BACKGROUND The NOD-like receptor family pyrin domain-containing 3(NLRP3)inflammasome is a significant component of the innate immune system that plays a vital role in the development of various parasitic diseases.Howe...BACKGROUND The NOD-like receptor family pyrin domain-containing 3(NLRP3)inflammasome is a significant component of the innate immune system that plays a vital role in the development of various parasitic diseases.However,its role in hepatic alveolar echinococcosis(HAE)remains unclear.AIM To investigate the NLRP3 inflammasome and its mechanism of activation in HAE.METHODS We assessed the expression of NLRP3,caspase-1,interleukin(IL)-1β,and IL-18 in the marginal zone and corresponding normal liver of 60 patients with HAE.A rat model of HAE was employed to investigate the role of the NLRP3 inflammasome in the marginal zone of HAE.Transwell experiments were conducted to investigate the effect of Echinococcus multilocularis(E.multilocularis)in stimulating Kupffer cells and hepatocytes.Furthermore,immunohistochemistry,Western blotting,and enzyme-linked immunosorbent assay were used to evaluate NLRP3,caspase-1,IL-1β,and IL-18 expression;flow cytometry was used to detect apoptosis and reactive oxygen species(ROS).RESULTS NLRP3 inflammasome activation was significantly associated with ROS.Inhibition of ROS production decreased NLRP3-caspase-1-IL-1βpathway activation and mitigated hepatocyte damage and inflammation.CONCLUSION E.multilocularis induces hepatocyte damage and inflammation by activating the ROS-mediated NLRP3-caspase-1-IL-1βpathway in Kupffer cells,indicating that ROS may serve as a potential target for the treatment of HAE.展开更多
OBJECTIVE:To investigate the impact of Yemazhui(Herba Eupatorii Lindleyani,HEL)against lipopolysaccharide(LPS)-induced acute lung injury(ALI)and explore its underlying mechanism in vivo.METHODS:The chemical constituen...OBJECTIVE:To investigate the impact of Yemazhui(Herba Eupatorii Lindleyani,HEL)against lipopolysaccharide(LPS)-induced acute lung injury(ALI)and explore its underlying mechanism in vivo.METHODS:The chemical constituents of HEL were analyzed by ultra-high performance liquid chromatographyquadrupole time-of-flight mass spectrometry method.Then,HEL was found to suppress LPS-induced ALI in vivo.Six-week-old male Sprague-Dawley rats were randomly divided into 6 groups:control,LPS,Dexamethasone(Dex),HEL low dose 6 g/kg(HEL-L),HEL medium dose 18 g/kg(HEL-M)and HEL high dose 54 g/kg(HEL-H)groups.The model rats were intratracheally injected with 3 mg/kg LPS to establish an ALI model.Leukocyte counts,lung wet/dry weight ratio,as well as myeloperoxidase(MPO)activity were determined followed by the detection with hematoxylin and eosin staining,enzyme linked immunosorbent assay,quantitative real time polymerase chain reaction,western blotting,immunohistochemistry,and immunofluorescence.Besides,to explore the effect of HEL on ALI-mediated intestinal flora,we performed 16s rRNA sequencing analysis of intestinal contents.RESULTS:HEL attenuated LPS-induced inflammation in lung tissue and intestinal flora disturbance.Mechanism study indicated that HEL suppressed the lung coefficient and wet/dry weight ratio of LPS-induced ALI in rats,inhibited leukocytes exudation and MPO activity,and improved the pathological injury of lung tissue.In addition,HEL reduced the expression of tumor necrosis factoralpha,interleukin-1beta(IL-1β)and interleukin-6(IL-6)in bronchoalveolar lavage fluid and serum,and inhibited