Glyburide attenuates ozone‐induced pulmonary inflammation and injury by blocking the NLRP3 inflammasome

Glyburide is a classic antidiabetic drug that is dominant in inflammation regulation, but its specific role in ozone‐induced lung inflammation and injury remains unclear. In order to investigate whether glyburide prevents ozone‐induced pulmonary inflammation and its mechanism, C57BL/6 mice were intratracheally pre‐instilled with glyburide or the vehicle 1 hour before ozone (1 ppm, 3 hours) or filtered air exposure. After 24 hours, the total inflammatory cells and total protein in bronchoalveolar lavage fluid (BALF) were detected. The pathological alternations in lung tissues were evaluated by HE staining. The expression of NLRP3, interleukin‐1β (IL‐1β), and IL‐18 protein in lung tissues was detected by immunohistochemistry. Western blotting was used to examine the levels of caspase‐1 p10 and active IL‐1β protein. Levels of IL‐1β and IL‐18 in BALF were measured using ELISA kits. Glyburide treatment decreased the total cells in BALF, the inflammatory score, and the mean linear intercept induced by ozone in lung tissues. In addition, glyburide inhibited the expression of NLRP3, IL‐18, and IL‐1β protein in lung tissues, and also suppressed NLRP3 inflammasome activation, including caspase‐1 p10, active IL‐1β protein in lung tissues, IL‐1β, and IL‐18 in BALF. These results demonstrate that glyburide effectively attenuates ozone‐induced pulmonary inflammation and injury via blocking the NLRP3 inflammasome.     

Dexamethasone alleviate allergic airway inflammation in mice by inhibiting the activation of NLRP3 inflammasome

Dexamethasone (DEX) is the mainstay treatment for asthma, which is a common chronic airway inflammation disease. However, the mechanism of DEX resolute symptoms of asthma is not completely clear. Here, we aimed to analyze the effect of DEX on airway inflammation in OVA-induced mice and whether this effect is related to the inhibition of the activation of NLRP3 inflammasome. Female (C57BL/6) mice were used to establish the allergic airway inflammation model by inhalation OVA. The number of inflammatory cells in the bronchi alveolar lavage fluid (BALF) was counted by Swiss-Giemsa staining, and the contents of IL-1β, IL-18, IL-5 and IL-17 were detected by ELISA. The degree of inflammatory cells infiltration and mucous cells proliferation in lung tissue were separately observed by H&E and PAS staining. The proteins expression of NLRP3, pro-caspase-1, caspase-1, IL-1β, IL-6 and IL-17 in lung tissue were detected by Western blotting. We found that DEX significantly inhibited OVA-induced inflammatory cells infiltration, airway mucus secretion and goblet cell proliferation in mice. The total and classified numbers of inflammatory cells and the levels of IL-1β, IL-18, IL-5 and IL-17 in the BALF of the experimental group were significantly lower than those of the model group after DEX treatment. DEX also significantly inhibited the activity of NLRP3 inflammasome and reduced the protein contents of Pro-Caspase-1, Caspase-1, Capase-1/Pro-Caspase-1, IL-1β, IL-6 and IL-17 in lung tissues. Our study suggested that DEX alleviates allergic airway inflammation by inhibiting the activity of NLRP3 inflammasome and the levels of IL-1β and IL-18.     

Apolipoprotein E negatively regulates murine allergic airway inflammation via suppressing the activation of NLRP3 inflammasome and oxidative stress

