ACTA PHARMACOLOGICA SINICA
·
2024
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IF 6.9
Wang Fei,Wang Yu,Zhang Qing-yang,Hu Ke-yu,Song Ying-jie,Yang Lin,Fei Fan,Xu Ceng-lin,Cui Sun-liang,Ruan Ye-ping,Wang Yi,Chen Zhong
Status epilepticus (SE), a serious and often life-threatening medical emergency, is characterized by abnormally prolonged seizures. It is not effectively managed by present first-line anti-seizure medications and could readily develop into drug resistance without timely treatment. In this study, we highlight the therapeutic potential of CZL80, a small molecule that inhibits caspase-1, in SE termination and its related mechanisms. We found that delayed treatment of diazepam (0.5 h) easily induces resistance in kainic acid (KA)-induced SE. CZL80 dose-dependently terminated diazepam-resistant SE, extending the therapeutic time window to 3 h following SE, and also protected against neuronal damage. Interestingly, the effect of CZL80 on SE termination was model-dependent, as evidenced by ineffectiveness in the pilocarpine-induced SE. Further, we found that CZL80 did not terminate KA-induced SE in Caspase-1 −/− mice but partially terminated SE in IL1R1 −/− mice, suggesting the SE termination effect of CZL80 was dependent on the caspase-1, but not entirely through the downstream IL-1β pathway. Furthermore, in vivo calcium fiber photometry revealed that CZL80 completely reversed the neuroinflammation-augmented glutamatergic transmission in SE. Together, our results demonstrate that caspase-1 inhibitor CZL80 terminates diazepam-resistant SE by blocking glutamatergic transmission. This may be of great therapeutic significance for the clinical treatment of refractory SE.
研究领域:
神经科学
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药理学
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神经炎症
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癫痫
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DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
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2024
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IF 6.8
Dongyi Cao,Ruiying Xi,Hongye Li,Zhonghui Zhang,Xiaoke Shi,Shanshan Li,Yujie Jin,Wanli Liu,Guolin Zhang,Xiaohua Liu,Shunxi Dong,Xiaoming Feng,Fei Wang
Caspase-1 plays a central role in innate immunity, as its activation by inflammasomes induces the production of proinflammatory cytokines and pyroptosis. However, specific inhibition of the enzymatic activity of this protease is not effective in suppressing inflammation, owing to its enzyme-independent function. Herein, we identified a cyclohexenyl isothiocyanate compound (CIB-1476) that potently inhibited caspase-1 activity and suppressed the assembly and activation of the NLRP3 inflammasome and gasdermin-D-mediated pyroptosis. Mechanistically, CIB-1476 directly targeted pro-caspase-1 as an irreversible covalent inhibitor by binding to Cys285 and Cys397, resulting in more durable anti-inflammatory effects in the suppression of enzyme-dependent IL-1β production and enzyme-independent nuclear factor κB activation. Chemoproteomic profiling demonstrated the engagement of CIB-1476 with caspase-1. CIB-1476 showed potent therapeutic effects by suppressing inflammasome activation in mice, which was abolished in Casp1–/– mice. These results warrant further development of CIB-1476 along with its analogues as a novel strategy for caspase-1 inhibitors.