nuclear displacement of nuclear factor kappa-B p65(NF-κBp65).And 18 g/kg HEL also reduced the expression levels of toll-like receptor 4(TLR4),myeloid differentiation factor 88,NF-κBp65,phosphorylated inhibitor kappa B alpha(phospho-IκBα),nod-like receptor family pyrin domain-containing 3 protein(NLRP3),IL-1β,and interleukin-18(IL-18)in lung tissue,and regulated intestinal flora disturbance.CONCLUSIONS:In summary,our findings revealed that HEL has a protective effect on LPS-induced ALI in rats,and its mechanism may be related to inhibiting TLR4/NF-κB/NLRP3 signaling pathway and improving intestinal flora disturbance.展开更多
OBJECTIVE:To investigate the efficacy of Qingchi San(青赤散,QCS),a preparation of Traditional Chinese Medicine,on ulcerative colitis(UC)in mice by inhibiting the nuclearfactor-kappa B(NF-κB)signaling pathway and nucl...OBJECTIVE:To investigate the efficacy of Qingchi San(青赤散,QCS),a preparation of Traditional Chinese Medicine,on ulcerative colitis(UC)in mice by inhibiting the nuclearfactor-kappa B(NF-κB)signaling pathway and nucleotide-binding oligomerization domain,leucine-rich repeat and pyrin domain-containing 3(NLRP3)inflammasome formation.METHODS:The UC model was established with male C57BL/6J as the animal model.Bodyweight,Disease Activity Index(DAI),colon length and weight were detected.Furthermore,colonic histology was performed by hematoxylin-eosin(HE)staining.interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),myeloperoxidase(MPO)and superoxide dismutase(SOD)were performed by enzyme-linked immunosorbent assay.Cyclooxygenase 2(COX2)and inducible nitric oxide synthase(iNOS)mRNA expression were conducted by real-time quantitative polymerase chain reaction(RT-qPCR).NF-κB,inhibitor of NF-κBα(iκBα),Phosphorylated inhibitor of NF-κBα(p-iκBα),caspase-1,NLRP3 and Apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC)protein expression were conducted by Western blotting.RESULTS:Compared with UC model group,Bodyweight was significantly increased in QCS treatment.At the same time,DAI was significantly decreased in QCS treatment.Colon length and weight and colonic histology were significantly improved in QCS treatment.Furthermore,the expression of IL-1β,IL-6,TNF-α,MPO,SOD,COX2,and iN OS were significantly decreased in QCS treatment.Finally,the expression of NF-κB signaling pathway-related proteins NF-κB,iκBα,p-iκBα,and the expression of NLRP3 inflammasome related proteins caspase-1,NLRP3 and ASC were significantly decreased in QCS treatment.CONCLUSION:Traditional Chinese drug QCS could treat UC by inhibiting the NF-κB signaling pathway and NLRP3 inflammasome formation in mice.展开更多
OBJECTIVE:To investigate the effects of Qingre Jianpi decoction(清热健脾汤,QRJPD)on dextran sulfate sodium(DSS)-induced colitis mice and explore its mechanism.METHODS:All mice were randomly divided into six groups.Wei...OBJECTIVE:To investigate the effects of Qingre Jianpi decoction(清热健脾汤,QRJPD)on dextran sulfate sodium(DSS)-induced colitis mice and explore its mechanism.METHODS:All mice were randomly divided into six groups.Weight changes,disease activity index values,and histological damage were detected.Inflammatory cytokines and immune cell infiltration were measured using enzyme-linked immunosorbent assays(ELISA)and immunohistochemistry(IHC)method.The key protein expression levels of the NOD-like receptor family pyrin domain-containing 3(NLRP3)inflammasome were detected by western blot analysis,IHC,and quantitative reverse transcription polymerase chain reaction.RESULTS:QRJPD played an anti-inflammatory role in the treatment of ulcerative colitis(UC),reduced the secretion of inflammatory cytokines,and inhibited the inflammatory infiltration of immune cells by suppressing DSS-induced activation of the NLRP3 inflammasome.CONCLUSION:QRJPD exerts protective effects by inhibiting DSS-induced NLRP3 inflammasome activation.展开更多
