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川陈皮素调节AMPK/NLRP3信号通路对脂多糖诱导的肾小球系膜细胞炎性损伤的影响
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作者 罗丹 王燕 +1 位作者 丁旭 胡耀 《中药新药与临床药理》 CAS CSCD 北大核心 2024年第2期224-229,共6页
目的探讨川陈皮素(Nobiletin)调节AMP激活的蛋白激酶(AMPK)/NOD样受体蛋白3(NLRP3)信号通路对脂多糖(LPS)诱导的肾小球系膜细胞HBZY-1炎性损伤的影响。方法将HBZY-1细胞分为5组:正常组、LPS组(100 ng·m L^(-1)LPS)、川陈皮素组(100... 目的探讨川陈皮素(Nobiletin)调节AMP激活的蛋白激酶(AMPK)/NOD样受体蛋白3(NLRP3)信号通路对脂多糖(LPS)诱导的肾小球系膜细胞HBZY-1炎性损伤的影响。方法将HBZY-1细胞分为5组:正常组、LPS组(100 ng·m L^(-1)LPS)、川陈皮素组(100 ng·m L^(-1)LPS+40μmol·L^(-1)川陈皮素)、AMPK/NLRP3信号通路抑制剂雷帕霉素组(100 ng·m L^(-1)LPS+0.5μmol·L^(-1)雷帕霉素)、川陈皮素+雷帕霉素组(100 ng·m L^(-1)LPS+40μmol·L^(-1)川陈皮素+0.5μmol·L^(-1)雷帕霉素)。MTT法检测HBZY-1细胞毒性和增殖;ELISA法检测HBZY-1细胞白细胞介素(IL)-1β、IL-6、肿瘤坏死因子α(TNF-α)、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)含量;流式细胞术检测细胞凋亡;Western Blot法检测AMPK/NLRP3信号通路蛋白水平。结果与正常组比较,LPS组CAT、SOD、GSH水平、细胞OD值以及AMPK蛋白水平明显降低(P<0.05),细胞凋亡率、IL-1β、IL-6、TNF-α含量以及NLRP3蛋白水平明显升高(P<0.05)。与LPS组比较,川陈皮素组CAT、SOD、GSH水平、OD值以及AMPK蛋白水平明显升高(P<0.05),细胞凋亡率、IL-1β、IL-6、TNF-α含量以及NLRP3蛋白水平明显下降(P<0.05);而雷帕霉素组以上指标均呈现与川陈皮素组相反的趋势(P<0.05)。与川陈皮素组比较,川陈皮素+雷帕霉素组以上指标均呈现与川陈皮素组相反的趋势(P<0.05)。结论川陈皮素可能通过上调AMPK/NLRP3信号通路减轻LPS诱导的肾小球系膜细胞细胞炎性损伤。下调AMPK/NLRP3信号通路可消除川陈皮素对LPS诱导的肾小球系膜细胞细胞炎性损伤的改善作用。 展开更多
关键词 川陈皮素 AMP激活的蛋白激酶/NOD样受体蛋白3(ampk/nlrp3)信号通路 脂多糖 肾小球系膜细胞 HBZY-1 炎性损伤
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依托咪酯调节AMPK/NLRP3信号通路对急性心肌梗死大鼠心肌损伤的影响
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作者 张化 王艳萍 《广东药科大学学报》 CAS 2024年第2期104-111,共8页
目的探究依托咪酯调节腺苷酸活化蛋白激酶(AMPK)/核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)信号通路对急性心肌梗死(AMI)大鼠心肌损伤的影响。方法取SD大鼠通过结扎左冠状动脉前降支建立AMI模型,随机分为模型组、依托咪酯组、Dorsomorp... 目的探究依托咪酯调节腺苷酸活化蛋白激酶(AMPK)/核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)信号通路对急性心肌梗死(AMI)大鼠心肌损伤的影响。方法取SD大鼠通过结扎左冠状动脉前降支建立AMI模型,随机分为模型组、依托咪酯组、Dorsomorphin组、依托咪酯+Dorsomorphin组,每组12只,另取12只大鼠作为假手术组开胸后不结扎,分组处理后检测各组大鼠心功能、心肌组织病理损伤及纤维化、血清乳酸脱氢酶(LDH)、肌酸磷酸激酶(CPK)、白细胞介素(IL)-1β、IL-6、超氧化物歧化酶(SOD)与丙二醛(MDA)水平、心肌组织IL-1β、IL-6、SOD与MDA水平、心肌组织AMPK/NLRP3通路相关蛋白表达。结果与假手术组相比,模型组大鼠心肌组织呈严重病理损伤,左室舒张末期内径(LVDD)、左室收缩末期内径(LVDS)、心肌胶原容积分数(CVF)、血清LDH、CPK、IL-1β及IL-6水平、心肌组织IL-1β、IL-6及MDA水平、心肌组织NLRP3蛋白表达明显升高(P<0.05),左室射血分数(EF)、血清及心肌组织SOD水平、心肌组织p-AMPK/AMPK明显降低(P<0.05)。与模型组相比,依托咪酯组大鼠心肌组织病理损伤减轻,LVDD、LVDS、心肌CVF、血清LDH、CPK、IL-1β及IL-6水平、心肌组织IL-1β、IL-6及MDA水平、心肌组织NLRP3蛋白表达均降低(P<0.05),EF、血清及心肌组织SOD水平、心肌组织p-AMPK/AMPK升高(P<0.05);Dorsomorphin组大鼠各指标变化趋势与依托咪酯组相反,且Dorsomorphin可减弱依托咪酯对模型组大鼠各指标的作用。结论依托咪酯可通过调控AMPK/NLRP3信号传导而抑制AMI后炎症与氧化应激反应,进而减轻AMI大鼠心肌组织损伤及纤维化,改善其心功能。 展开更多
关键词 依托咪酯 ampk/nlrp3 急性心肌梗死 心肌损伤
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甲基莲心碱通过调节AMPK/mTOR/NLRP3信号通路减轻慢性皮肤溃疡大鼠的炎症反应
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作者 齐淑静 付改霞 齐瑞霞 《东南大学学报(医学版)》 CAS 2024年第1期33-39,共7页
目的:探讨甲基莲心碱(Nef)调节AMP活化蛋白激酶(AMPK)/哺乳动物雷帕霉素靶蛋白(mTOR)/NOD样受体热蛋白结构域相关蛋白3(NLRP3)信号通路对慢性皮肤溃疡(CSU)大鼠炎症反应的影响。方法:将90只大鼠随机分为空白对照组(NC组)、CSU组、Nef组... 目的:探讨甲基莲心碱(Nef)调节AMP活化蛋白激酶(AMPK)/哺乳动物雷帕霉素靶蛋白(mTOR)/NOD样受体热蛋白结构域相关蛋白3(NLRP3)信号通路对慢性皮肤溃疡(CSU)大鼠炎症反应的影响。方法:将90只大鼠随机分为空白对照组(NC组)、CSU组、Nef组、AMPK抑制剂(Compound C)组、Nef+Compound C组,每组18只大鼠。除NC组外的其他各组大鼠通过剪开创口注射氢化可的松以及喷洒金黄色葡萄球菌构建CSU大鼠模型。造模完成后,Nef组和Compound C组分别将20%Nef、10μmol·L^(-1) Compound C与50 mL的20%高渗盐水凝胶混合敷在伤口处,Nef+Compound C组将20%Nef和10μmol·L^(-1) Compound C一起添加到20%高渗盐水凝胶中敷在伤口处,持续治疗2周,NC组、CSU组用等量盐水凝胶处理伤口。观察大鼠皮肤创面愈合情况;ELISA法检测血清白细胞介素(IL)-1β、IL-8、TNF-α水平;水解法检测创面肉芽组织中羟脯氨酸(HyP)水平;HE染色检测肉芽组织病理学变化;Western blotting检测CCL4、CCL2、CXCL12以及AMPK/mTOR/NLRP3信号通路蛋白表达水平。结果:CSU组大鼠可看到新生肉芽组织,并且有大量炎症细胞浸润现象,CSU组较NC组IL-1β、IL-8、TNF-α含量显著升高(P<0.05);与CSU组相比,Nef组创面愈合率、HyP含量、p-AMPK/AMPK蛋白水平显著增加(P<0.05),IL-1β、IL-8、TNF-α含量、CCL2、CXCL12、CCL4、mTOR、NLRP3蛋白水平显著下降(P<0.05),而Compound C组趋势相反(P<0.05);Compound C消除了Nef对CSU大鼠炎症反应的减轻作用。结论:Nef可能通过调控AMPK/mTOR/NLRP3信号通路减轻CSU大鼠炎症反应。 展开更多
关键词 甲基莲心碱 ampk/mTOR/nlrp3信号通路 慢性皮肤溃疡 炎症反应 大鼠
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Amitriptyline inhibits NLRP3 inflammasome activation via the ASM/CE pathway in a cell model of NAFLD 被引量:1
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作者 QIN LIU CHUNYAN NIU +3 位作者 QIANG ZHANG SHIQIN SUN YUE CHEN YONGQIANG SHI 《BIOCELL》 SCIE 2024年第5期759-769,共11页
Background:Nonalcoholic fatty liver disease(NAFLD)is a global health concern with the acid sphingomyelinase(ASM)/ceramide(CE)pathway and the NOD-like receptor family,pyrin domain-containing protein 3(NLRP3)inflammasom... Background:Nonalcoholic fatty liver disease(NAFLD)is a global health concern with the acid sphingomyelinase(ASM)/ceramide(CE)pathway and the NOD-like receptor family,pyrin domain-containing protein 3(NLRP3)inflammasome identified as pivotal players in lipid disorders and inflammation.This study explores the interaction mechanism between the ASM/CE pathway and NLRP3 in NAFLD cell models,aiming to understand the impact of amitriptyline(Ami),an ASM inhibitor,on lipid deposition and hepatocyte injury by regulating the ASM/CE-NLRP3 pathway.Methods:HepG2 and