研究领域:
免疫学
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药理学
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生物化学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Mengze Ding,Xiaohan Wei,Changshun Liu,Xiaomei Tan
Ethnopharmacological relevance Allergic rhinitis (AR) is a prevalent nasal inflammatory disorder, and pyroptosis plays a crucial role in aggravating AR. Current medications for AR treatment still have deficiencies, and finding new agents is of great interest. Mahuang Fuzi Xixin decoction (MFXD), an ancient Chinese medicine, is now commonly used to treat AR, which has anti-inflammatory and immunomodulatory effects, but its underlying mechanism is unknown. Aim of this study This study aims to evaluate the effects of MFXD on AR and explore its potential mechanisms in view of the regulatory effect on pyroptosis. Methods MFXD, Mahuang, Fuzi, and Xixin water extracts were analyzed using ultra high performance liquid chromatography-Orbitrap-high-resolution accurate mass spectrometry. In in vivo study, the effects of MFXD on AR treatment were evaluated in an ovalbumin-induced mouse model. Mice were administered saline (control and model groups), MFXD (1.375, 2.75 g/kg), and dexamethasone (2.5 mg/kg) for 13 days. AR symptoms were evaluated by blinded observers. Immunoglobulin E (IgE) and histamine levels were measured using enzyme-linked immunosorbent assays. Expression of pyroptosis-related proteins (NLRP3, ASC, Caspase-1 p10/p20, GSDMD-N and IL-1β) in AR mouse nasal mucosa were estimated by immunohistochemistry. In in vivtro study, the effects of MFXD on pyroptosis were assessed in human nasal epithelial cells (HNEpCs) stimulated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP), and incubated with MFXD (12.5, 25, and 50 μg/mL). Pyroptosis-related protein expression was measured by western blotting. Results Thirty-three compounds in MFXD were identified, including ephedrine, pseudoephedrine, higenamine, aconine, aconitine, benzoylmesaconitine, benzoylhypaconine and hypaconitine. In the in vivo study, oral taken of MFXD/dexamethasone significantly ameliorated AR symptoms, reduced swelling of the nasal mucosa, and decreased the levels of IgE and histamine in AR mice serum. MFXD/dexamethasone attenuated histopathological changes and reduced the expression of pyroptosis-related proteins in nasal mucosa, indicating the inhibitory effect on nasal epithelial pyroptosis. In the in vitro study, MFXD (50 μg/mL) significantly alleviated cytotoxicity, protected cells from swelling and rupture, and downregulated the expression of pyroptosis-related proteins in LPS/ATP-induced HNEpCs. Conclusion MFXD suppressed nasal epithelial pyroptosis by inhibiting the NLRP3/Caspase-1/GSDMD-N signaling pathway, which alleviates AR. Our results offer valuable insights into potential AR therapies and provide evidence for the clinical utilization of MFXD to treat AR.
研究领域:
药理学
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免疫学
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民族药理学
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炎症
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中医
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产品关联
DOI
PubMed
高影响因子
Cell Reports
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2024
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IF 7.5
Xueping Li,Jiarui Zhou,Xingmei Liu,Chen Jin,Le Liu,Hongmin Sun,Qian Wang,Qiushi Wang,Ruiying Liu,Xiaoyu Zheng,Yutao Liu,Yu Pang
Uropathogenic Escherichia coli (UPEC) is the most common causative agent of urinary tract infection (UTI). UPEC invades bladder epithelial cells (BECs) via fusiform vesicles, escapes into the cytosol, and establishes biofilm-like intracellular bacterial communities (IBCs). Nucleoside-diphosphate kinase (NDK) is secreted by pathogenic bacteria to enhance virulence. However, whether NDK is involved in UPEC pathogenesis remains unclear. Here, we find that the lack of ndk impairs the colonization of UPEC CFT073 in mouse bladders and kidneys owing to the impaired ability of UPEC to form IBCs. Furthermore, we demonstrate that NDK inhibits caspase-1-dependent pyroptosis by consuming extracellular ATP, preventing superficial BEC exfoliation, and promoting IBC formation. UPEC utilizes the reactive oxygen species (ROS) sensor OxyR to indirectly activate the regulator integration host factor, which then directly activates ndk expression in response to intracellular ROS. Here, we reveal a signaling transduction pathway that UPEC employs to inhibit superficial BEC exfoliation, thus facilitating acute UTI.
