重庆医科大学附属第一医院重症医学科,重庆 400016
Received:03 March 2024,
Revised:2024-03-20,
Accepted:21 March 2024,
Published:28 April 2024
移动端阅览
彭乔治,徐昉,林时辉.颗粒蛋白前体对脓毒症急性肺损伤小鼠肺组织核转录因子-κB的表达的影响[J].重庆医科大学学报,2024,49(4):395-400.
Peng Qiaozhi,Xu Fang,Lin Shihui.Effect of progranulin on the expression of nuclear factor-kappa B in lung tissue of mice with acute lung injury[J].Journal of Chongqing Medical University,2024,49(4):395-400.
彭乔治,徐昉,林时辉.颗粒蛋白前体对脓毒症急性肺损伤小鼠肺组织核转录因子-κB的表达的影响[J].重庆医科大学学报,2024,49(4):395-400. DOI: 10.13406/j.cnki.cyxb.003481.
Peng Qiaozhi,Xu Fang,Lin Shihui.Effect of progranulin on the expression of nuclear factor-kappa B in lung tissue of mice with acute lung injury[J].Journal of Chongqing Medical University,2024,49(4):395-400. DOI: 10.13406/j.cnki.cyxb.003481.
目的
2
探讨颗粒蛋白前体(progranulin,PGRN)对脓毒症急性肺损伤(acute lung injury,ALI)的影响及可能机制。
方法
2
将C57BL/6小鼠随机分为对照组(Control组)、急性肺损伤组(CLP组)、颗粒蛋白前体治疗组(CLP+PGRN组)。采用盲肠结扎穿刺术(cecal ligation and puncture,CLP)构建小鼠脓毒症ALI模型,CLP+PGRN组在CLP处理半小时后使用PGRN腹腔注射。24 h后麻醉并处死小鼠,取小鼠肺HE染色观察肺组织病理损伤;TUNEL法检测肺部细胞凋亡情况;免疫荧光染色检测肺组织中核转录因子-κB(nuclear factor kappa B,NF-κB)水平;Western blot法检测NF-κB、总p65和磷酸化p65表达水平;RT-qPCR检测NF-κB和炎症细胞因子水平。
结果
2
和Control组相比,CLP组和CLP+PGRN组肺损伤加重,促炎细胞因子升高,肺组织中细胞凋亡增加,NF-κB、p65和p-p65的表达水平明显增加;与CLP组相比,CLP+PGRN组肺组织损伤和凋亡减轻,促炎细胞因子降低,抑炎细胞因子升高,NF-κB、p65和p-p65的表达明显减少。
结论
2
PGRN可以减轻脓毒症小鼠急性肺损伤,其机制可能与抑制NF-κB、p65表达和p65磷酸化有关。
Objective
2
To investigate the effect and possible mechanisms of progranulin(PGRN) on acute lung injury(ALI) in sepsis.
Methods
2
C57BL/6 mice were randomly divided into normal control group(Control group),acute lung injury group(CLP group),and PGRN treatment group(CLP+PGRN group). Cecal ligation and puncture(CLP) was used to establish a mouse model of septic ALI,and the mice in the CLP+PGRN group were given intraperitoneal injection of PGRN at half an hour after CLP treatment. The mice were anesthetized and sacrificed after 24 hours,and lung tissue was collected for HE staining to observe the pathological damage of lungs; the TUNEL method was used to observe cell apoptosis in lungs;immunofluorescent staining was used to measure the level of nuclear factor-kappa B(NF-κB) in lung tissue;Western blot was used to measure the expression levels of NF-κB,total p65,and phosphorylated p65(p-p65),and RT-qPCR was used to measure the levels of NF-κB and inflammatory factors.
Results
2
Compared with the Control group,the CLP group and the CLP+PGRN group had aggravated lung injury and significant increases in proinflammatory cytokines,cell apoptosis in lung tissue,and the expression levels of NF-κB,p65,and p-p65. Compared with the CLP group,the CLP+PGRN group had alleviation of lung injury and apoptosis,a reduction in proinflammatory cytokines,increases in anti-inflammatory cytokines,and significant reductions in the expression levels of NF-κB,p65,and p-p65.