Apolipoprotein E (ApoE) has been reported as a steroid unresponsive gene and functions as a negative regulator of airway hyperreactivity (AHR) and goblet cell hyperplasia in house dust mite (HDM)-challenged mice. However, the role of ApoE in Ovalbumin (OVA)-induced allergic airway inflammation disease and the underlying mechanism are still unknown. In the present study, murine allergic airway inflammation was induced by inhaled OVA for consecutive 7 days in wild type (WT) and ApoE^−/− mice. In the OVA-induced model, the ApoE level in the bronchoalveolar lavage fluid (BALF) and lung tissues was significantly higher than that of control mice. And ApoE deficiency aggravated airway inflammation including leukocytes infiltration, goblet cell hyperplasia and IgE production as compared to those of WT mice after OVA- challenged, suggesting ApoE servers as an endogenous negative regulator of airway inflammation. Furthermore, OVA challenge elevated the activation of NLRP3 inflammasome with higher protein expression of NLRP3, caspase1 and IL-1β, enhanced oxidative stress with higher expression of 8-OHdG, nitrotyrosine and SOD2, increased the expression of mitochondrial fusion/fission markers including Optic Atrophy 1 (OPA1), Mitofusion 2 (Mfn2), dynamin-related protein 1 (DRP1) and Fission 1 (Fis1). However, these OVA-induced changes were augmented in ApoE^−/− mice. Collectively, our results demonstrated that the OVA-induced airway inflammation was aggravated in ApoE^−/− mice, and suggested that the underlying mechanism may be associated with the augmented activation of NLRP3 inflammasome and oxidative stress in ApoE^−/− mice, therefore targeting ApoE pathway might be a novel therapy approach for allergic airway diseases such as asthma.     

NLRP3 inflammasome activation is associated with PM2.5‐induced cardiac functional and pathological injury in mice

Growing evidences indicate that inflammation induced by PM_2.5 exposure has been considered as a major driving force for the development of cardiovascular diseases. However, the mechanisms underlying PM_2.5‐induced cardiac injury remain unclear. This study aims to investigate the role of NLRP3 inflammasome in PM_2.5‐induced cardiac functional and pathological injury in mice. In this study, BALB/c mice were intratracheally instilled with PM_2.5 suspension (4.0 mg/kg BW) for 5 days to set up a cardiac injury model, which was evaluated by electrocardiogram monitoring, HE and Masson staining. Then, the effects of PM_2.5 on the expression of α‐SMA, NLRP3, IL‐1β, and IL‐18 proteins and the activation of caspase‐1 and IL‐1β were investigated. The results showed that PM_2.5 exposure induced characteristic abnormal ECG changes such as the abnormality of heart rhythm, tachycardia, and T‐wave reduction. Inflammatory cell infiltration and fibrosis were observed in the heart tissues of PM_2.5‐exposed mice. Meanwhile, PM_2.5 exposure increased the expression of α‐SMA. And, NLRP3 activation‐associated proteins of NLRP3, IL‐1β, IL‐18, Cleaved caspase‐1 p10, and Cleaved IL‐1β were upregulated in heart tissue of PM_2.5‐induced mice. In summary, PM_2.5 exposure could induce cardiac functional and pathological injury, which may be associated with the activation of NLRP3 inflammasome.     

Hydroxysafflor yellow A inhibits hypoxia/reoxygenation-induced cardiomyocyte injury via regulating the AMPK/NLRP3 inflammasome pathway

Hydroxysafflor yellow A (HSYA) is an effective therapeutic agent that alleviates myocardial ischaemia/reperfusion injury (MIRI), but the exact mechanisms remain elusive. The aim of this study was to investigate the potential protective effect of HSYA against MIRI through mechanisms related to NLRP3 inflammasome regulation. In this study, hypoxia/reoxygenation (H/R)-induced H9c2 cardiomyocytes were treated with HSYA or the AMPK inhibitor, compound C (CC). Our results showed that HSYA pretreatment improved cardiomyocyte viability, maintained mitochondrial membrane potential, reduced apoptotic cardiomyocytes, decreased caspase-3 activity, and inhibited NOD-like receptor 3 (NLRP3) inflammasome activation during H/R injury. Moreover, the inhibition of AMPK activation by the CC inhibitor partially abolished the effects of HSYA treatment, including suppressing the upregulation of NLRP3 inflammasome components (NLRP3, caspase-1 and interleukin-1β) and promoting autophagy (LC3-II/LC3-I and p62). In conclusion, the protective mechanism of HSYA in H/R-induced cardiomyocyte injury is associated with inhibiting NLRP3 inflammasome activation through the AMPK signalling pathway.     