研究领域:
微生物学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Aging-US
·
2023
·
IF 5.2
Guang-Zhi Liu,Tian-Tong Niu,Qian Yu,Bao-Lei Xu,Xiao-Qing Li,Bo-Yi Yuan,Guo-Bin Yuan,Ting-Ting Yang,Hui-Qin Li,Yi Sun
The NLRP3 inflammasome is involved in the neuroinflammatory pathway of Alzheimer’s disease (AD). The aim of this study is to explore the roles and underlying mechanisms of ginkgolide (Baiyu®) on amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice and a murine microglial cell line, BV-2. In the present study, the APP/PS1 mice were administered with ginkgolide, followed by a Morris water maze test. The mice were then euthanized to obtain brain tissue for histological and Aβ analysis. Additionally, BV-2 cells were pretreated with ginkgolide and then incubated with Aβ1–42 peptide. NLRP3, ASC, and caspase-1 mRNA and protein expression in brain tissue of mice and BV-2 cells were quantified by real-time PCR and western blotting, as well as reactive oxygen species (ROS) production, interleukin (IL)-1β and IL-18 levels by lucigenin technique and ELISA. Compared with the APP/PS1 mice, ginkgolide-treated mice demonstrated the shortened escape latency, reduced plaques, less inflammatory cell infiltration and neuron loss in the hippocampi of APP/PS1 mice. The levels of NLRP3, ASC, caspase-1, ROS, IL-1β, and IL-18 were also decreased in the brain tissue of APP/PS1 mice or Aβ1–42-treated BV-2 cells following ginkgolide treatment. Ginkgolide exerted protective effects on AD, at least partly by inactivating the NLRP3/caspase-1 pathway.
研究领域:
神经科学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
LIFE SCIENCES
·
2021
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IF 5.037
Zhenjie Sun,Qian Chai,Ziying Zhang,Dexue Lu,Ziang Meng,Weihua Wu
Aims Glycemic variability has been shown to be more harmful in the development of diabetic complication than sustained chronic hyperglycemia. In this present study, we tried to reveal the effects of glycemic variability on cardiac damage in diabetic mice and investigate whether sodium-glucose cotransporter 1 (SGLT1), an important cardiac glucose transporter, functions as an important mediator in the process. Materials and methods Type 2 diabetes mellitus (DM) mice were induced by a high-fat diet and intraperitoneal injection of streptozotocin (STZ), and then glycemic variability in type 2 diabetes mellitus (GVDM) was induced by alternately injecting insulin and glucose to DM mice. In order to determine the roles of SGLT1 in GVDM mice, SGLT1 inhibition was performed using shRNA against SGLT1. The blood glucose level, the cardiac function and myocardial injury were assessed. And the expressions of SGLT1 and the activations of NLRP3/caspase-1 pathway and NF-κB in left ventricular tissues were measured. Key findings The results showed that SGLT1 was highly expressed in heart of GVDM mice compared to control and DM groups, and knockdown of SGLT1 reduced glycemic variability in GVDM mice. Moreover, glycemic variability impaired cardiac function, aggravated cardiac injury and induced NLRP3/caspase-1-mediated inflammatory response and pyroptosis. And knockdown of SGLT1 significantly attenuated the cardiac damages that induced by glycemic variability. Significance The results indicated that glycemic variability could cause cardiac damage and induce inflammatory response and pyroptosis of cardiomyocytes in diabetic mice, which could be partially blocked by SGLT1 silence.
研究领域:
内分泌学
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心脏病学
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糖尿病
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
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IF 4.7
Xiaolin Ma,Xuan Zhao,Yulong Yang,Jinjin Yan,Xiaoyan Shi,Hongfei Wu,Yarong Liu,Min Dai
Atherosclerosis is a chronic inflammatory disease characterized by lipid streaks, which are produced by aggregates of lipid-rich foam cells. Foam cells intensify atherosclerosis by secreting a range of inflammatory mediators. Neutrophil extracellular traps produced by activated neutrophils, which are abundantly present in lipid-accumulating plaques. However, the relationship between neutrophil extracellular traps and foam cells inflammation is still unclear. Paeonol is well known for its anti-inflammatory effects in atherosclerosis. Nevertheless, the exact pharmacological mechanisms by which paeonol affects atherosclerosis are not fully understood which require further investigation. The purpose of this study is to investigate the effects of paeonol on the neutrophil extracellular traps' formation and foam cell inflammation caused by neutrophil extracellular traps, and to explore the potential mechanisms. A high-fat diet was administered to ApoE −/− mice for a period of 12 weeks to induce an atherosclerosis model. Our findings demonstrated that paeonol notably suppressed the advancement of atherosclerosis in ApoE −/− mice, curtailed the formation of neutrophil extracellular traps, and lowered inflammatory factor levels within the plaque. In vitro studies have shown that neutrophil extracellular traps could enhance the inflammation in foam cells. CitH3 played a role in the cellular communication between neutrophil extracellular traps and foam cells. Concurrently, NLRP3 acted as a key receptor in the inflammation mediated by this interaction. Paeonol is capable of regulating NE, thereby affecting the formation of neutrophil extracellular traps. Most notably, the foam cell inflammation caused by neutrophil extracellular traps was significantly mitigated by the inclusion of paeonol. Our findings suggested that paeonol inhibited foam cell inflammation which induced by neutrophil extracellular traps through the CitH3/NLRP3/caspase-1 signaling pathway, shedding new lights on its anti-atherosclerotic pharmacological mechanism.
