Experimental Animals最新文献_第3页

Remimazolam- and dexmedetomidine-based three-drug mixtures refine injectable anesthesia in mice. 以雷马唑仑和右美托咪定为基础的三药混合物改进了小鼠的注射麻醉。

IF 2 4区农林科学

Experimental Animals Pub Date : 2026-09-11 DOI: 10.1538/expanim.26-0126

Takeru Sasaki, Masaki Watanabe, Ryuya Nakagawa, Nobuya Sasaki

{"title":"Remimazolam- and dexmedetomidine-based three-drug mixtures refine injectable anesthesia in mice.","authors":"Takeru Sasaki, Masaki Watanabe, Ryuya Nakagawa, Nobuya Sasaki","doi":"10.1538/expanim.26-0126","DOIUrl":"https://doi.org/10.1538/expanim.26-0126","url":null,"abstract":"The medetomidine-midazolam-butorphanol mixture (MMB) is widely used for injectable anesthesia in mice but is associated with delayed induction, prolonged recovery, impaired oxygenation, and post-anesthetic hypothermia. We investigated whether substituting midazolam with remimazolam, alone or together with replacing medetomidine with dexmedetomidine, improved the anesthetic profile. Male C57BL/6JJcl mice (n=8/group) received intraperitoneal MMB, medetomidine-remimazolam-butorphanol (MRB), or dexmedetomidine-remimazolam-butorphanol (dMRB). Induction was assessed by times to immobilization and loss of the righting reflex (LORR), anesthetic depth by a study-specific 0-5 reflex-loss score, and recovery by time to return of the righting reflex (RORR). Oxygen saturation, heart rate, respiratory rate, and rectal temperature were monitored. Compared with MMB, MRB shortened times to immobilization, LORR, and RORR, whereas dMRB shortened LORR. The reflex-loss score showed no overall group effect or area under the curve (AUC) difference, although a significant interaction between group and time indicated different temporal profiles. No overall group main effects were detected for the physiological variables during anesthesia; however, measured SpO₂ was markedly low in all groups (pooled mean, 61.7 ± 6.6%). During recovery without external heating, rectal temperature differed among groups: the dMRB-MMB AUC comparison was significant, MRB-MMB was borderline, and MRB-dMRB was not significant. MRB improved induction and recovery timing, whereas dMRB improved induction and showed the strongest evidence of better recovery-phase thermoregulation; neither modification corrected the low measured SpO₂.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Route-dependent immune-inflammatory and tissue remodeling responses to BCG injection in mice. 小鼠卡介苗注射后通路依赖性免疫炎症和组织重塑反应。

IF 2 4区农林科学

Experimental Animals Pub Date : 2026-09-10 DOI: 10.1538/expanim.26-0049

Hui Liu, Wei Na, Aiqin Li, Songlin Guo, Wenling Chen, Ying Yang, Yonghong Yang, Lu Ding, Jinyuan Zhu, Xu Zhang

{"title":"Route-dependent immune-inflammatory and tissue remodeling responses to BCG injection in mice.","authors":"Hui Liu, Wei Na, Aiqin Li, Songlin Guo, Wenling Chen, Ying Yang, Yonghong Yang, Lu Ding, Jinyuan Zhu, Xu Zhang","doi":"10.1538/expanim.26-0049","DOIUrl":"https://doi.org/10.1538/expanim.26-0049","url":null,"abstract":"Bacillus Calmette-Guérin (BCG) activates innate immune responses, but its tissue effects depend on the route of administration. We compared intra-airway (IA) and intravenous (IV) BCG administration in female C57BL/6N mice using a matched longitudinal design from immediately after administration through day 28. Outcomes included body and organ weights, gross pathology, histology, collagen and iron deposition, and pulmonary inflammatory-marker expression. IA-BCG reduced body-weight gain and produced marked pulmonary inflammation, collagen deposition, and increased staining for inflammatory and fibrosis-related markers. IV-BCG caused minimal pulmonary injury but produced hepatosplenomegaly, periportal hepatic collagen deposition, splenic hemorrhage, and splenic iron accumulation. These findings define distinct route-associated tissue phenotypes under matched experimental conditions. IA administration provides a model for pulmonary inflammation and remodeling, whereas IV administration provides a model for hepato-splenic responses. Bacterial burden, immune-cell composition, and causal signaling pathways were not assessed.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Traditional Chinese herbal formula Huo Luo Xiao Ling Dan ameliorates rheumatoid arthritis by suppressing inflammation and oxidative stress via the AGE/RAGE/NF‑κB signaling pathway. 中药复方霍络消灵丹通过AGE/RAGE/NF - κB信号通路抑制炎症和氧化应激，改善类风湿关节炎。