Noise-induced hearing loss is the primary non-genetic factor contributing to auditory dysfunction.However,there are currently no effective pharmacological interventions for patients with noise-induced hearing loss.Her...Noise-induced hearing loss is the primary non-genetic factor contributing to auditory dysfunction.However,there are currently no effective pharmacological interventions for patients with noise-induced hearing loss.Here,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory mechanisms.We established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 hours.We found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with tranylcypromine.The noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with saline.These findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell loss.Additionally,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy pathway.Tranylcypromine treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)production.In conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing function.These findings suggest that inhibiting lysine-specific demethylase 1 is a potential therapeutic strategy for preventing hair cell loss and noise-induced hearing loss.展开更多
目的研究术前NLR家族Pyrin域蛋白3(NLR family pyrin domain-containing protein 3,NLRP3)、白细胞介素(Interleukin,ILs)表达谱特征对神经胶质瘤患者手术预后的影响。方法以2019年1月-2022年12月新疆医科大学第二附属医院神经外科收治...目的研究术前NLR家族Pyrin域蛋白3(NLR family pyrin domain-containing protein 3,NLRP3)、白细胞介素(Interleukin,ILs)表达谱特征对神经胶质瘤患者手术预后的影响。方法以2019年1月-2022年12月新疆医科大学第二附属医院神经外科收治的86例神经胶质瘤患者为研究对象,根据患者术后1年内随访情况将患者划分为手术预后良好组(n=52)和手术预后不良组(n=34)。对比两组患者一般临床资料及术前NLRP3、ILs(IL-1β、IL-4、IL-12、IL-17、IL-33)表达谱的表达水平差异。采用Spearman相关性分析,经单因素及多因素Logistic回归分析筛选神经胶质瘤患者手术预后不良的危险因素,通过受试者工作特征(Receiver operating characteristic,ROC)曲线评价各危险因素对患者手术预后的影响。结果与手术预后良好组比较,手术预后不良组患者肿瘤大小、肿瘤周围水肿患者比例、合并癫痫发作史患者比例、血清NLRP3、IL-1β、IL-4、IL-33水平均升高,术前卡氏功能状态评分、血清IL-12水平均降低,差异有统计学意义(P<0.05);Spearman相关性分析结果表明,肿瘤大小、肿瘤周围水肿、有癫痫发作史、血清中NLRP3、IL-1β、IL-4、IL-33水平均与手术预后不良呈正相关性,卡氏功能状态评分、IL-12与手术预后不良呈负相关性(P<0.05);单因素及多因素Logistic回归分析表明血清中NLRP3、IL-1β、IL-4水平均是神经胶质瘤患者手术预后不良的重要危险因素,IL-12是神经胶质瘤患者手术预后不良的重要保护因素(P<0.05);ROC曲线分析表明NLRP3、IL-1β、IL-4、IL-12独立及联合对于神经胶质瘤患者手术预后不良均具有较高预测效能(P<0.05)。结论神经胶质瘤患者NLRP3、ILs水平较高均是手术预后不良的重要危险因素,通过早期干预减轻神经胶质瘤患者炎症水平可能有利于改善手术治疗效果。展开更多
Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic ...Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3(NLRP3) inflammasome. 3′-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3′-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3′-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3′-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3′-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3′-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3′-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3′-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.展开更多
基金Supported by the National Major Research and Development Project of“Precision Medicine Research”,No.2017YFC0909900Qinghai Province Science and Technology Department Programme,No.2019-SF-131the Qinghai Province Health and Family Planning Commission Programme,No.2016-wjzd-04.