HL-7702 cells were exposed to free fatty acids(FFAs)to establish the NAFLD model.The cells were divided into 5 groups:control group,model group,Ami group,tumor necrosis factoralpha(TNF-α)group,and Ami+TNF-αgroup.Intracellular lipid droplets were visualized using Oil Red O staining,and Western blot analysis quantified ASM,NLRP3,and caspase 1 protein expression.Enzyme linked immunosorbent assay(ELISA)was measured CE and ASM levels,while qRT-PCR assessed mRNA expression.The apoptotic rate was evaluated by flow cytometry(FCM).Results:Following FFAs incubation,significant increases in ASM and CE levels were observed in HepG2 and HL-7702 cells,accompanied by elevated expression of NLRP3,and caspase 1,and IL-1β.TNF-αtreatment further amplified these indicators.Ami demonstrated a reduction in lipid deposition,suppressed ASM/CE pathway activation,downregulated NLRP3 and caspase 1 expression,and improved apoptosis.Additionally,MCC950,a selective inhibitor of the NLRP3,mitigated NLRP3,caspase 1,and IL-1βexpression,alleviating lipid deposition and apoptosis in the NAFLD cell model.Conclusion:The ASM/CE-NLRP3 pathway in NAFLD cells promotes hepatocyte steatosis,inflammation,and cell damage.Ami emerges as a promising therapeutic agent by inhibiting the ASM/CE-NLRP3 pathway,underscoring its potential as a key target for NAFLD treatment. 展开更多
关键词 Nonalcoholic fatty liver disease HEPATOCYTE AMITRIPTYLINE ASM/CE pathway nlrp3 Nonalcoholic steatohepatitis
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Porphyromonas gingivalis Induces Chronic Kidney Disease through Crosstalk between the NF-κB/NLRP3 Pathway and Ferroptosis in GMCs
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作者 Xue LI Chao YAO +2 位作者 Dong-mei LAN Yan WANG Sheng-cai QI 《Current Medical Science》 SCIE CAS 2024年第5期932-946,共15页
Objective Porphyromonas gingivalis(P.gingivalis)is a gram-negative bacterium found in the human oral cavity and is a recognized pathogenic bacterium associated with chronic periodontitis and systemic diseases,includin... Objective Porphyromonas gingivalis(P.gingivalis)is a gram-negative bacterium found in the human oral cavity and is a recognized pathogenic bacterium associated with chronic periodontitis and systemic diseases,including chronic kidney disease(CKD),but the roles and molecular mechanism of P.gingivalis in CKD pathogenesis are unclear.Methods In this study,an animal model of oral P.gingivalis administration and glomerular mesangial cells(GMCs)cocultured with M1-polarized macrophages and P.gingivalis supernatant were constructed.After seven weeks of P.gingivalis gavaged,peripheral blood was collected to detect the changes in renal function.By collecting the teeth and kidneys of mice,H&E staining and IHC were used to analyze the expression of periodontal inflammatory factors in mice,PAS staining was used to analyze glomerular lesions.The supernatant of macrophages was treated with 5%P.gingivalis supernatant.H&E staining,IHC,Western blot and RT-PCR were applied to analyze renal inflammatory factors,macrophage M1 polarization,NF-κB,NLRP3 and ferroptosis changes in vitro.Results We found that oral P.gingivalis administration induced CKD in mice.P.gingivalis supernatant induced macrophage polarization and inflammatory factor upregulation,which triggered the activation of the NF-κB/NLRP3 pathway and ferroptosis in GMCs.By inhibiting the NF-κB/NLRP3 pathway and ferroptosis in GMCs,cell viability and the inflammatory response were partially alleviated in vitro.Conclusion We demonstrated that P.gingivalis induced CKD in mice by triggering crosstalk between the NFκB/NLRP3 pathway and ferroptosis in GMCs.Overall,our study suggested that periodontitis can promote the pathogenesis of CKD in mice,which provides evidence of the importance of periodontitis therapy in the prevention and treatment of CKD. 展开更多
关键词 Porphyromonas gingivalis chronic kidney disease glomerular mesangial cells MACROPHAGES NF-κB/nlrp3 pathway ferroptosis
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Branched-chain fatty acids from goat milk alleviate ulcerative colitis via the TLR4/NF-κB/NLRP3 pathway
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作者 Jiaxin Zhang Jinjing Zhong +7 位作者 Zhengying Cui Yu Shen Yaping Zheng Yu Zhang Chaoxin Man Yanmei Hou Qianyu Zhao Yujun Jiang 《Food Science and Human Wellness》 SCIE CAS CSCD 2024年第6期3624-3632,共9页