IF 2 4区农林科学

Experimental Animals Pub Date : 2026-09-09 DOI: 10.1538/expanim.26-0076

Wenyan Yang, Ning Yang, Chao Xu, Pinpin Zhu, Liyun Luan

{"title":"Traditional Chinese herbal formula Huo Luo Xiao Ling Dan ameliorates rheumatoid arthritis by suppressing inflammation and oxidative stress via the AGE/RAGE/NF‑κB signaling pathway.","authors":"Wenyan Yang, Ning Yang, Chao Xu, Pinpin Zhu, Liyun Luan","doi":"10.1538/expanim.26-0076","DOIUrl":"https://doi.org/10.1538/expanim.26-0076","url":null,"abstract":"Rheumatoid arthritis (RA) is a chronic autoimmune pathology that arises chiefly from the dysregulated activation of fibroblast-like synoviocytes. The traditional Chinese herbal formula Huo Luo Xiao Ling Dan (HLXL) has unclear mechanisms in RA treatment. This work combined network pharmacology with both cellular and animal-based experiments. Network analysis suggested the advanced glycation end products (AGE)/receptor for advanced glycation end products (RAGE) pathway as a crucial target for HLXL. In vitro experiments showed that HLXL (50, 100 μg/mL) dose‑dependently suppressed TNF‑α‑induced MH7A human fibroblast-like synoviocyte proliferation, migration, invasion, and NF‑κB activation. Additionally, HLXL reduced oxidative stress markers (ROS, MDA) and pro‑inflammatory cytokines (IL‑6, IL‑1β), while enhancing total superoxide dismutase (tSOD) activity. The RAGE agonist D‑Ribose counteracted these effects, confirming the involvement of AGE/RAGE signaling. In collagen‑induced arthritis (CIA) rats, HLXL (7.25, 14.5 g/kg) ameliorated joint swelling, arthritis index, synovial pathology, and cartilage erosion. It also decreased oxidative stress and inflammatory factors in serum and synovial tissues and suppressed AGE/RAGE/NF‑κB signaling in vivo. Collectively, HLXL exerts anti‑RA effects through inhibition of the AGE/RAGE/NF‑κB pathway.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Spontaneous hepatocellular carcinoma in laboratory-reared degus (Octodon degus): histopathological and immunohistochemical characterization. 实验室饲养的章鱼自发性肝细胞癌：组织病理学和免疫组织化学特征。

IF 2 4区农林科学

Experimental Animals Pub Date : 2026-08-27 DOI: 10.1538/expanim.26-0066

Masato Inoh, Runa Yoshimura, Tamami Suzuki, Goro A Nagura-Kato, Akio Shinohara, Masami Morimatsu, Teppei Nakamura