研究领域:
心血管疾病
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炎症
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2026
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IF 6.8
Chuanqi Wan,Jiamin Lu,Lingyun Xu,Mei Jiang,Chen Zhu,Wen Zhang,Pingping Han,Jirong Zhang,Jing Wang,Weiwei Ren,Hui Chu,Bingzhi Zhou,Jiancheng Zhang,Guangjun Jin,Bangjiang Fang,Yuzhou He
Shenhuang Granules (SHG) attenuate sepsis-induced lung injury via the NLRP3/Caspase-1/GSDMD pathway. • (−)-Epicatechin gallate and gallic acid are the core bioactive monomers of SHG against PMVEC pyroptosis. • SHG inhibits pyroptosis by suppressing inflammasome assembly and pore formation. Ethnopharmacological relevance Shenhuang Granules (SHG) is a traditional Chinese medicine (TCM) formula composed of six medicinal materials: Panax ginseng C.A. Mey. (Ginseng Radix et Rhizoma), Rheum palmatum L. (Rhei Radix et Rhizoma), Sargentodoxa cuneata (Oliv.) Rehder & E.H. Wilson (Sargentodoxae Caulis), Taraxacum mongolicum Hand. -Mazz. (Taraxaci Herba), Aconitum carmichaelii Debeaux (Aconiti Lateralis Radix Praeparata), and Whitmania pigra Whitman (Hirudo). According to TCM theory, this formula is designed to replenish Qi and strengthen the body's resistance, clear heat and remove toxins, and promote blood circulation to eliminate blood stasis. In clinical practice, SHG has been used as an adjunctive therapy for sepsis, showing beneficial effects in ameliorating systemic inflammatory responses and microcirculatory disturbances. However, the underlying pharmacological mechanisms remain largely unclear. Aim of the study To validate that SHG and its active monomers alleviate sepsis-induced lung injury through targeted suppression of the NLRP3-driven PMVEC pyroptosis pathway. Materials and methods The chemical composition of SHG was analyzed by UHPLC-MS/MS. In vivo, SA-ARDS was induced in C57BL/6J mice by cecal ligation and puncture (CLP), with SHG (61.85 mg/mouse/d), its monomers, (−)-epicatechin gallate (ECG) and gallic acid (GA) (20 mg/kg/d), or the NLRP3 inhibitor MCC950 (10 mg/kg/d), were administered via intraperitoneal injection for 3 days prior to modeling. Lung injury severity and activation of the pyroptosis pathway were evaluated using histopathology, transmission electron microscopy, RT-qPCR, Western blotting, immunohistochemistry, immunofluorescence, and ELISA. In vitro, LPS-stimulated (1 μg/mL) PMVECs were used to screen 43 monomers, and the underlying mechanisms were subsequently verified. Results Compared with the Model group, SHG treatment significantly attenuated body weight loss in mice ( P < 0.001), reduced the lung wet-to-dry (W/D) weight ratio ( P < 0.05), and decreased Evans blue extravasation in lung tissues ( P < 0.01). SHG also significantly downregulated the mRNA expression levels of pyroptosis-related genes, including Twik2 , Nlrp3 , Asc , Caspase-1 , and Gsdmd , in lung tissues (all P < 0.01), and markedly reduced the protein expression of NLRP3, ASC, pro-Caspase-1, and Caspase-1 (all P < 0.05). ELISA results further demonstrated that SHG significantly decreased serum levels of the inflammatory cytokines TNF-α, IL-1β, IFN-γ, IL-18, pro-IL-1β, and pro-IL-18 in mice (all P < 0.05). In vitro, compared with the Model group, SHG significantly suppressed the transcriptional levels of Twik2 , Nlrp3 , Asc , Caspase-1 , and Gsdmd in PMVECs (all P < 0.05), and reduced the protein expression of NLRP3, ASC, GSDMD, GSDMD-NT, and IL-1β (all P < 0.05). Additionally, SHG markedly decreased lactate dehydrogenase (LDH) release ( P < 0.0001) and attenuated extracellular potassium ion (K + ) efflux ( P < 0.0001). Notably, ECG and GA individually exhibited potent inhibitory effects on PMVEC pyroptosis. Compared with the Model group, both ECG and GA significantly suppressed mRNA expression of Twik2, Nlrp3, Asc, Caspase-1, and Gsdmd (all P < 0.05) and reduced protein levels of NLRP3 , ASC , Caspase-1 , and GSDMD (all P < 0.05). Moreover, ECG