolide B (BN52021). Methods Thirty Sprague-Dawley rats were randomly divided into 3 groups (n = 10 for each group): Control group, Model group and Treatment group (treated with BN52021). LPS were injected into the fourth ventricle of rat to make a neuroinflammatory murine model. Morris water maze was used to detect the learning and memory ability of rats; changes of synapse number and subcellular ultrastructures were observed under a transmission electron microscope; OX-42 positive microglia in the brain was detected by immunohistochemical method. Results The average escape latency in the Treatment group were significantly shortened than that in the Model group; and the percentage of swimming distance traveled in platform quadrant accounting for total distance increased markedly. The rough endoplasmic reticulum and polyribosomes in the Treatment group were more than that in the Model group, but the number of synapses seemed to have no obvious change. The number of OX-42 positive microglia in the Treatment group decreased markedly than that in the Model group, and the grey density of OX-42-positive cells increased significantly. Conclusion LPS can induce inflammatory damages to the brain, but the damage could be antagonized by BN52021. Platelet activating factor receptor antagonist may offer an effective therapy for neurodegeneration diseases. 展开更多
关键词 brain inflammation platelet activating factor ginkgolide B ULTRASTRUCTURE MICROGLIA
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Inflammation-and stress-related signaling pathways in hepatocarcinogenesis 被引量:19
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作者 Hayato Nakagawa Shin Maeda 《World Journal of Gastroenterology》 SCIE CAS CSCD 2012年第31期4071-4081,共11页
It has been established that cancer can be promoted and exacerbated by inflammation.Hepatocellular carcinoma(HCC) is the fifth most common cancer worldwide,and its long-term prognosis remains poor.Although HCC is a co... It has been established that cancer can be promoted and exacerbated by inflammation.Hepatocellular carcinoma(HCC) is the fifth most common cancer worldwide,and its long-term prognosis remains poor.Although HCC is a complex and heterogeneous tumor with several genomic mutations,it usually develops in the context of chronic liver damage and inflammation,suggesting that understanding the mechanism(s) of inflammation-mediated hepatocarcinogenesis is essential for the treatment and prevention of HCC.Chronic liver damage induces a persistent cycle of necroinflammation and hepatocyte regeneration,resulting in genetic mutations in hepatocytes and expansion of initiated cells,eventually leading to HCC development.Recently,several inflammation-and stress-related signaling pathways have been identified as key players in these processes,which include the nuclear factor B,signal transducer and activator of transcription,and stress-activated mitogen-activated protein kinase pathways.Although these pathways may suggest potential therapeutic targets,they have a wide range of functions and complex crosstalk occurs among them.This review focuses on recent advances in our understanding of the roles of these signaling pathways in hepatocarcinogenesis. 展开更多
关键词 Hepatocellular carcinoma INFLAMMATION Nuclear factor-~B Mitogen-activated protein kinase Signal transducer and activator of transcription c-JunNH2-terminal kinase P38 Transforming growth factor-activated kinase 1 Apoptosis signal-regulating kinase 1
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Assessing the therapeutic impact of Qianjinba polysaccharide in a rheumatoid arthritis murine model
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作者 Nan Zhang Zhimin Liu +3 位作者 Xuanmei Yang Shuang Li Yiwen Gao Haiguang Qin 《Journal of Chinese Pharmaceutical Sciences》 CAS CSCD 2024年第8期705-713,共9页