{"title":"Spontaneous hepatocellular carcinoma in laboratory-reared degus (Octodon degus): histopathological and immunohistochemical characterization.","authors":"Masato Inoh, Runa Yoshimura, Tamami Suzuki, Goro A Nagura-Kato, Akio Shinohara, Masami Morimatsu, Teppei Nakamura","doi":"10.1538/expanim.26-0066","DOIUrl":"https://doi.org/10.1538/expanim.26-0066","url":null,"abstract":"The degu (Octodon degus), a highly intelligent rodent with unique communication abilities, has been used in various research fields. However, reports on spontaneous lesions in degus are limited. During routine examinations, we incidentally observed hepatic nodular lesions in laboratory-reared degus maintained at the University of Miyazaki. We aimed to investigate the prevalence and histopathological characteristics of hepatic nodular lesions in degus. The prevalence of these lesions increased with age, but no sex-related differences were observed. No gross abnormalities were noted in any organ other than the liver. Serum biochemistry revealed significantly higher aspartate aminotransferase levels in animals with hepatic nodules than in those without nodules. Histopathologically, the nodules were sharply demarcated from the normal hepatic parenchyma without fibrous encapsulation, and showed loss of lobular architecture and portal triads, along with markedly thickened hepatic cords. The nodular cells expressed arginase-1 and exhibited abundant clear cytoplasm, moderate anisocytosis, anisokaryosis, and glycogenated nuclei. Despite rare mitotic figures, the Ki67 labeling index of the neoplastic cells was significantly higher than that of normal hepatocytes. There was no evidence of epithelial mesenchymal transition in the lesions. Collectively, these hepatic nodules were diagnosed as spontaneously occurring, well-differentiated hepatocellular carcinomas. This is the first report to compile multiple cases of spontaneous hepatocellular carcinoma in degus. This study provides valuable background pathological information and supports the potential utility of degus as a laboratory animal model in hepatocellular neoplasia.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148826342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CCDC85C expression in rat glomeruli and its role in kidney development. CCDC85C在大鼠肾小球中的表达及其在肾脏发育中的作用。

IF 2 4区农林科学

Experimental Animals Pub Date : 2026-08-25 DOI: 10.1538/expanim.26-0046

Hisaki Tokuno, Miyuu Tanaka, Takeshi Izawa, Mitsuru Kuwamura

{"title":"CCDC85C expression in rat glomeruli and its role in kidney development.","authors":"Hisaki Tokuno, Miyuu Tanaka, Takeshi Izawa, Mitsuru Kuwamura","doi":"10.1538/expanim.26-0046","DOIUrl":"https://doi.org/10.1538/expanim.26-0046","url":null,"abstract":"Coiled-coil domain containing 85c (CCDC85C), a protein located at cell junctions, has attracted attention for its role in regulating cellular differentiation and polarization. To clarify CCDC85C function, we previously established Ccdc85c knockout (KO) rats. Our previous studies reported that CCDC85C is expressed during the kidney development and that its expression gradually decreases as maturation. The finding implies that CCDC85C is involved in kidney development. However, CCDC85C localization and the detailed kidney histology of Ccdc85c KO animals remain unclear. In the present study, we examined the expression patterns of CCDC85C and the histological consequences of Ccdc85c KO rat kidneys. Immunofluorescence revealed that CCDC85C was expressed in glomeruli at 4, 25 and 50 weeks of age, and distal renal tubules at 4 weeks of age. CCDC85C consistently co-localized with a tight junction marker, zonula occludens-1 (ZO-1) in the podocytes at 4, 25, and 50 weeks of age. At 4 weeks of age, Ccdc85c KO rats showed a thin renal cortex, small and variable size of glomeruli, flattened podocytes and indistinct slit diaphragms. These immature histological features suggest developmental retardation (hypoplasia). In conclusion, CCDC85C is expressed in glomeruli with its presence persisting into late adulthood in rats. The specific localization of CCDC85C suggests its involvement in the tight junction compartment of podocyte foot processes, where it likely maintains the filtration barrier. We propose that CCDC85C is important for the proper development and structural maintenance of the rat kidney.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148826212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genome-wide identification of genetic modifiers of Pak1-dependent skin tumor susceptibility in mice. pak1依赖性小鼠皮肤肿瘤易感性基因修饰因子的全基因组鉴定。

IF 2 4区农林科学

Experimental Animals Pub Date : 2026-08-21 DOI: 10.1538/expanim.26-0106

Kazuhiro Okumura, Megumi Saito, Keisuke Otoyama, Sora Tanaka, Kimi Araki, Yuichi Wakabayashi