文摘BACKGROUND The NOD-like receptor family pyrin domain-containing 3(NLRP3)inflammasome is a significant component of the innate immune system that plays a vital role in the development of various parasitic diseases.However,its role in hepatic alveolar echinococcosis(HAE)remains unclear.AIM To investigate the NLRP3 inflammasome and its mechanism of activation in HAE.METHODS We assessed the expression of NLRP3,caspase-1,interleukin(IL)-1β,and IL-18 in the marginal zone and corresponding normal liver of 60 patients with HAE.A rat model of HAE was employed to investigate the role of the NLRP3 inflammasome in the marginal zone of HAE.Transwell experiments were conducted to investigate the effect of Echinococcus multilocularis(E.multilocularis)in stimulating Kupffer cells and hepatocytes.Furthermore,immunohistochemistry,Western blotting,and enzyme-linked immunosorbent assay were used to evaluate NLRP3,caspase-1,IL-1β,and IL-18 expression;flow cytometry was used to detect apoptosis and reactive oxygen species(ROS).RESULTS NLRP3 inflammasome activation was significantly associated with ROS.Inhibition of ROS production decreased NLRP3-caspase-1-IL-1βpathway activation and mitigated hepatocyte damage and inflammation.CONCLUSION E.multilocularis induces hepatocyte damage and inflammation by activating the ROS-mediated NLRP3-caspase-1-IL-1βpathway in Kupffer cells,indicating that ROS may serve as a potential target for the treatment of HAE.
基金Natural Science Foundation Project of Chongqing Municipality:a Metabolome-based Study on the Protective Mechanism of Yemazhui(Herba Eupatorii Lindleyani)Sesquiterpene Lactones Against Acute Lung Injury(No.cstc2021jcyj-msxmX0365)Science and Technology Research Program of Chongqing Municipal Education Commission:a Cytokine Storm-based Study of the Protective Effect of Yemazhui(Herba Eupatorii Lindleyani)Extract Intervention on COVID-19 Lung Injury(No.KJZD-K202215101)。
文摘OBJECTIVE:To investigate the impact of Yemazhui(Herba Eupatorii Lindleyani,HEL)against lipopolysaccharide(LPS)-induced acute lung injury(ALI)and explore its underlying mechanism in vivo.METHODS:The chemical constituents of HEL were analyzed by ultra-high performance liquid chromatographyquadrupole time-of-flight mass spectrometry method.Then,HEL was found to suppress LPS-induced ALI in vivo.Six-week-old male Sprague-Dawley rats were randomly divided into 6 groups:control,LPS,Dexamethasone(Dex),HEL low dose 6 g/kg(HEL-L),HEL medium dose 18 g/kg(HEL-M)and HEL high dose 54 g/kg(HEL-H)groups.The model rats were intratracheally injected with 3 mg/kg LPS to establish an ALI model.Leukocyte counts,lung wet/dry weight ratio,as well as myeloperoxidase(MPO)activity were determined followed by the detection with hematoxylin and eosin staining,enzyme linked immunosorbent assay,quantitative real time polymerase chain reaction,western blotting,immunohistochemistry,and immunofluorescence.Besides,to explore the effect of HEL on ALI-mediated intestinal flora,we performed 16s rRNA sequencing analysis of intestinal contents.RESULTS:HEL attenuated LPS-induced inflammation in lung tissue and intestinal flora disturbance.Mechanism study indicated that HEL suppressed the lung coefficient and wet/dry weight ratio of LPS-induced ALI in rats,inhibited leukocytes exudation and MPO activity,and improved the pathological injury of lung tissue.In addition,HEL reduced the expression of tumor necrosis factoralpha,interleukin-1beta(IL-1β)and interleukin-6(IL-6)in bronchoalveolar lavage fluid and serum,and inhibited nuclear displacement of nuclear factor kappa-B p65(NF-κBp65).And 18 g/kg HEL also reduced the expression levels of toll-like receptor 4(TLR4),myeloid differentiation factor 88,NF-κBp65,phosphorylated inhibitor kappa B alpha(phospho-IκBα),nod-like receptor family pyrin domain-containing 3 protein(NLRP3),IL-1β,and interleukin-18(IL-18)in lung tissue,and regulated intestinal flora disturbance.CONCLUSIONS:In summary,our findings revealed that HEL has a protective effect on LPS-induced ALI in rats,and its mechanism may be related to inhibiting TLR4/NF-κB/NLRP3 signaling pathway and improving intestinal flora disturbance.