significantly inhibited GSDMD-NT and IL-1β protein expression (all P < 0.05). Both ECG and GA markedly reduced TNF-α, IL-1β, and pro-IL-18 levels (all P < 0.05), and GA additionally suppressed IL-18 and pro-IL-1β expression (all P < 0.01). Furthermore, both ECG and GA significantly decreased LDH release ( P < 0.0001) and inhibited extracellular K + efflux ( P < 0.0001). However, this study has several limitations, including a small sample size, the absence of dose-gradient and time-course analyses, insufficient functional validation of the TWIK2 channel, and the lack of quantitative pharmacokinetic and synergy analyses, which should be addressed in future studies. Conclusion Shenhuang Granules attenuated PMVEC pyroptosis and ameliorated sepsis-induced lung injury by suppressing TWIK2 and the downstream NLRP3/Caspase-1/GSDMD pathway, with GA and ECG as the key active components. Download: Download high-res image (484KB) Download: Download full-size image
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
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IF 4.8
Xi Ma,YuZheng Yang,Hao Li,ZeHong Luo,QiuYi Wang,XueMing Yao,Fang Tang,Ying Huang,Yi Ling,WuKai Ma
Although the pathogenesis of rheumatoid arthritis (RA) remains unclear, an increasing number of studies have confirmed that pyroptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) is an important factor affecting the progression of RA. Periplogenin (PPN) is a natural cardiac glycoside; reportedly, it exerts anti-inflammatory and analgesic effects in diseases by inhibiting cell growth and migration. This study aimed to determine the effect of PPN on the growth, migration, and invasion of RA-FLS and the potential mechanism of pyroptosis regulation. We discovered that PPN could inhibit the migration and invasion abilities of RA-FLS and block their growth cycle, down-regulate the secretion and activation of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18, and reduce the number of pyroptosis. In summary, PPN inhibited pyroptosis, reduced the release of inflammatory factors, and improved RA-FLS inflammation by regulating the NLRP3/Caspase-1/GSDMD signaling pathway.
研究领域:
药理学
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免疫学
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风湿病学
✓ 已验证
DOI
PubMed
高影响因子
Food Science & Nutrition
·
2024
·
IF 3.5
Ruixi Luo,Yudie Hu,La Wang,Zunli Ke,Wenjia Wang,Ping Wang,Weiyi Tian
The primary catalyst for nonalcoholic fatty liver disease (NAFLD) is widely recognized as the induction of lipotoxicity in hepatocytes by an excess of fatty acids. In China, Penthorum chinense Pursh (PcP) is commonly employed as a functional food due to its known hepatoprotective properties. The present study aimed to investigate the influence of PcP extract on in vivo and in vitro models of NAFLD. We found that PcP extract can attenuate palmitic acid (PA)-induced lipotoxicity in HepG2 cells. PA was observed to trigger pyroptosis, as indicated by the increased expression of NLRP3 and GSDMD/N, activation of Caspase-1, and subsequent release of IL-1β and IL-18. However, these changes were reversed after PcP was administered. Furthermore, the application of an NLRP3 agonist inhibited the protective effects of PcP on lipotoxicity, indicating that PcP decreased lipotoxicity by inhibiting the NLRP3/Caspase-1/GSDMD pathway. Ultimately, we established a rat model of NAFLD through the administration of a high-fat diet (HFD), followed by the oral delivery of PcP extracts. The results demonstrated that the administration of PcP extract effectively decreased dyslipidemia and hepatic steatosis, which coincided with a decrease in hepatic pyroptosis through modulation of the NLRP3/Caspase-1/GSDMD pathway in liver tissues. Overall, our findings provide insight into the mechanism by which PcP extracts alleviate hepatic steatosis, highlighting the potential significance of modulating the NLRP3/Caspase-1/GSDMD pathway in the context of pyroptosis.