{"title":"Genome-wide identification of genetic modifiers of Pak1-dependent skin tumor susceptibility in mice.","authors":"Kazuhiro Okumura, Megumi Saito, Keisuke Otoyama, Sora Tanaka, Kimi Araki, Yuichi Wakabayashi","doi":"10.1538/expanim.26-0106","DOIUrl":"https://doi.org/10.1538/expanim.26-0106","url":null,"abstract":"Pak1, a serine/threonine kinase, plays dual roles during the tumor progression and immune response. Unfortunately, the genetic modifiers underlying the resistance caused by Pak1 deficiency in CD11c-positive immune cells have been poorly defined so far. To adequately address this gap, we conducted a forward genetic screen using Cd11cCre-Pak1fl/+ F1 backcross mice (n=182). GRAS-Di-based genome-wide genotyping has identified 14,053 high-confidence markers, and we analyzed them by taking advantage of the principal component-adjusted generalized linear models (GLMs). Among the nine candidates of genome-wide significant Pak1 modifier loci (Pm1-Pm9) associated with tumor susceptibility, Pm1 on chromosome 5 showed the earliest and strongest association with the stages of papilloma and carcinoma. Intriguingly, epistasis analysis revealed that Pm3 on chromosome 4 attenuates the tumor-promoting effect of Pm1 in an allele-dependent manner, raising a possibility that the immune regulators modulate tumor susceptibility in Pak1-reduced immune compartment. Taken together, our present findings delineate a genetic framework implicated in Pm1/Pm3 axis during Pak1-reduced, skin carcinogenesis driven by immune response.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cordycepin inhibits the progression of liver cancer by suppressing the YAP/TAZ pathway. 虫草素通过抑制YAP/TAZ通路抑制肝癌的进展。

IF 2 4区农林科学

Experimental Animals Pub Date : 2026-08-20 DOI: 10.1538/expanim.26-0075

Weiting Li, Anyong Zhang, Rongfeng Song, Zhibin Liu, Songhua Wang, Li-Hua Yao, Wei Jiang

引用次数: 0

Diagnostic utility of a human N-terminal proANP assay for cardiac assessment in cynomolgus monkeys. 人类n端proANP测定在食蟹猴心脏评估中的诊断效用。

IF 2 4区农林科学

Experimental Animals Pub Date : 2026-08-19 DOI: 10.1538/expanim.26-0071

Shunya Nakayama, Ibuki Yoneda, Yuto Sawada, Takanobu Shimizu, Masao Akashi, Yasuyo Ito-Fujishiro, Tadashi Sankai, Yasuhiro Yasutomi, Hiroshi Koie, Naohide Ageyama

{"title":"Diagnostic utility of a human N-terminal proANP assay for cardiac assessment in cynomolgus monkeys.","authors":"Shunya Nakayama, Ibuki Yoneda, Yuto Sawada, Takanobu Shimizu, Masao Akashi, Yasuyo Ito-Fujishiro, Tadashi Sankai, Yasuhiro Yasutomi, Hiroshi Koie, Naohide Ageyama","doi":"10.1538/expanim.26-0071","DOIUrl":"https://doi.org/10.1538/expanim.26-0071","url":null,"abstract":"Atrial natriuretic peptide (ANP) is a well-established biomarker of cardiac disease; however, its clinical utility in cynomolgus monkeys is limited by its short half-life and the requirement for immediate proteolysis inhibition. This study validated a human NT-proANP assay in cynomolgus monkeys to facilitate the use of archived samples for cardiac assessment. We performed in silico amino acid sequence homology analysis and validated the assay using monkey serum and plasma. Stability under various storage conditions was also evaluated. The amino acid sequence of NT-proANP showed high conservation between humans and cynomolgus monkeys. The human NT-proANP assay demonstrated good cross-reactivity and a significant positive correlation with mature ANP levels (R2=0.60). Furthermore, NT-proANP remained detectable for up to 6 h post-collection at room temperature, although a gradual decline was observed. These findings indicate that NT-proANP is a highly useful surrogate marker for ANP in cynomolgus monkeys. This validation expands the potential for retrospective analysis using stored samples, thereby enhancing the value of non-human primate models in cardiovascular research.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Generation of mutant human SOD1 knock-in mouse lines at the Rosa26 locus as a platform for developing genome-editing therapies for amyotrophic lateral sclerosis. 在Rosa26位点产生突变的人类SOD1敲入小鼠系，作为开发肌萎缩性侧索硬化症基因组编辑疗法的平台。