基金Supported by the National Key Research and Development Program(Grant 2018YFC1705403):Clinical Effect Evaluation of Chinese Medicine on Moderately Active Ulcerative ColitisNatural Science Foundation of Tianjin(Grant18JCYBJC26000):Study on the Mechanism of Qingchi San Treating Ulcerative Colitis By Regulating Gut Microflora+1 种基金Scientific Research Program of Tianjin Education Commission(Grant 2017KJ155):based onγδT-NLRP3 Inflammasome-Caspase PathwayQingchi San Regulates Gut Microflora to Treat UC。
文摘OBJECTIVE:To investigate the efficacy of Qingchi San(青赤散,QCS),a preparation of Traditional Chinese Medicine,on ulcerative colitis(UC)in mice by inhibiting the nuclearfactor-kappa B(NF-κB)signaling pathway and nucleotide-binding oligomerization domain,leucine-rich repeat and pyrin domain-containing 3(NLRP3)inflammasome formation.METHODS:The UC model was established with male C57BL/6J as the animal model.Bodyweight,Disease Activity Index(DAI),colon length and weight were detected.Furthermore,colonic histology was performed by hematoxylin-eosin(HE)staining.interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),myeloperoxidase(MPO)and superoxide dismutase(SOD)were performed by enzyme-linked immunosorbent assay.Cyclooxygenase 2(COX2)and inducible nitric oxide synthase(iNOS)mRNA expression were conducted by real-time quantitative polymerase chain reaction(RT-qPCR).NF-κB,inhibitor of NF-κBα(iκBα),Phosphorylated inhibitor of NF-κBα(p-iκBα),caspase-1,NLRP3 and Apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC)protein expression were conducted by Western blotting.RESULTS:Compared with UC model group,Bodyweight was significantly increased in QCS treatment.At the same time,DAI was significantly decreased in QCS treatment.Colon length and weight and colonic histology were significantly improved in QCS treatment.Furthermore,the expression of IL-1β,IL-6,TNF-α,MPO,SOD,COX2,and iN OS were significantly decreased in QCS treatment.Finally,the expression of NF-κB signaling pathway-related proteins NF-κB,iκBα,p-iκBα,and the expression of NLRP3 inflammasome related proteins caspase-1,NLRP3 and ASC were significantly decreased in QCS treatment.CONCLUSION:Traditional Chinese drug QCS could treat UC by inhibiting the NF-κB signaling pathway and NLRP3 inflammasome formation in mice.
基金Supported by National Science Foundation program of China(Activation of colonic mucosal mast cells and ion transport associated with serotonin receptors in the study of the role of soothing the liver and strengthening the spleen in the treatment of diarrheal irritable bowel syndrome,No.81473644)。
文摘OBJECTIVE:To investigate the effects of Qingre Jianpi decoction(清热健脾汤,QRJPD)on dextran sulfate sodium(DSS)-induced colitis mice and explore its mechanism.METHODS:All mice were randomly divided into six groups.Weight changes,disease activity index values,and histological damage were detected.Inflammatory cytokines and immune cell infiltration were measured using enzyme-linked immunosorbent assays(ELISA)and immunohistochemistry(IHC)method.The key protein expression levels of the NOD-like receptor family pyrin domain-containing 3(NLRP3)inflammasome were detected by western blot analysis,IHC,and quantitative reverse transcription polymerase chain reaction.RESULTS:QRJPD played an anti-inflammatory role in the treatment of ulcerative colitis(UC),reduced the secretion of inflammatory cytokines,and inhibited the inflammatory infiltration of immune cells by suppressing DSS-induced activation of the NLRP3 inflammasome.CONCLUSION:QRJPD exerts protective effects by inhibiting DSS-induced NLRP3 inflammasome activation.