Qianjinba is primarily cultivated in the southern regions of China and finds extensive use in traditional Chinese medicine(TCM)for conditions such as rheumatism,arthralgia,and gynecological ailments.It has been offici... Qianjinba is primarily cultivated in the southern regions of China and finds extensive use in traditional Chinese medicine(TCM)for conditions such as rheumatism,arthralgia,and gynecological ailments.It has been officially recognized as a protected variety of TCM by the state.The aim of this study was to investigate the therapeutic potential of Qianjinba polysaccharide(QJBDT)in treating rheumatoid arthritis(RA)in mice,along with a preliminary exploration of its mechanisms for inhibiting RA in these animals.Kunming mice(KM)were randomly divided into several groups,including a normal group,a model group(LPS group),low-dose,medium-dose,and high-dose QJBDT groups,as well as a positive control group(TGP group),each consisting of 10 mice.To induce inflammation and create an RA model,type II collagen was injected into the right hind foot joint.Following a 7-day modeling period,various concentrations of QJBDT and the positive control drug total glycoside of peony were administered via gavage once a day for 21 consecutive days.Throughout the study,we monitored and recorded the mice's weight,measured foot swelling,and assessed the arthritis index on a weekly basis.We also conducted pathological examinations of joint tissues and analyzed the signal pathway of p38 mitogen-activated protein kinase(MAPK)as well as the protein expression of nuclear factor NF-κB in the mice’s right foot joint tissues.Additionally,we employed ELISA to detect the levels of interleukin-β(IL-β),IL-17,and tumor necrosis factor-α(TNF-α)in the mice’s serum.The results of this study revealed that QJBDT effectively reduced the degree of foot swelling and the arthritis index in collagen-induced arthritis mice while improving their weight loss(P<0.05).Furthermore,it alleviated the pathological damage observed in the mice’s joints.Notably,the expression of transcription factors p38 and NF-κB proteins was down-regulated(P<0.05),and the levels of inflammatory cytokines IL-β,IL-17,and TNF-αin the mice’s serum were decreased(P<0.05).In conclusion,this study demonstrated that polysaccharides could inhibit the expression of transcription factors p38 and NF-κB,reduce the production of inflammatory factors,and alleviate the progression of RA to a certain extent. 展开更多
关键词 Qianjinba polysaccharide Rheumatoid arthritis Inflammatory factors p38 Mitogen activated protein kinase signaling pathway NF-ΚB
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高血压病患者外周血树突状细胞亚群的变化
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作者 华经海 傅强 +5 位作者 李志梁 刘亚杰 靳文 陶丹萍 曹龙兴 刘鹏 《热带医学杂志》 CAS 2011年第4期408-410,417,共4页
目的研究高血压病患者外周血树突状细胞(DCs)的表达情况及其在高血压病发生发展过程中的作用。方法用流式细胞仪四色荧光标记技术检测29例高血压病(HT)患者(实验组)及31例非高血压患者(对照组)外周血树突状细胞亚群的比例及数量,评价组... 目的研究高血压病患者外周血树突状细胞(DCs)的表达情况及其在高血压病发生发展过程中的作用。方法用流式细胞仪四色荧光标记技术检测29例高血压病(HT)患者(实验组)及31例非高血压患者(对照组)外周血树突状细胞亚群的比例及数量,评价组间差异,并分析高血压病患者外周血浆细胞样树突状细胞(pDC)与血压(blood pressure,BP)的关系。结果高血压病(HT)患者与血压正常患者相比,外周血中髓样树突状细胞(mDC)比例[(7.917±4.296)‰比(8.18±5.669)‰]及绝对数[(6.971±2.115)×107/L比(7.123±5.387)×107/L]均降低,但差异无统计学意义(P>0.05)。而浆细胞样树突状细胞(pDC)比例[(1.239±0.669)‰比(1.897±0.859)‰]及绝对数[(1.794±2.244)×107/L比(2.819±4.997)×107/L]明显升高,且差异有统计学意义(P<0.05),高血压病患者的外周pDC数量与收缩压(SBP)、舒张压(DBP)均成呈正相关关系(r=0.424及0.487,P<0.05),pDC比例与SBP、DBP无明显相关(P>0.05)。结论高血压病的发生发展中存在着炎症反应和免疫活化,树突状细胞可能在该过程中发挥一定的作用。 展开更多
关键词 高血压病 树突细胞 炎症反应与免疫活化
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Influence of Tuina plus oxiracetam on serum inflammatory factors and oxidative stress in mild vascular dementia patients 被引量:1
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作者 GU Nan FAN Yuexian +6 位作者 ZHOU Ling ZHANG Yan BAI Weijie LI Yanfeng YANG Liyun LI Jinlong HONG Jue 《Journal of Acupuncture and Tuina Science》 CSCD 2022年第4期273-280,共8页
Objective To observe the clinical efficacy of Tuina(Chinese therapeutic massage)plus oxiracetam in treating mild vascular dementia(VD)and seek its underlying mechanism.Methods Ninety-six patients with mild VD were ran... Objective To observe the clinical efficacy of Tuina(Chinese therapeutic massage)plus oxiracetam in treating mild vascular dementia(VD)and seek its underlying mechanism.Methods Ninety-six patients with mild VD were randomized into an observation group and a control group,with 47 cases in the observation group and 49 cases in the control group.The control group received oral oxiracetam capsules for treatment,and the observation group was given additional Tuina treatment.Before and after treatment,the mini-mental state examination(MMSE)was adopted to assess the patient’s cognitive function;the activities of daily living(ADL)scale