Branched-chain fatty acids(BCFAs)are new bioactive fatty acids with anti-inflammatory properties.However,the role of BCFAs in alleviating ulcerative colitis has not been clarified.Herein,we evaluated the protective ef... Branched-chain fatty acids(BCFAs)are new bioactive fatty acids with anti-inflammatory properties.However,the role of BCFAs in alleviating ulcerative colitis has not been clarified.Herein,we evaluated the protective effect of BCFAs from goat milk in mice with colitis induced using dextran sodium sulfate(DSS)and explored the corresponding mechanism.These results show that BCFAs extracted from goat milk can significantly alleviate weight loss in mice,and reduce the disease activity index and the activity of myeloperoxidase while increasing the content of antioxidant enzymes in colon tissue and reducing the oxidation stress response.These data also show that BCFAs can down-regulate the gene and protein expression of the toll-like receptor 4(TLR4)/nuclear factorκB p65(NF-κB p65)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathway,and at the same time significantly reduce the expression of pro-inflammatory factors tumor necrosis factorα(TNF-α),interleukin 1β(IL-1β),and IL-18 in colon tissue,and significantly increase the expression of the anti-inflammatory factor IL-10.In conclusion,these results demonstrated that BCFAs in goat milk exerted effects on colitis-related inflammatory cytokines and inhibited inflammation by inducing the TLR4/NF-κB/NLRP3 pathway to alleviate DSS-induced ulcerative colitis.This study provides evidence for the potential of BCFAs as bioactive fatty acids in food products and to ameliorate ulcerative colitis development in mice. 展开更多
关键词 Goat milk Ulcerative colitis Branch-chain fatty acids TLR4/NF-κB/nlrp3 pathway
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AMPK信号通路和NLRP3炎症小体在肝衰竭中的研究进展 被引量:1
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作者 陈倩 张清奇 龚作炯 《肝脏》 2023年第2期244-246,共3页
肝衰竭是由多种因素导致的严重肝脏结构和功能损伤,且是一个涉及“三重打击”的复杂病理生理过程。在机体内,AMPK信号在调节细胞能量平衡中起着重要作用。肝脏作为机体的代谢工厂,对能量的产生和利用有着严格的调控。此外,NLRP3炎症小... 肝衰竭是由多种因素导致的严重肝脏结构和功能损伤,且是一个涉及“三重打击”的复杂病理生理过程。在机体内,AMPK信号在调节细胞能量平衡中起着重要作用。肝脏作为机体的代谢工厂,对能量的产生和利用有着严格的调控。此外,NLRP3炎症小体也在众多炎症性疾病发生发展过程中扮演着重要角色。而AMPK信号通路和NLRP3小体之间存在交互影响。本文就AMPK介导的多种信号通路、NLRP3炎症小体的激活效应及二者之间的相互作用在肝衰竭过程中的研究进展做一综述。 展开更多
关键词 肝衰竭 三重打击 ampk信号通路 nlrp3炎症小体
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Teneligliptin mitigates diabetic cardiomyopathy by inhibiting activation of the NLRP3 inflammasome 被引量:5
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作者 Gu-Lao Zhang Yuan Liu +4 位作者 Yan-Feng Liu Xian-Tao Huang Yu Tao Zhen-Huan Chen Heng-Li Lai 《World Journal of Diabetes》 SCIE 2024年第4期724-734,共11页
BACKGROUND Diabetic cardiomyopathy(DCM),which is a complication of diabetes,poses a great threat to public health.Recent studies have confirmed the role of NLRP3(NOD-like receptor protein 3)activation in DCM developme... BACKGROUND Diabetic cardiomyopathy(DCM),which is a complication of diabetes,poses a great threat to public health.Recent studies have confirmed the role of NLRP3(NOD-like receptor protein 3)activation in DCM development through the inflammatory response.Teneligliptin is an oral hypoglycemic dipeptidyl peptidase-IV inhibitor used to treat diabetes.Teneligliptin has recently been reported to have anti-inflammatory and protective effects on myocardial cells.AIM To examine the therapeutic effects of teneligliptin on DCM in diabetic mice.METHODS Streptozotocin was administered to induce diabetes in mice,followed by treatment with 30 mg/kg teneligliptin.RESULTS Marked increases in cardiomyocyte area and cardiac hypertrophy indicator heart weight/tibia length reductions in fractional shortening,ejection fraction,and heart rate;increases in creatine kinase-MB(CK-MB),aspartate transaminase(AST),and lactate dehydrogenase(LDH)levels;and upregulated NADPH oxidase 4 were observed in diabetic mice,all of which were significantly reversed by teneligliptin.Moreover,NLRP3 inflammasome activation and increased release of interleukin-1βin diabetic mice were inhibited by teneligliptin.Primary mouse cardiomyocytes were treated with high glucose(30 mmol/L)with or without teneligliptin(2.5 or 5μM)for 24 h.NLRP3 inflammasome activation.Increases in CKMB,AST,and LDH levels in glucose-stimulated cardiomyocytes were markedly inhibited by teneligliptin,and AMP(p-adenosine 5‘-monophosphate)-p-AMPK(activated protein kinase)levels were increased.Furthermore,the beneficial effects of teneligliptin on hyperglycaemia-induced cardiomyocytes were abolished by the AMPK signaling inhibitor compound C.CONCLUSION Overall,teneligliptin mitigated DCM by mitigating activation of the NLRP3 inflammasome. 展开更多
关键词 Diabetic cardiomyopathy Teneligliptin nlrp3 ampk INTERLEUKIN-1Β
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Lacticaseibacillus rhamnosus Fmb14 ameliorates hyperuricemia-induced hepatocyte pyroptosis via NLRP3 inflammasome cascade inhibition
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作者 Hongyuan Zhao Xiaoyu Chen +4 位作者 Li Zhang Fanqiang Meng Libang Zhou Zhaoxin Lu Yingjian Lu 《Food Science and Human Wellness》 SCIE CAS CSCD 2024年第4期2174-2186,共13页