Conclusion
2
PGRN can alleviate ALI in mice with sepsis,possibly by inhibiting the expression of NF-κB and p65 and the phosphorylation of p65.
Villar J , Szakmany T , Grasselli G , et al . Redefining ARDS:a paradigm shift [J ] . Crit Care , 2023 , 27 ( 1 ): 416 .
Schmidt M , Hajage D , Lebreton G , et al . Prone positioning during extracorporeal membrane oxygenation in patients with severe ARDS:the PRONECMO randomized clinical trial [J ] . JAMA . 2023 ; 330 ( 24 ): 2343 - 2353 .
Attaway AH , Scheraga RG , Bhimraj A , et al . Severe covid-19 pneumonia:pathogenesis and clinical management [J ] . BMJ , 2021 , 372 : n436 .
Wilson JG , Calfee CS . ARDS subphenotypes:understanding a heterogeneous syndrome [J ] . Crit Care , 2020 , 24 ( 1 ): 102 .
Saeedi-Boroujeni A , Purrahman D , Shojaeian A , et al . Progranulin (PGRN) as a regulator of inflammation and a critical factor in the immunopathogenesis of cardiovascular diseases [J ] . J Inflamm , 2023 , 20 ( 1 ): 1 .
Xie W , Lu QC , Wang KL , et al . miR-34b-5p inhibition attenuates lung inflammation and apoptosis in an LPS-induced acute lung injury mouse model by targeting progranulin [J ] . J Cell Physiol , 2018 , 233 ( 9 ): 6615 - 6631 .
Mitchell S , Vargas J , Hoffmann A . Signaling via the NFκB system [J ] . Wiley Interdiscip Rev Syst Biol Med , 2016 , 8 ( 3 ): 227 - 241 .
Min Y , Kim MJ , Lee SN , et al . Inhibition of TRAF6 ubiquitin-ligase activity by PRDX1 leads to inhibition of NFKB activation and autophagy activation [J ] . Autophagy , 2018 , 14 ( 8 ): 1347 - 1358 .
Mikawa K , Nishina K , Takao Y , et al . ONO-1714,a nitric oxide synthase inhibitor,attenuates endotoxin-induced acute lung injury in rabbits [J ] . Anesth Analg , 2003 , 97 ( 6 ): 1751 - 1755 .
Luyt CE , Bouadma L , Morris AC , et al . Pulmonary infections complicating ARDS [J ] . Intensive Care Med , 2020 , 46 ( 12 ): 2168 - 2183 .
Asselah T , Durantel D , Pasmant E , et al . COVID-19:discovery,diagnostics and drug development [J ] . J Hepatol , 2021 , 74 ( 1 ): 168 - 184 .
Meyer NJ , Gattinoni L , Calfee CS . Acute respiratory distress syndrome [J ] . Lancet , 2021 , 398 ( 10300 ): 622 - 637 .
Lin SH , Wu H , Wang CJ , et al . Regulatory T cells and acute lung injury:cytokines,uncontrolled inflammation,and therapeutic implications [J ] . Front Immunol , 2018 , 9 : 1545 .
Huang GW , Jian JL , Liu CJ . Progranulinopathy:a diverse realm of disorders linked to progranulin imbalances [J ] . Cytokine Growth Factor Rev , 2023 : S1359-S6101(23)00078 - 3 .
Purrahman D , Shojaeian A , Poniatowski ŁA , et al . The role of progranulin (PGRN) in the pathogenesis of ischemic stroke [J ] . Cell Mol Neurobiol , 2023 , 43 ( 7 ): 3435 - 3447 .
Logan T , Simon MJ , Rana A , et al . Rescue of a lysosomal storage disorder caused by Grn loss of function with a brain penetrant progranulin biologic [J ] . Cell , 2024 , 187 ( 6 ): 1565 - 1566 .
Liu LL , Guo HM , Song AM , et al . Progranulin inhibits LPS-induced macrophage M1 polarization via NF-кB and MAPK pathways [J ] . BMC Immunol , 2020 , 21 ( 1 ): 32 .
Sun RX , Wang D , Song YX , et al . Granulin as an important immune molecule involved in lamprey tissue repair and regeneration by promoting cell proliferation and migration [J ] . Cell Mol Biol Lett , 2022 , 27 ( 1 ): 64 .