was used to evaluate their ability to conduct daily activities;changes in the serum inflammatory factors and oxidative stress indicators were also detected.Results After treatment,the serum content of malondialdehyde(MDA)decreased in both groups(P<0.05)and was lower in the observation group than in the control group(P<0.05);the serum contents of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)increased in both groups(P<0.05)and were higher in the observation group than in the control group(P<0.05);the serum contents of interleukin(IL)-1,tumor necrosis factor(TNF)-α,IL-6,and IL-8 declined in both groups(P<0.05)and were lower in the observation group than in the control group(P<0.05).After the intervention,the levels of systolic velocity(Vs)and mean velocity(Vm)of the middle cerebral artery elevated,and the pulsatility index(PI)dropped in patients in the two groups,showing significant intra-group differences(P<0.05);the levels of Vs and Vm in the observation group were higher than those in the control group,and the PI was lower in the observation group than in the control group,showing significant between-group differences(P<0.05).The MMSE and ADL scores increased in both groups after the intervention(P<0.05)and were higher in the observation group than in the control group(P<0.05).Conclusion In the treatment of mild VD,Tuina plus oxiracetam can improve the cerebral blood supply,ADL,and cognitive function;the mechanism may be associated with the reduction of oxidative stress damages and inflammatory reactions. 展开更多
关键词 TUINA MASSAGE Cognitive Dysfunction Dementia Vascular Activities of Daily Living Oxidative Stress Inflammatory Factors
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Effects of Suxiao Jiuxin Pill (速效救心丸) on Oxidative Stress and Inflammatory Response in Rats with Experimental Atherosclerosis 被引量:8
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作者 李春深 曲竹秋 +4 位作者 王莎莎 郝旭雯 张秀琴 关晶 韩霏 《Journal of Traditional Chinese Medicine》 SCIE CAS CSCD 2011年第2期107-111,共5页
Objective: To observe the preventive role of Suxiao Jiuxin Pill (SX速效救心丸) on atherosclerosis (AS) and to probe into the mechanism in the atherosclerosis rat model. Methods: The AS rat model was established by a h... Objective: To observe the preventive role of Suxiao Jiuxin Pill (SX速效救心丸) on atherosclerosis (AS) and to probe into the mechanism in the atherosclerosis rat model. Methods: The AS rat model was established by a high fat diet and a large dose of calcium (vitamin D3, 0.6 million U/kg, i.p, once). Sixty healthy male adult Sprague-Dawlay (SD) rats were randomly divided into 6 groups, a normal control group (N), a model group (M), a SX low dose group (SXL), a SX middle dose group (SXM), a SX high dose group (SXH), and an atorvastatin group (ATO) (n=10 in each group). The rats in the treatment groups were given with the specific drugs from the first day by oral administration, and the normal control group and the model group were given with normal saline for 12 weeks. Afterwards, the content of malondialdehyde (MDA), the activity of superoxide dismutase (SOD) and the content of oxidized low density lipoprotein (ox-LDL) in the serum were detected. In addition, the expression of peroxisome proliferator-activated receptor γ (PPARγ) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) proteins were tested by Western-blot method. Results: The serum ox-LDL and MDA level significantly decreased, SOD activity increased in the SX middle, high dose groups and the atorvastatin group compared to the model group (all P<0.05). While the expression of PPARγ and NF-κb proteins significantly decreased in the SX low, middle, high dose groups and the atorvastatin group compared to the model group (all P<0.01), with the best effect in the SX high dose group .These results indicate that SX could elevate the activity of serum SOD, decrease serum level of MDA and ox-LDL, and reduce the expression of PPARγ and NF-κB proteins. Conclusion: SX plays an important role in anti-inflammation and inhibition of oxidative stress, which possibly are the mechanism of its preventing and treating atherosclerosis. 展开更多
关键词 ATHEROSCLEROSIS RATS Suxiao Jiuxin Pill oxidized low density lipoprotein MALONDIALDEHYDE superoxide dismutase
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