白藜芦醇对急性肝损伤小鼠NLRP3炎性体表达的影响

目的观察白藜芦醇对急性肝损伤(acute liver injury,ALI)小鼠Nod样受体家族3(Nod-like receptor 3,NLRP3)炎性体表达的影响,探讨白藜芦醇对ALI的保护作用及其机制。方法本实验采用四氯化碳制作ALI小鼠模型。将雄性ICR小鼠随机分成正常对照组、模型组、白藜芦醇低、中、高剂量组及阳性对照组,每组7只。白藜芦醇低、中、高剂量组及阳性对照组于造模前24 h及1 h分别腹腔注射剂量为10、20及30 mg/kg的白藜芦醇或剂量为100 mg/kg的乙酰半胱氨酸,对照组及模型组在相应时间点腹腔注射等量生理盐水,造模时模型组及各药物干预组采用腹腔注射5%四氯化碳,对照组腹腔注射等量橄榄油。采用蛋白质印迹(Western blot,WB)法测定小鼠肝组织NLRP3、凋亡相关微粒蛋白(apoptosis-associated speck-like protein contain,ASC)、炎性半胱天冬酶-1(caspase-1)蛋白,酶联免疫吸附测定(enzyme linked immunosorbent assay,ELISA)法检测炎症因子白介素(interleukin,IL)-1β及IL-18,全自动生化分析仪测定小鼠肝功能,病理组织学观察肝脏损伤情况及其程度。结果模型组小鼠谷丙转氨酶(alanine aminotransferase,ALT)及谷草转氨酶(aspartate aminotransferase,AST)水平高于正常对照组(P<0.01);白藜芦醇各剂量组及阳性对照组小鼠ALT及AST水平均低于模型组(P<0.01)。模型组小鼠肝脏炎症积分及损伤面积均高于正常对照组(P<0.01);白藜芦醇各剂量组及阳性对照组小鼠肝脏炎症积分及损伤面积均低于模型组(P<0.05或P<0.01)。模型组小鼠NLRP3、ASC、caspase-1、IL-1β及IL-18表达高于正常对照组(P<0.01);白藜芦醇各剂量组及阳性对照组小鼠NLRP3、ASC、caspase-1、IL-1β及IL-18表达均低于模型组(P<0.05或P<0.01)。病理组织切片显示,模型组小鼠肝细胞结构表现为胞浆疏松,小叶内坏死灶较多,坏死灶中可见中性粒细胞浸润;白藜芦醇各剂量组及阳性对照组小叶内坏死灶及中性粒细胞浸润等改变较模型组减少,肝细胞的受损面积较小。结论白藜芦醇可以显著减轻四氯化碳诱导的ALI,其机制可能与抑制NLRP3炎性体活化及其下游炎症级联反应有关。     

PFOS facilitates liver inflammation and steatosis: An involvement of NLRP3 inflammasome-mediated hepatocyte pyroptosis

Perfluorooctane sulfonate (PFOS) is a fluorinated organic pollutant with substantial accumulation in mammalian liver tissues. However, the impact of chronic PFOS exposure on liver disease progression and the underlying molecular mechanisms remain elusive. Herein, we for the first time revealed that micromolar range of PFOS exposure initiates the activation of NLR pyrin domain containing 3 (NLRP3) inflammasome to drive hepatocyte pyroptosis. We showed that 5 mg/kg/day PFOS exposure may exacerbated liver inflammation and steatosis in high-fat diet (HFD)-fed mice with concurrently elevated expression of NLRP3 and caspase-1. PFOS exposure resulted in viability impairment and LDH release in BRL-3A rat liver cells. 25–100 μM concentrations of PFOS exposure activated the NLRP3 inflammasome, leading to consequent GSDMD cleavage, IL-1β release and the initiation of pyroptosis in a dose-dependent manner, whereas treatment with 10 μM NLRP3 inhibitor MCC950 abrogated this effect. Moreover, pretreatment of 5 mM ROS scavenger N-acetyl-L-cysteine (NAC) ameliorated PFOS-induced NLRP3 inflammasome activation and pyroptosis. Collectively, our data highlight a pivotal role of pyroptotic death in PFOS-mediated liver inflammation and metabolic disorder.     