Hyperuricemia is a high-risk factor for the development of gout and renal fibrosis,but the adverse effects of hyperuricemia on the liver have been seriously neglected.This research investigated the ameliorating effect... Hyperuricemia is a high-risk factor for the development of gout and renal fibrosis,but the adverse effects of hyperuricemia on the liver have been seriously neglected.This research investigated the ameliorating effect of Lacticaseibacillus rhamnosus Fmb14 on hyperuricemia induced liver dysfunction both in vitro and in vivo.Cell free extracts of high dose L.rhamnosus Fmb14 treatment reduced the death rate of HepG2 cell lines from 24.1%to 14.9%by inhibiting NLRP3 recruitment,which was mainly activated by reactive oxygen species release and mitochondrial membrane potential disorder.In purine dietary induced hyperuricemia(PDIH)mice model,liver oedema and pyroptosis were ameliorated after L.rhamnosus Fmb14 administration through downregulating the expression levels of NLRP3,caspase-1 and gasdermin-D from 1.61 to 0.86,3.15 to 1.01 and 5.63 to 2.02,respectively.L.rhamnosus Fmb14 administration restored mitochondrial inner membrane protein(MPV17)and connexin 43 from 2.83 and 0.73 to 0.80 and 0.98 respectively in PDIH mice,indicating that dysbiosis of mitochondrial membrane potential was restored in liver.Intriguingly,PDIH pyroptosis stimulates the process of apoptosis,which leads to severe leakage of hepatocytes,and both of pyroptosis and apoptosis were decreased after L.rhamnosus Fmb14 treatment.Therefore,L.rhamnosus Fmb14 is a promising biological resource to maintain homeostasis of the liver in hyperuricemia and the prevention of subsequent complications. 展开更多
关键词 Lacticaseibacillus rhamnosus Fmb14 HYPERURICEMIA PYROPTOSIS nlrp3 pathway
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Elaidic acid-induced intestinal barrier damage led to gut-liver axis derangement and triggered NLRP3 inflammasome in the liver of SD rats
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作者 Hui Liu Xuenan Li +5 位作者 Lu Li Yucai Li Haiyang Yan Yong Pang Wenliang Li Yuan Yuan 《Food Science and Human Wellness》 SCIE CSCD 2024年第3期1279-1291,共13页
Previous studies have shown that trans fatty acids(TFA) are associated with several chronic diseases,the gut microbiota is directly influenced by dietary components and linked to chronic diseases.Our research investig... Previous studies have shown that trans fatty acids(TFA) are associated with several chronic diseases,the gut microbiota is directly influenced by dietary components and linked to chronic diseases.Our research investigated the effects of elaidic acid(EA),a typical TFA,on the gut microbiota to understand the underlying mechanisms of TFA-related chronic diseases.16S rDNA gene sequencing on faecal samples from Sprague-Dawley rats were performed to explore the composition change of the gut microbiota by EA gavage for 4 weeks.The results showed that the intake of EA increased the abundance of well-documented harmful bacteria,such as Proteobacteria,Anaerotruncus,Oscillibacter and Desulfovibrionaceae.Plus,EA induced translocation of lipopolysaccharides(LPS) and the above pathogenic bacteria,disrupted the intestinal barrier,led to gut-liver axis derangement and TLR4 pathway activation in the liver.Overall,EA induced intestinal barrier damage and regulated TLR4-MyD88-NF-κB/MAPK pathways in the liver of SD rats,leading to the activation of NLRP3 inflammasome and inflammatory liver damage. 展开更多
关键词 Elaidic acid(EA) Gut microbiota Intestinal barrier Gut-liver axis TLR4-MyD88-NF-κB/MAPK pathways nlrp3 inflammasome
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To investigate the effect of Shenqi Tiaoshen Formula on CSE induced inflammatory response of MH-S cells based on TLR4/NF-kB/NLRP3 pathway
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作者 Wang Hui Yang Qin-jun +4 位作者 ZHOU Fan-chao Yang Cheng TONG Jia-bing LI Ze-geng 《Journal of Hainan Medical University》 CAS 2023年第17期15-20,共6页
Objective:To study the effects of Shenqi Tiaoshen Formula(SQTS)on the inflammatory response of MH-S cells induced by cigarette smoking extract(CSE)and its mechanism based on TLR4/NF-kB/NLRP3 pathway.Methods:MH-S cells... Objective:To study the effects of Shenqi Tiaoshen Formula(SQTS)on the inflammatory response of MH-S cells induced by cigarette smoking extract(CSE)and its mechanism based on TLR4/NF-kB/NLRP3 pathway.Methods:MH-S cells were used as subjects to evaluate cell viability by CCK-8 method.The levels of TNF-α,IL-1βand IL-6 in the supernatant were detected by ELISA.ROS were detected by DCFH-DA fluorescence probe.Western blotting was used to detect the expression of TLR4/NF-kB/NLRP3 pathway protein,and TAK-242,a TLR4 inhibitor,was used to verify the role of SQTS in the TLR4/NF-kB/NLRP3 pathway.Results:Compared with blank group,the cell survival rate of CSE group was decreased,and the contents of inflammatory cytokines TNF-α,IL-1βand IL-6 were increased(P<0.05),ROS fluorescence expression level was significantly increased(P<0.01),TLR4/NF-kB/NLRP3 pathway protein expression was significantly increased(P<0.05);Compared with CSE group,the survival rate of cells in SQTS groups was increased,and the expression levels of the above indexes were decreased(P<0.05),and TLR4/NF-kB/NLRP3 pathway protein decreased in TAK-242 groups(P<0.05).Conclusion:SQTS can reduce the inflammatory response of MH-S cells induced by CSE by inhibiting TLR4/NF-kB/NLRP3 pathway. 展开更多