Wei J , Hettinghouse A , Liu C . The role of progranulin in arthritis [J ] . Ann N Y Acad Sci , 2016 , 1383 ( 1 ): 5 - 20 .
Boylan MA , Pincetic A , Romano G , et al . Targeting progranulin as an immuno-neurology therapeutic approach [J ] . Int J Mol Sci , 2023 , 24 ( 21 ): 15946 .
Yan D , Zhang YN , Huang YH , et al . Progranulin facilitates corneal repair through dual mechanisms of inflammation suppression and regeneration promotion [J ] . Inflammation , 2024 : 69 - 85 .
Purrahman D , Mahmoudian-Sani MR , Saki N , et al . Involvement of progranulin (PGRN) in the pathogenesis and prognosis of breast cancer [J ] . Cytokine , 2022 , 151 : 155803 .
Jian JL , Li GF , Hettinghouse A , et al . Progranulin:a key player in autoimmune diseases [J ] . Cytokine , 2018 , 101 : 48 - 55 .
Zhao MY , Wang MZ , Chen XX , et al . Targeting progranulin alleviated silica particles-induced pulmonary inflammation and fibrosis via decreasing Il-6 and Tgf-β1/Smad [J ] . J Hazard Mater , 2024 , 465 : 133199 .
Du H , Wong MY , Zhang TT , et al . A multifaceted role of progranulin in regulating amyloid-beta dynamics and responses [J ] . Life Sci Alliance , 2021 , 4 ( 7 ): e202000874 .
Chen SC , Bie MJ , Wang XW , et al . PGRN exacerbates the progression of non-small cell lung cancer via PI3K/AKT/Bcl-2 antiapoptotic signaling [J ] . Genes Dis , 2022 , 9 ( 6 ): 1650 - 1661 .
Efferth T , Oesch F . The immunosuppressive activity of artemisinin-type drugs towards inflammatory and autoimmune diseases [J ] . Med Res Rev , 2021 , 41 ( 6 ): 3023 - 3061 .
Barrat FJ , Crow MK , Ivashkiv LB . Interferon target-gene expression and epigenomic signatures in health and disease [J ] . Nat Immunol , 2019 , 20 ( 12 ): 1574 - 1583 .
L.J. Schlein , D.H. Thamm . NF-κB activation in canine cancer [J ] . Veterinary Pathology 59 (5) (2022) 724 - 732 .
Zusso M , Lunardi V , Franceschini D , et al . Ciprofloxacin and levofloxacin attenuate microglia inflammatory response via TLR4/NF-κB pathway [J ] . J Neuroinflammation , 2019 , 16 ( 1 ): 148 .
Wu YQ , Wang YH , Liu B , et al . SN50 attenuates alveolar hypercoagulation and fibrinolysis inhibition in acute respiratory distress syndrome mice through inhibiting NF-κB p65 translocation [J ] . Respir Res , 2020 , 21 ( 1 ): 130 .
Devi K , Soni S , Tripathi V , et al . Ethanolic Extract of Tridax procumbens mitigates pulmonary inflammation via inhibition of NF-κB/p65/ERK mediated signalling in an allergic asthma model [J ] . Phytomedicine , 022 , 99 : 154008 .
Cheng YM , Liu B , Qian H , et al . BAY11-7082 inhibits the expression of tissue factor and plasminogen activator inhibitor-1 in type-Ⅱ alveolar epithelial cells following TNF-α stimulation via the NF-κB pathway [J ] . Exp Ther Med , 2021 , 21 ( 2 ): 177 .
Zhou J , Peng ZL , Wang J . Trelagliptin alleviates lipopolysaccharide(LPS)-induced inflammation and oxidative stress in acute lung injury mice [J ] . Inflammation , 2021 , 44 ( 4 ): 1507 - 1517 .
Chen H , Zhang W , Luo S , et al . Lead exposure induces neuronal apoptosis via NFκB p65/RBBP4/Survivin signaling pathway [J ] . Toxicology , 2023 , 499 : 153654 .
0
Views
14
下载量
2
CSCD
Publicity Resources
Related Articles
Related Author
Related Institution
京公网安备11010802024621