NLRP3炎性小体与糖尿病心肌病的发生发展

糖尿病心肌病(DCM)是糖尿病特异性心脏并发症,可独立于冠状动脉疾病、高血压或瓣膜性心脏病发生。目前公认的发病机制包括高血糖、蛋白非酶糖基化、氧化应激、钙离子转运异常等,其中炎症是导致左心室舒张功能障碍的独立因素。NLRP3是最常见的炎性小体,可诱导分泌IL-1β、IL-18等促炎细胞因子以及介导细胞焦亡。DCM发生时NLRP3表达上调,加剧胰岛β细胞功能受损、心肌损伤、心肌纤维化进程。已有研究证实,中药可通过抑制NLRP3炎性小体的启动和活化,以及其下游基因的表达,改善DCM心脏功能。本文就NLRP3炎性小体参与DCM发生及中药干预作用进行综述。     

雷公藤红素调控NLRP3炎症小体改善大鼠代谢相关脂肪性肝病研究

目的 评价雷公藤红素对高脂饮食诱导的代谢相关脂肪性肝病（MAFLD）大鼠的保护作用,并探讨其可能的作用机制。方法 60只健康雄性Wistar大鼠,随机分为6组：对照组、模型组、水飞蓟素胶囊组（阳性对照,100 mg·kg⁻¹）和雷公藤红素低、中、高剂量（125、250、500 μg·kg⁻¹）组,每组10只。对照组给予普通饲料喂养,其余5组给予高脂饲料喂养建立MAFLD模型,造模4周后,从第5周开始给药,ig给予相应剂量的药物至第8周。记录大鼠体质量和肝脏湿质量,计算肝脏系数;腹主动脉取血,检测大鼠血清中丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、三酰甘油（TG）、总胆固醇（TC）、低密度脂蛋白-胆固醇（LDL-C）、高密度脂蛋白-胆固醇（HDL-C）、肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）水平;HE染色观察肝脏病理变化;Western blotting法检测肝脏中NOD样受体热蛋白结构域相关蛋白3（NLRP3）和半胱氨酸蛋白酶-1（Caspase-1）蛋白表达水平。结果 与模型组比较,雷公藤红素各剂量组的肝脏病理学表现均有所改善,肝脏系数均显著降低（P＜0.05、0.01）;中、高剂量组大鼠血清中TC、TG、LDL-C、AST、ALT、TNF_-α和IL-1β水平均显著降低（P＜0.05、0.01）;肝脏中NLRP3和Caspase-1的蛋白表达显著减少（P＜0.05、0.01）。结论 雷公藤红素可明显减轻MAFLD大鼠的肝脏病理学损伤,改善血脂水平,其机制可能与调控NLRP3通路密切相关。     

Acetylase inhibitor SI-2 is a potent anti-inflammatory agent by inhibiting NLRP3 inflammasome activation

Aberrant activation of Nod-like receptor family pyrin domain-containing-3 (NLRP3) inflammasome is implicated in a variety of inflammatory diseases. Targeting NLRP3 inflammasome represents a promising therapy to cure such diseases. We and others recently demonstrated that acetylation of NLRP3 promotes the inflammasome activity and also suggested lysine acetyltransferases inhibitors could be a kind of promising agents for treating NLRP3 associated disorders. In this study, by searching for kinds of lysine acetyltransferases inhibitors, we showed that SI-2 hydrochloride (SI-2), a specific inhibitor of lysine acetyltransferase KAT13B (lysine acetyltransferases 13B), specifically blocks NLRP3 inflammasome activation both in mice in vivo and in human cells ex vivo. Intriguingly, SI-2 does not affect the acetylation of NLRP3. Instead, it disrupts the interaction between NLRP3 and adaptor apoptosis-associated speck-like protein containing CARD (ASC), then blocks the formation of ASC speck. Thus, our study identified a specific inhibitor for NLRP3 inflammasome and suggested SI-2 as a potential inhibitory agent for the therapy of NLRP3-driven diseases.     