关键词 Shenqi Tiaoshen Formula CSE MH-S cells TLR4/NF-kB/nlrp3 signaling pathway Inflammation
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Mechanism of Sanshi decoction inhibits macrophage pyroptosis by inhibiting BRD4/NF-κB/NLRP3 pathway in the treatment of gouty arthritis
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作者 PIAO Yong-zhu QI Ming-ming +3 位作者 NIE Shuang-lian PAN Guo-xiong ZHANG Hao WANG Xin-bo 《Journal of Hainan Medical University》 CAS 2023年第24期18-24,共7页
Objective:To observe the effect of Sanshi decoction on BRD4/NF-κB/NLRP3 pathwaymediated macrophage pyroptosis,so as to elucidate the molecular mechanism of Sanshi decoction in the treatment of gouty arthritis.Methods... Objective:To observe the effect of Sanshi decoction on BRD4/NF-κB/NLRP3 pathwaymediated macrophage pyroptosis,so as to elucidate the molecular mechanism of Sanshi decoction in the treatment of gouty arthritis.Methods:THP-1 was induced into macrophages with foboside and the divided into the control group,model group,low-dose,medium-dose,high-dose group of Sanshi decoction,and BRD4 inhibitor group.Except for the control group,the remaining groups were induced with monosodium urate crystals to construct a gouty arthritis cell model.The activity of macrophages was detected by CCK8,the level of macrophage pyroptosis was detected by flow cytometry,the activity of LDH,the content of IL-1β and IL-18 were detected by enzyme-linked immunosorbent assay,and the expression of related proteins in the BRD4/NF-κB/NLRP3 pathway was detected by Western blot.Results:Compared with the control group,macrophage activity was decreased in the model group,and the level of pyroptosis,LDH activity,contents of IL-1β and IL-18,expression levels of BRD4,p-NF-kB p65,NLRP3,Caspase-1 p20,and IL-1β protein were significantly up-regulated,the differences were statistically significant(P<0.05 and P<0.01).Compared with the model group,macrophage activity was up-regulated in the Sanshi Decoction,and the level of pyroptosis,LDH activity,IL-1β and IL-18 contents,expression levels of BRD4,p-NF-kB p65,NLRP3,Caspase-1 p20,and IL-1β protein were significantly decreased with statistically significant differences(P<0.05 and P<0.01).Conclusion:Sanshi decoction inhibits macrophage pyroptosis by inhibiting BRD4/NF-κB/NLRP3 pathway activation,thus improving the inflammation level of gouty arthritis. 展开更多
关键词 Gouty arthritis MACROPHAGE PYROPTOSIS BRD4/NF-κB/nlrp3 pathway Sanshi decoction
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Fisetin mitigates hepatic ischemia-reperfusion injury by regulating GSK3β/AMPK/NLRP3 inflammasome pathway 被引量:13
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作者 Jun-Liang Pu Zuo-Tian Huang +5 位作者 Yun-Hai Luo Tong Mou Ting-Ting Li Zhong-Tang Li Xu-Fu Wei Zhong-Jun Wu 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS CSCD 2021年第4期352-360,共9页
Background: Hepatic ischemia-reperfusion(I/R) injury(IRI) represents a crucial challenge in liver transplantation. Fisetin has anti-inflammatory, anti-aging and anti-oxidative properties. This study aimed to examine w... Background: Hepatic ischemia-reperfusion(I/R) injury(IRI) represents a crucial challenge in liver transplantation. Fisetin has anti-inflammatory, anti-aging and anti-oxidative properties. This study aimed to examine whether fisetin mitigates hepatic IRI and examine its underlying mechanisms. Methods: Sham or warm hepatic I/R operated mice were pretreated with fisetin(5, 10 or 20 mg/kg). Hepatic histological assessments, TUNEL assays and serum aminotransferase measurements were performed. An in vitro hypoxia/reoxygenation(H/R) model using RAW264.7 macrophages pretreated with fisetin(2.5, 5 or 10 μmol/L) was also used. Serum and cell supernatant concentrations of interleukin-1 β(IL-1 β), IL-18 and tumor necrosis factor-α(TNF-α) were determined by enzyme-linked immunosorbent assay(ELISA). Protein levels of p-GSK3 β, p-AMPK and NLR family pyrin domain-containing 3(NLRP3)-associated proteins were detected by Western blotting. Results: Compared with the I/R group, fisetin pretreatment reduced pathological liver damage, serum aminotransferase levels, serum concentrations of IL-1 β, IL-18 and TNF-α in the murine IRI model. Fisetin also reduced the expression of NLRP3 inflammasome-associated proteins(NLRP3, cleaved caspase-1, IL-1 β and IL-18) in I/R-operated liver. The experiments in vitro showed that fisetin decreased the release of IL-1 β, IL-18 and TNF-α, and reduced the expression of NLRP3 inflammasome-associated proteins in H/R-treated RAW264.7 cells. Moreover, fisetin increased the expressions of p-GSK3 β and p-AMPK in both models, indicating that its anti-inflammatory effects were dependent on GSK3 β/AMPK signaling. The antiinflammatory effects of fisetin were partially inhibited by the AMPK specific inhibitor compound C. Conclusions: Fisetin showed protective effects against hepatic IRI, countering inflammatory responses through mediating the GSK3 β/AMPK/NLRP3 inflammasome pathway. 展开更多