研究领域:
药理学
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肝病学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2021
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IF 5.811
Zhang Xueyan,Liu Yingbo,Deng Guangrui,Huang Bisheng,Kai Guoyin,chen Keli,Li Juan
Background: Activation of nucleotide oligomerization domain-like receptor protein 3 (NLRP3) inflammasome plays a crucial role in gout. Selaginella moellendorffii has been confirmed effective for the treatment of gout in hospital preparations. Flavonoids, such as amentoflavone (AM), are the main active components of this medicine.Purpose: We aimed to investigate the flavonoid extract (TF) and AM's effects on NLRP3 inflammasome in vitro and their preventive effects on gout in vivo.Methods: LC-MS method was employed to investigate the chemical profile of TF. The cellular inflammation model was established by lipopolysaccharide (LPS) or monosodium urate (MSU) stimulation. The cell membrane integrality and morphological characteristics were determined by using Lactate dehydrogenase (LDH) assay kits, propidium iodide (PI) stain, and scanning electron microscopy (SEM). The inflammatory cytokines and NLRP3 inflammasome activation were determined using enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (RT-PCR), immunofluorescence staining, and western blotting. The acute gout mouse model was induced by MSU injection into footpads, and then the paw edema, inflammatory mediators, and histological examination (HE) were analyzed.Results: The main constituents in TF are AM and robustaflavone. In the cellular inflammation model, TF down-regulated the levels of nitric oxide (NO), TNF-α, and LDH, suppressed NLRP3 inflammasome-derived interleukin-1β (IL-1β) secretion, decreased caspase-1 activation, repressed mature IL-1β expression, inhibited ASC speck formation and NLRP3 protein expression. In an acute gout mouse model, oral administration of TF to mice effectively alleviated paw edema, reduced inflammatory features, and decreased the levels of IL-1β in mouse foot tissue. Similarly, the characteristic constituent AM was also able to down-regulated the levels of NO, TNF-α, and LDH, down-regulate the mRNA expression of IL-1β, TNF-α, caspase-1, and NLRP3. Besides, the foot thickness, lymphocyte infiltration, and IL-1β level were also prevented by AM.Conclusion: The results indicated that TF and its main constituent AM alleviate gout arthritis via NLRP3/ASC/Caspase-1 axis suppression.
研究领域:
药理学
·
免疫学
·
生物化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Jiajia Mu,Qiannan Sun,Nanyan Lin,Chenguang Yue,Jiaqiao Zhu,Hui Zou,Hongyan Zhao,Ruilong Song,Zongping Liu,Yonggang Ma
Ketosis in dairy cows is linked to endometritis, but the molecular mechanisms are unclear. We investigated whether P2X7R is crucial in ketosis-induced endometritis. Ketotic cows had higher levels of NLRP3, caspase-1, GSDMD, GSDME, and P2X7R in the uterine tissue. β-Hydroxybutyric acid (BHBA) exposure in bovine endometrial epithelial cells induced pyroptosis, increased pyroptosis protein and gene expression, and raised pyroptosis rates. P2X7R levels rose with BHBA, and BHBA also increased the level of extracellular ATP. Inhibitors of NLRP3, caspase-1, caspase-3, and P2X7R reduced BHBA-induced pyroptosis. P2X7R inhibition suppressed NLRP3, caspase-1, and caspase-3 activation, preventing pyroptosis. In P2rx7–/– mice with a ketosis model, blood BHBA was lower, and uterine tissue showed less pyroptosis-related protein expression compared to ketotic mice. P2X7R appears to regulate BHBA-induced pyroptosis through NLRP3 and caspase-3 signaling, suggesting it is a potential therapeutic target.
研究领域:
兽医学
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生殖生物学
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细胞生物学
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分子生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）