中医药调控NLRP3炎性小体治疗脓毒症的研究进展

脓毒症（sepsis）是目前最普遍的感染性疾病之一,炎性反应是脓毒症由轻度转化为脓毒症休克的重要机制。NOD样受体蛋白3（NOD-like receptor protein 3,NLRP3）炎性小体是人体内的一种蛋白复合物,受多种因素调控,可触发机体的免疫反应与细胞焦亡。当体内NLRP3炎性小体调控机制失衡,过度的炎性...     

Pristimerin protects against inflammation and metabolic disorder in mice through inhibition of NLRP3 inflammasome activation

Excessive activation of NLRP3 inflammasome is associated with the pathogenesis of inflammatory diseases. Pristimerin (Pri) is a quinonoid triterpene derived from traditional Chinese medical herb Celastraceae and Hippocrateaceae. Pri has shown antifungal, antibacterial, antioxidant, and anticancer activities. In this study we investigated whether NLRP3 inflammasome was associated with the anti-inflammatory activity of Pri. We showed that Pri (0.1−0.4 μM) dose-dependently blocked caspase-1 activation and IL-1β maturation in LPS-primed mouse bone-marrow-derived macrophages (BMDMs). Pri specifically inhibited NLRP3 inflammasome activation, had no visible effects on NLRC4 and AIM2 inflammasome activation. Furthermore, we demonstrated that Pri blocked the assembly of the NLRP3 inflammasome via disturbing the interaction between NEK7 and NLRP3; the α, β-unsaturated carbonyl moiety of Pri was essential for NLRP3 inflammasome inactivation. In LPS-induced systemic inflammation mouse model and MSU-induced mouse peritonitis model, preinjection of Pri (500 μg/kg, ip) produced remarkable therapeutic effects via inhibition of NLRP3 inflammasome in vivo. In HFD-induced diabetic mouse model, administration of Pri (100 μg· kg⁻¹ ·d⁻¹, ip, for 6 weeks) reversed HFD-induced metabolic disorders via suppression of NLRP3 inflammasome activation. Taken together, our results demonstrate that Pri acts as a NLRP3 inhibitor, suggesting that Pri might be useful for the treatment of NLRP3-associated diseases.     

GPR84 signaling promotes intestinal mucosal inflammation via enhancing NLRP3 inflammasome activation in macrophages

The putative medium-chain free fatty acid receptor GPR84 is a G protein-coupled receptor primarily expressed in myeloid cells that constitute the innate immune system, including neutrophils, monocytes, and macrophages in the periphery and microglia in the brain. The fact that GPR84 expression in leukocytes is remarkably increased under acute inflammatory stimuli such as lipopolysaccharide (LPS) and TNFα suggests that it may play a role in the development of inflammatory and fibrotic diseases. Here we demonstrate that GPR84 is highly upregulated in inflamed colon tissues of active ulcerative colitis (UC) patients and dextran sulfate sodium (DSS)-induced colitis mice. Infiltrating GPR84⁺ macrophages are significantly increased in the colonic mucosa of both the UC patients and the mice with colitis. Consistently, GPR84^−/− mice are resistant to the development of colitis induced by DSS. GPR84 activation imposes pro-inflammatory properties in colonic macrophages through enhancing NLRP3 inflammasome activation, while the loss of GPR84 prevents the M1 polarization and properties of proinflammatory macrophages. CLH536, a novel GPR84 antagonist discovered by us, suppresses colitis by reducing the polarization and function of pro-inflammatory macrophages. These results define a unique role of GPR84 in innate immune cells and intestinal inflammation, and suggest that GPR84 may serve as a potential drug target for the treatment of UC.     