关键词 FISETIN Hepatic ischemia-reperfusion injury GSK3βampk nlrp3
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Acacetin protects against cerebral ischemia-reperfusion injury via the NLRP3 signaling pathway 被引量:26
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作者 Juan Bu Shen Shi +8 位作者 Hui-Qin Wang Xiao-Shan Niu Zong-Feng Zhao Wei-Dong Wu Xiao-Ling Zhang Zhi Ma Yan-Jun Zhang Hui Zhang Yi Zhu 《Neural Regeneration Research》 SCIE CAS CSCD 2019年第4期605-612,共8页
Acacetin(5,7-dihydroxy-4′-methoxyflavone), a potential neuroprotective agent, has an inhibitory effect on lipopolysaccharide-induced neuroinflammatory reactions. However, whether acacetin has an effect on inflammator... Acacetin(5,7-dihydroxy-4′-methoxyflavone), a potential neuroprotective agent, has an inhibitory effect on lipopolysaccharide-induced neuroinflammatory reactions. However, whether acacetin has an effect on inflammatory corpuscle 3(NLRP3) after cerebral ischemia-reperfusion injury has not been fully determined. This study used an improved suture method to establish a cerebral ischemia-reperfusion injury model in C57BL/6 mice. After ischemia with middle cerebral artery occlusion for 1 hour, reperfusion with intraperitoneal injection of 25 mg/kg of acacetin(acacetin group) or an equal volume of saline(0.1 mL/10 g, middle cerebral artery occlusion group) was used to investigate the effect of acacetin on cerebral ischemia-reperfusion injury. Infarct volume and neurological function scores were determined by 2,3,5-triphenyltetrazolium chloride staining and the Zea-Longa scoring method. Compared with the middle cerebral artery occlusion group, neurological function scores and cerebral infarction volumes were significantly reduced in the acacetin group. To understand the effect of acacetin on microglia-mediated inflammatory response after cerebral ischemia-reperfusion injury, immunohistochemistry for the microglia marker calcium adapter protein ionized calcium-binding adaptor molecule 1(Iba1) was examined in the hippocampus of ischemic brain tissue. In addition, tumor necrosis factor-α, interleukin-1β, and interleukin-6 expression in ischemic brain tissue of mice was quantified by enzyme-linked immunosorbent assay. Expression of Iba1, tumor necrosis factor-α, interleukin-1β and interleukin-6 was significantly lower in the acacetin group compared with the middle cerebral artery occlusion group. Western blot assay results showed that expression of Toll-like receptor 4, nuclear factor kappa B, NLRP3, procaspase-1, caspase-1, pro-interleukin-1β, and interleukin-1β were significantly lower in the acacetin group compared with the middle cerebral artery occlusion group. Our findings indicate that acacetin has a protective effect on cerebral ischemia-reperfusion injury, and its mechanism of action is associated with inhibition of microglia-mediated inflammation and the NLRP3 signaling pathway. 展开更多
关键词 nerve REGENERATION ACACETIN cerebral ISCHEMIA-REPERFUSION injury microglia nlrp3 inflammasome inflammatory FACTOR INFARCT volume signaling pathway nuclear factor-κB neuroprotection neural REGENERATION
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芝麻素通过AMPK/NLRP3信号通路缓解哮喘小鼠气道炎症的作用机制 被引量:4
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作者 朴琴姬 宋艺兰 +5 位作者 王知广 姜京植 朴艺花 李良昌 延光海 朴红梅 《免疫学杂志》 CAS CSCD 北大核心 2022年第6期487-494,共8页
目的探讨芝麻素通过AMPK/NLRP3信号通路缓解卵清蛋白(ovalbumin,OVA)诱导的哮喘小鼠模型的气道炎症。方法将40只雄性清洁级Balb/c小鼠,随机分为5组,分别为正常组(control)、OVA模型组、芝麻素低剂量组(50 mg/kg)、芝麻素高剂量组(100 mg... 目的探讨芝麻素通过AMPK/NLRP3信号通路缓解卵清蛋白(ovalbumin,OVA)诱导的哮喘小鼠模型的气道炎症。方法将40只雄性清洁级Balb/c小鼠,随机分为5组,分别为正常组(control)、OVA模型组、芝麻素低剂量组(50 mg/kg)、芝麻素高剂量组(100 mg/kg)、阳性对照地塞米松(dexamethasone,DEX)治疗组(1 mg/kg),每组8只。使用Diff-Quick染色法对每组小鼠肺泡灌洗液(BALF)中的各种炎症细胞进行分类、计数;小鼠BALF中IL-4、IL-5、IL-13、IFN-γ的含量使用ELISA法进行检测;流式细胞术测定小鼠肺组织CD4阳性细胞群中细胞因子的阳性百分率;对各组小鼠的肺组织进行HE、PAS染色,并观察其病理学改变;对小鼠肺组织进行免疫组织化学染色,观察NLRP3蛋白的表达分布情况;Western blot方法检测AMPK、p-AMPK、NLRP3、Caspase-1、ASC和IL-1β蛋白表达水平。结果芝麻素能够减少OVA引起的哮喘小鼠BALF中各种炎症细胞数量,降低小鼠BALF中IL-4、IL-5、IL-13的含量,提高IFN-γ的表达水平。通过芝麻素治疗后可抑制哮喘小鼠肺组织中炎性细胞浸润和气道上皮杯状细胞产生和黏液分泌,增加肺组织中p-AMPK的表达,降低NLRP3、Caspase-1、ASC和IL-1β蛋白表达,在哮喘小鼠肺组织中,Th2细胞因子IL-4水平降低,Th1细胞因子IFN-γ水平升高,恢复Th1/Th2平衡。结论芝麻素可以减轻哮喘小鼠气道炎症反应,其机制可能与AMPK/NLRP3信号通路有关。 展开更多