基金supported by the National Key Research and Development Program of China,No.2022YFC2402701(to WC)Key International(Regional)Joint Research Program of the National Natural Science Foundation of China,No.81820108009(to SY)+5 种基金the National Natural Science Foundation of China,Nos.81970890(to WC)and 82371148(to WG)Fujian Provincial Healthcare Young and Middle-aged Backbone Talent Training Project,No.2023GGA035(to XC)Spring City Planthe High-level Talent Promotion and Training Project of Kunming,No.2022SCP001(to SY)the Natural Science Foundation of Hainan Province of China,No.824MS052(to XS)the Sixth Medical Center of Chinese PLA General Hospital Innovation Cultivation,No.CXPY202116(to LX)。
文摘Noise-induced hearing loss is the primary non-genetic factor contributing to auditory dysfunction.However,there are currently no effective pharmacological interventions for patients with noise-induced hearing loss.Here,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory mechanisms.We established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 hours.We found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with tranylcypromine.The noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with saline.These findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell loss.Additionally,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy pathway.Tranylcypromine treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)production.In conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing function.These findings suggest that inhibiting lysine-specific demethylase 1 is a potential therapeutic strategy for preventing hair cell loss and noise-induced hearing loss.
文摘目的研究术前NLR家族Pyrin域蛋白3(NLR family pyrin domain-containing protein 3,NLRP3)、白细胞介素(Interleukin,ILs)表达谱特征对神经胶质瘤患者手术预后的影响。方法以2019年1月-2022年12月新疆医科大学第二附属医院神经外科收治的86例神经胶质瘤患者为研究对象,根据患者术后1年内随访情况将患者划分为手术预后良好组(n=52)和手术预后不良组(n=34)。对比两组患者一般临床资料及术前NLRP3、ILs(IL-1β、IL-4、IL-12、IL-17、IL-33)表达谱的表达水平差异。采用Spearman相关性分析,经单因素及多因素Logistic回归分析筛选神经胶质瘤患者手术预后不良的危险因素,通过受试者工作特征(Receiver operating characteristic,ROC)曲线评价各危险因素对患者手术预后的影响。结果与手术预后良好组比较,手术预后不良组患者肿瘤大小、肿瘤周围水肿患者比例、合并癫痫发作史患者比例、血清NLRP3、IL-1β、IL-4、IL-33水平均升高,术前卡氏功能状态评分、血清IL-12水平均降低,差异有统计学意义(P<0.05);Spearman相关性分析结果表明,肿瘤大小、肿瘤周围水肿、有癫痫发作史、血清中NLRP3、IL-1β、IL-4、IL-33水平均与手术预后不良呈正相关性,卡氏功能状态评分、IL-12与手术预后不良呈负相关性(P<0.05);单因素及多因素Logistic回归分析表明血清中NLRP3、IL-1β、IL-4水平均是神经胶质瘤患者手术预后不良的重要危险因素,IL-12是神经胶质瘤患者手术预后不良的重要保护因素(P<0.05);ROC曲线分析表明NLRP3、IL-1β、IL-4、IL-12独立及联合对于神经胶质瘤患者手术预后不良均具有较高预测效能(P<0.05)。结论神经胶质瘤患者NLRP3、ILs水平较高均是手术预后不良的重要危险因素,通过早期干预减轻神经胶质瘤患者炎症水平可能有利于改善手术治疗效果。
基金supported by the National Natural Science Foundation of China,No.81971246 (to TM)Opening Foundation of Jiangsu Key Laboratory of Neurodegeneration,Nanjing Medical University,No.KF202204 (to LZ and SF)。
文摘Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3(NLRP3) inflammasome. 3′-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3′-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3′-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3′-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3′-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3′-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3′-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3′-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.