FTY720 inhibits tubulointerstitial inflammation in albumin overload-induced nephropathy of rats via the Sphk1 pathway

Aim:

FTY720, a new immunomodulatory drug with low cytotoxicity, is currently used to treat multiple sclerosis. In this study, we investigated the effects of FTY720 on inflammatory cell infiltration in albumin overload-induced nephropathy of rats.

Methods:

Male Wistar rats were subjected to right-side nephrectomy and divided into 3 groups. One week after the surgery, albumin overload (AO) group was treated with BSA (5 g·kg⁻¹·d⁻¹, ip) for 9 weeks; AO+FTY720 group was given BSA (5 g·kg⁻¹·d⁻¹, ip) plus FTY720 (0.5 g·kg⁻¹·d⁻¹, ip) for 9 weeks; and control group received daily ip injection of equivalent volume of saline. All rats were killed 9 weeks after nephrectomy.

Results:

AO rats exhibited gradually increased urinary protein excretion accompanied by elevated urinary N-acetyl-β-O-glucosaminidase activity, and both reached their peak values at week 7. Furthermore, AO significantly increased lymphocytes and monocytes in circulation and the inflammatory cells recruited to tubulointerstitium, and the expression of inflammatory cytokines MCP-1, TNF-α and IL-6, as well as sphingosine 1-phosphate (S1P) receptors S1pr1 and S1pr3, and S1P-synthesizing enzyme sphingosine kinase 1 (Sphk1) in the kidney. Concomitant administration of FTY720 significantly attenuated all the AO-induced pathological changes.

Conclusion:

FTY720 alleviates tubulointerstitium inflammation in an AO rat model of nephropathy via down-regulation of the Sphk1 pathway.     

Pramipexole inhibits astrocytic NLRP3 inflammasome activation via Drd3-dependent autophagy in a mouse model of Parkinson’s disease

Inflammation is one of the pathogenic processes in Parkinson’s disease (PD). Dopamine receptor agonist pramipexole (PPX) is extensively used for PD treatment in clinics. A number of studies show that PPX exerts neuroprotection on dopaminergic (DA) neurons, but the molecular mechanisms underlying the protective effects of PPX on DA neurons are not fully elucidated. In the present study, we investigated whether PPX modulated PD-related neuroinflammation and underlying mechanisms. PD model was established in mice by bilateral striatum injection of lipopolyssaccharide (LPS). The mice were administered PPX (0.5 mg·kg⁻¹·d⁻¹, i.p.) 3 days before LPS injection, and for 3 or 21 days after surgery, respectively, for biochemical and histological analyses. We showed that PPX administration significantly alleviated the loss of DA neurons, and suppressed the astrocyte activation and levels of proinflammatory cytokine IL-1β in the substantia nigra of LPS-injected mice. Furthermore, PPX administration significantly decreased the expression of NLRP3 inflammasome-associated proteins, i.e., cleaved forms of caspase-1, IL-1β, and apoptosis-associated speck-like protein containing a caspase recruit domain (ASC) in the striatum. These results were validated in LPS+ATP-stimulated primary mouse astrocytes in vitro. Remarkably, we showed that PPX (100–400 μM) dose-dependently enhanced the autophagy activity in the astrocytes evidenced by the elevations in LC3-II and BECN1 protein expression, as well as the increase of GFP-LC3 puncta formation. The opposite effects of PPX on astrocytic NLRP3 inflammasome and autophagy were eliminated by Drd3 depletion. Moreover, we demonstrated that both pretreatment of astrocytes with autophagy inhibitor chloroquine (40 μM) in vitro and astrocyte-specific Atg5 knockdown in vivo blocked PPX-caused inhibition on NLRP3 inflammasome and protection against DA neuron damage. Altogether, this study demonstrates an anti-neuroinflammatory activity of PPX via a Drd3-dependent enhancement of autophagy activity in astrocytes, and reveals a new mechanism for the beneficial effect of PPX in PD therapy.     