关键词 哮喘 芝麻素 气道炎症 ampk nlrp3
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Mechanism of Sanshi decoction in the treatment of gouty arthritis by NLRP3 inflammasome
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作者 PIAO Yong-zhu QI Ming-ming +3 位作者 NIE Shuang-lian PAN Guo-xiong ZHANG Hao WANG Xin-bo 《Journal of Hainan Medical University》 CAS 2023年第23期26-33,共8页
Objective:To observe the effect of Sanshi decoction on P2X7R/PKR pathway-mediated activation of macrophage NLRP3 inflammasome to elucidate the molecular mechanism of Sanshi decoction in the treatment of gouty arthriti... Objective:To observe the effect of Sanshi decoction on P2X7R/PKR pathway-mediated activation of macrophage NLRP3 inflammasome to elucidate the molecular mechanism of Sanshi decoction in the treatment of gouty arthritis.Methods:THP-1 macrophages were divided into control group,model group,low dose group,medium dose group,high dose group of Sanshi decoction and inhibitor group.The remaining groups were induced with monosodium urate crystals to establish a gouty arthritis cell model except the control group.Flow cytometry was used to detect macrophage ROS levels in each group,ELISA to detect MDA levels and SOD and GSH-PX activities in each group,and Western blot to detect P2X7R/PKR pathway and NLRP3 inflammasome-associated protein expression.We also used CCK-8 and flow cytometry to measure MH7A activity and apoptotic levels.Results:Compared with the control group,the ROS level,the content of MDA,the activities of SOD and GSH-PX were significantly increased,and the expression levels of NLRP3,full-length IL-1β,pro-IL-1β,full-length IL-18,pro-IL-18,full-length caspase-1,GSDMD-NT,P2X7R and p-PKR protein expression levels were significantly upregulated,and GSDMD-FL protein expression was significantly downregulated in the model group,and that the differences between them were statistically significant(P<0.05 and P<0.01).Compared with the model group,Sanshi decoction could reduce macrophage ROS levels,MDA content,SOD and GSHPX activities,and downregulate macrophage NLRP3,mature IL-1β,pro IL-1β,mature IL-18,pro IL-18,mature caspase-1,GSDMD-NT,P2X7R and p-PKR protein expression,and upregulate GSDMD-FL protein expression,with statistically significant differences(P<0.05 and P<0.01).In addition,MH7A activity was downregulated,and apoptosis level was upregulated in the model group in comparison with the control group,and differences were all significantly different(P<0.05).As compared to the model group,Sanshi decoction could significantly increase the activity of MH7A and inhibit the level of apoptosis,and that the differences between them were statistically significant(P<0.05 and P<0.01).Conclusion:Sanshi decoction can achieve the therapeutic effect of gouty arthritis by inhibiting P2X7R/PKR pathway activation,thus reducing the activation level of NLRP3. 展开更多
关键词 Gouty arthritis Sanshi decoction nlrp3 inflammasome P2X7R/PKR signaling pathway MACROPHAGES
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汉黄芩素调节AMPK/NLRP3信号通路对H/R诱导的心肌细胞凋亡的影响
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作者 李均 徐艺 +2 位作者 冉阳 徐刚 王均生 《现代生物医学进展》 CAS 2024年第17期3211-3216,3225,共7页
目的:探讨汉黄芩素(WOG)调节单磷酸腺苷活化蛋白激酶(AMPK)/NOD样受体蛋白3(NLRP3)信号通路对缺氧/再氧合(H/R)诱导的心肌细胞凋亡的影响。方法:将H9C2细胞分为Control组(正常培养)、H/R组(H/R诱导)、L(低剂量)-WOG组、M(中剂量)-WOG组... 目的:探讨汉黄芩素(WOG)调节单磷酸腺苷活化蛋白激酶(AMPK)/NOD样受体蛋白3(NLRP3)信号通路对缺氧/再氧合(H/R)诱导的心肌细胞凋亡的影响。方法:将H9C2细胞分为Control组(正常培养)、H/R组(H/R诱导)、L(低剂量)-WOG组、M(中剂量)-WOG组、H(高剂量)-WOG组(在H/R诱导的基础上分别加入40、80、120μmol/L的WOG)、WOG+Compound C组(在H-WOG组基础上加入10μmol/L AMPK抑制剂Compound C)。噻唑蓝(MTT)法和5-乙炔基-2′脱氧尿嘧啶核苷(EdU)染色检测WOG对H9C2细胞增殖的影响;流式细胞术检测WOG对H9C2细胞凋亡的影响;酶联免疫吸附试验(ELISA)检测H9C2细胞血清氧化应激指标[丙二醛(MDA)、活性氧类物质(ROS)、超氧化物歧化酶(SOD)]和炎症因子[白介素(IL)-1β、IL-18]水平;蛋白免疫印迹(WB)法检测H9C2细胞AMPK、NLRP3、B细胞淋巴瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)蛋白表达。结果:H/R组H9C2细胞的光密度值(OD490)、EdU阳性细胞率、SOD、AMPK、Bcl-2低于Control组,细胞凋亡率、IL-1β、IL-18、ROS、MDA、NLRP3、Bax高于Control组(P<0.05);与H/R组比较,L-WOG组、M-WOG组、H-WOG组OD_(490)、EdU阳性细胞率、SOD、AMPK、Bcl-2表达升高,细胞凋亡率、IL-1β、IL-18、ROS、MDA、NLRP3、Bax降低(P<0.05);WOG+Compound C组OD490、EdU阳性细胞率、SOD、AMPK、Bcl-2低于H-WOG组,细胞凋亡率、IL-1β、IL-18、ROS、MDA、NLRP3、Bax表达高于H-WOG组(P<0.05)。结论:WOG可以抑制H/R诱导的心肌细胞凋亡,其机制可能是通过介导AMPK/NLRP3信号通路有关。 展开更多
关键词 黄芩素 ampk/nlrp3信号通路 心肌细胞 细胞凋亡
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丹酚酸B调节SIRT1信号途径抑制H_(2)O_(2)诱导的NLRP3炎症小体激活 被引量:2
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作者 李庆菊 潘韵铮 +2 位作者 张琦 蒋宝平 许立 《中药新药与临床药理》 CAS CSCD 北大核心 2021年第5期604-611,共8页
目的基于沉默信息调节因子1(SIRT1)/NOD样受体蛋白3(NLRP3)炎症小体途径探讨丹酚酸B(Sal B)抗氧化应激致细胞损伤的作用机制,以期阐明丹酚酸B抗心肌缺血的作用机制。方法采用体外构建H_(2)O_(2)诱导的氧化应激细胞模型,将H9c2细胞分为6... 目的基于沉默信息调节因子1(SIRT1)/NOD样受体蛋白3(NLRP3)炎症小体途径探讨丹酚酸B(Sal B)抗氧化应激致细胞损伤的作用机制,以期阐明丹酚酸B抗心肌缺血的作用机制。方法采用体外构建H_(2)O_(2)诱导的氧化应激细胞模型,将H9c2细胞分为6组,分别为正常组、模型组(600μmol·L^(-1)H_(2)O_(2)刺激)、H_(2)O_(2)+丹酚酸B(5、10、20μmol·L^(-1))组和H_(2)O_(2)+丹酚酸B(20μmol·L^(-1))+EX527(10μmol·L^(-1))组。采用MTT法测定细胞活性;Hoechst染色法测定细胞凋亡;比色法及ELISA法分别测定乳酸脱氢酶(LDH)、白细胞介素(IL)-1β水平;采用DCFH-DA荧光探针检测细胞内活性氧(ROS)水平;采用JC-1荧光探针测定线粒体膜电位;Western Blot法测定H9c2细胞中NLRP3、半胱氨酸天冬氨酸蛋白酶1(Caspase-1)、凋亡相关斑点样蛋白(ASC),以及SIRT1信号通路相关的SIRT1、磷酸化AMP蛋白活化激酶α(p-AMPKα)、AMP蛋白活化激酶α(AMPKα)、过氧化物酶体增殖物激活受体γ共激活因子1α(PGC-1α)蛋白表达。结果与正常组比较,模型组细胞活力及线粒体膜电位明显降低(P<0.01),细胞凋亡程度及细胞内ROS、LDH和炎症因子IL-1β水平明显升高(P<0.01);与NLRP3炎症小体相关的NLRP3、Caspase-1和ASC蛋白表达显著上调(P<0.01),SIRT1、p-AMPKα/AMPKα和PGC-1α蛋白表达明显下调(P<0.01)。与模型组比较,丹酚酸B组的细胞活力以及线粒体膜电位显著升高(P<0.05,P<0.01),细胞凋亡程度及细胞内ROS、LDH及炎症因子IL-1β释放水平明显降低(P<0.01)。丹酚酸B能够明显上调SIRT1信号通路中SIRT1、p-AMPKα/AMPKα、PGC-1α蛋白表达(P<0.05,P<0.01),下调NLRP3炎症小体相关的NLRP3、Caspase-1和ASC蛋白表达(P<0.05,P<0.01),且呈一定量效关系。在应用SIRT1特异性抑制剂EX527干预后,丹酚酸B抑制H_(2)O_(2)诱导的NLRP3炎症小体激活作用被明显逆转。结论丹酚酸B可能通过激活SIRT1/AMPK/PGC-1α信号通路,抑制氧化应激诱导的NLRP3炎症小体的激活,继而发挥抗心肌缺血作用。 展开更多
关键词 丹酚酸B 氧化应激 心肌缺血 nlrp3炎症小体 SIRT1/ampk/PGC-1α信号通路 H9C2细胞
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Puerarin protects rat brain against ischemia/reperfusion injury by suppressing autophagy via the AMPK-mT OR-ULK1 signaling pathway 被引量:52
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作者 Jin-Feng Wang Zhi-Gang Mei +7 位作者 Yang Fu Song-Bai Yang Shi-Zhong Zhang Wei-Feng Huang Li Xiong Hua-Jun Zhou Wei Tao Zhi-Tao Feng 《Neural Regeneration Research》 SCIE CAS CSCD 2018年第6期989-998,共10页
Puerarin suppresses autophagy to alleviate cerebral ischemia/reperfusion injury, and accumulating evidence indicates that the AMPKm TOR signaling pathway regulates the activation of the autophagy pathway through the c... Puerarin suppresses autophagy to alleviate cerebral ischemia/reperfusion injury, and accumulating evidence indicates that the AMPKm TOR signaling pathway regulates the activation of the autophagy pathway through the coordinated phosphorylation of ULK1. In this study, we investigated the mechanisms underlying the neuroprotective effect of puerarin and its role in modulating autophagy via the AMPK-m TOR-ULK1 signaling pathway in the rat middle cerebral artery occlusion model of cerebral ischemia/reperfusion injury. Rats were intraperitoneally injected with puerarin, 50 or 100 mg/kg, daily for 7 days. Then, 30 minutes after the final administration, rats were subjected to transient middle cerebral artery occlusion for 90 minutes. Then, after 24 hours of reperfusion, the Longa score and infarct volume were evaluated in each group. Autophagosome formation was observed by transmission electron microscopy. LC3, Beclin-1 p62, AMPK, m TOR and ULK1 protein expression levels were examined by immunofluorescence and western blot assay. Puerarin substantially reduced the Longa score and infarct volume, and it lessened autophagosome formation in the hippocampal CA1 area following cerebral ischemia/reperfusion injury in a dose-dependent manner. Pretreatment with puerarin(50 or 100 mg/kg) reduced Beclin-1 expression and the LC3-II/LC3-I ratio, as well as p-AMPK and p S317-ULK1 levels. In comparison, it increased p62 expression. Furthermore, puerarin at 100 mg/kg dramatically increased the levels of p-m TOR and p S757-ULK1 in the hippocampus on the ischemic side. Our findings suggest that puerarin alleviates autophagy by activating the APMK-m TOR-ULK1 signaling pathway. Thus, puerarin might have therapeutic potential for treating cerebral ischemia/reperfusion injury. 展开更多
关键词 nerve regeneration PUERARIN AUTOPHAGY cerebral ischemia/reperfusion ampk-m TOR-ULK1 signaling pathway light chain 3 p62 ischemic stroke ampk/m TOR traditional Chinese medicine middle cerebral artery occlusion neural regeneration
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三七皂苷通过AMPK/DRP1介导的线粒体裂变减轻过敏性鼻炎 被引量:2
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作者 张雅琳 王重阳 +4 位作者 刘思奇 金海南 宋艺兰 延光海 金永德 《中国药理学通报》 CAS CSCD 北大核心 2023年第3期512-519,共8页
目的探讨三七皂苷(notoginsenoside R1,PNS-R1)是否通过AMP激活蛋白激酶(AMP-activated protein kinase,AMPK)/线粒体裂变关键蛋白(dynamin-related protein 1,DRP1)介导的线粒体裂变减轻过敏性鼻炎(allergic rhinitis,AR)。方法利用不... 目的探讨三七皂苷(notoginsenoside R1,PNS-R1)是否通过AMP激活蛋白激酶(AMP-activated protein kinase,AMPK)/线粒体裂变关键蛋白(dynamin-related protein 1,DRP1)介导的线粒体裂变减轻过敏性鼻炎(allergic rhinitis,AR)。方法利用不同剂量PNS-R1治疗卵清蛋白(Ovalbumin,OVA)诱导的AR小鼠,通过观察擦鼻、打喷嚏的过敏症状和鼻组织的HE染色探索PNS-R1在AR中的抑制作用。通过酶联免疫吸附法(ELISA)检测血清IgE水平和鼻灌洗液(nasal lavage fluid,NLF)炎性细胞因子水平,Western blot检测凋亡相关蛋白。在体外,利用IL-13刺激人鼻黏膜上皮细胞(human nasal epithelial cells,HNEpC),观察细胞凋亡、线粒体膜电位、细胞活性氧(reactive oxygen species,ROS)和线粒体ROS(mtROS)生成、AMPK/DRP1,TXNIP/NLRP3炎症小体的表达水平以及DRP1易位情况。结果PNS-R1减轻了AR小鼠的过敏症状,HE染色炎性细胞减少,降低血清OVA特异性IgE水平以及NLF中IL-4、IL-6和IL-8的水平。在体外,PNS-R1上调IL-13刺激后的线粒体膜电位,降低ROS和mtROS生成、减少cleaved-caspase-3、Bax和上调Bcl-2表达,以AMPK依赖性方式下调DRP1磷酸化(Ser 616)和DRP1在线粒体膜上的易位,减少TXNIP/NLRP3表达。结论PNS-R1通过抑制AMPK/DRP1信号轴及随后的TXNIP/NLRP3信号轴保护线粒体的完整性,缓解AR。 展开更多
关键词 AR模型 PNS-R1 ampk DRP1 TXNIP/nlrp3
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