Costunolide covalently targets NACHT domain of NLRP3 to inhibit inflammasome activation and alleviate NLRP3-driven inflammatory diseases

The NLRP3 inflammasome’s core and most specific protein, NLRP3, has a variety of functions in inflammation-driven diseases. Costunolide (COS) is the major active ingredient of the traditional Chinese medicinal herb Saussurea lappa and has anti-inflammatory activity, but the principal mechanism and molecular target of COS remain unclear. Here, we show that COS covalently binds to cysteine 598 in NACHT domain of NLRP3, altering the ATPase activity and assembly of NLRP3 inflammasome. We declare COS’s great anti-inflammasome efficacy in macrophages and disease models of gouty arthritis and ulcerative colitis via inhibiting NLRP3 inflammasome activation. We also reveal that the α-methylene-γ-butyrolactone motif in sesquiterpene lactone is the certain active group in inhibiting NLRP3 activation. Taken together, NLRP3 is identified as a direct target of COS for its anti-inflammasome activity. COS, especially the α-methylene-γ-butyrolactone motif in COS structure, might be used to design and produce novel NLRP3 inhibitors as a lead compound.     

NLRP3炎症小体与心房颤动的研究进展

心房颤动（AF）是临床最常见的快速性心律失常,其发生机制尚未完全阐明,而炎症反应增强常与AF的发生发展相关。核苷酸结合寡聚化结构域受体蛋白3（NLRP3）作为近年研究最为广泛最具特征性的炎症小体,参与诸多非感染性炎性反应。有证据显示其与心房重构、心肌纤维化密切相关,以此入手可为阐明AF的上游机制提供新的理论基础和研究靶点。本文简述了NLRP3的特性及信号传导途径,从基础和临床研究两方面总结了NLRP3与AF的相关性,并对未来NLRP3拮抗剂的应用作出了展望。     

益母草碱抑制NLRP3炎症小体过度激活调控巨噬细胞M1/M2表型分化

目的 研究益母草碱对脂多糖(LPS)诱导小鼠腹腔巨噬细胞免疫应答影响及相关机制.方法 分离小鼠腹腔巨噬细胞,用脂多糖和益母草碱预处理24 h,MMT法检测巨噬细胞活性;Griess法检测NO释放量;ELISA法检测IL-1β、IL-18、IL-6、TNF-α的释放量;RT-PCR法检测NLRP3、ASC、caspase...     

荔枝核总黄酮对肝纤维化大鼠肝脏NLRP3表达的影响

目的 研究荔枝核总黄酮(total flavones from Lychee seed, TFL)对二甲基亚硝胺(dimethylnitrosamine, DMN)所诱发的肝脏纤维化大鼠肝脏中核苷酸结合寡聚化结构域样受体蛋白3(nucleotide-binding oligomerization domain-like receptor protein 3,NLRP3)表达的影响。方法 研究将Wistar雄性大鼠随机分为正常组、模型组、扶正化瘀组和荔枝核总黄酮高、中、低剂量组。ELISA法测定血清中羟脯氨酸、透明质酸、Ⅳ型胶原、Ⅲ型前胶原和层粘连蛋白的水平;HE染色和Masson染色观察大鼠肝脏组织的病理变化;RT-qPCR测定肝脏组织中硫氧还蛋白结合蛋白(thioredoxin-interacting protein, TXNIP)、核苷酸结合寡聚化结构域样受体蛋白3、半胱氨酸天冬氨酸蛋白酶-1(cysteine-aspartic proteases-1,caspase-1)、白细胞介素-1β(interleulin-1β,IL-1β)的mRNA表达水平。结果 荔枝核总黄酮减轻大鼠肝...