IF 2 4区农林科学

Experimental Animals Pub Date : 2026-08-08 DOI: 10.1538/expanim.26-0040

Taro Okunomiya, Tomoki Sakasai, Kayoko Tsukita, Rina Shimizu, Aya Okusa, Masahiro Adachi, Saki Tomita, Akito Tanaka, Takayuki Kondo, Keiko Imamura, Haruhisa Inoue

{"title":"Generation of mutant human SOD1 knock-in mouse lines at the Rosa26 locus as a platform for developing genome-editing therapies for amyotrophic lateral sclerosis.","authors":"Taro Okunomiya, Tomoki Sakasai, Kayoko Tsukita, Rina Shimizu, Aya Okusa, Masahiro Adachi, Saki Tomita, Akito Tanaka, Takayuki Kondo, Keiko Imamura, Haruhisa Inoue","doi":"10.1538/expanim.26-0040","DOIUrl":"https://doi.org/10.1538/expanim.26-0040","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the degeneration of upper and lower motor neurons, resulting in progressive paralysis and death within a few years of symptom onset. Although current treatments modestly slow the disease progression, effective disease-modifying and curative therapies remain an urgent unmet need. SOD1 mutations are one of the major genetic causes of familial ALS. The p.Leu127Ser (L126S) and p.Gly94Ser (G93S) variants are clinically relevant pathogenic variants for which appropriate animal models are needed for preclinical evaluation of gene-editing therapies. However, most existing SOD1 models rely on high copy overexpression of mutant SOD1. Therefore, animal models carrying a single copy mutant human SOD1 allele are required for evaluating the in vivo efficacy of genome editing therapies. Here, we used CRISPR/Cas9-mediated homology-directed repair to generate a knock-in mouse line at the Gt(ROSA)26Sor (Rosa26) locus carrying a single-copy, 11-kb human SOD1 genomic fragment, including all exons and introns, with the L126S mutation. The Rosa26-hSOD1L126S mice did not develop ALS-like phenotypes during the limited observation period. However, they faithfully retained a single-copy mutant human SOD1 genomic allele, providing a valuable preclinical platform for evaluating genome-editing therapies. We also generated Rosa26-hSOD1G93S mice carrying the SOD1 G93S mutation with comparable efficiency. Together, these mutant human SOD1 knock-in mouse lines provide a versatile and clinically relevant platform for the preclinical evaluation of genome-editing therapies targeting heterozygous SOD1 mutations.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gasdermin E deficiency ameliorates caerulein/lipopolysaccharide -induced severe acute pancreatitis and systemic inflammation in mice. 气真皮蛋白E缺乏可改善蛋白/脂多糖诱导的小鼠严重急性胰腺炎和全身炎症。

IF 2 4区农林科学

Experimental Animals Pub Date : 2026-08-05 DOI: 10.1538/expanim.26-0022

Zhi-Jun Li, Lei Li, Ye-Ye Dai

{"title":"Gasdermin E deficiency ameliorates caerulein/lipopolysaccharide -induced severe acute pancreatitis and systemic inflammation in mice.","authors":"Zhi-Jun Li, Lei Li, Ye-Ye Dai","doi":"10.1538/expanim.26-0022","DOIUrl":"https://doi.org/10.1538/expanim.26-0022","url":null,"abstract":"This study investigated whether gasdermin E (GSDME) deficiency attenuates caerulein/lipopolysaccharide (LPS)-induced severe acute pancreatitis (SAP) in mice. Wild-type (WT) and Gsdme-knockout (KO) mice were assigned to PBS or caerulein/LPS groups. SAP was induced by repeated intraperitoneal caerulein injections for 2 consecutive days followed by a single LPS injection. Pancreatic injury was assessed by body weight change, pancreas-to-body weight ratio, serum amylase and lipase, and histopathology. Inflammatory responses were evaluated by serum cytokines, serum and pancreatic IL-33, HMGB1 subcellular distribution, and MPO/F4/80 immunohistochemistry. Cell death and gasdermin pathway activation were assessed by TUNEL staining and Western blotting. Compared with WT mice subjected to caerulein/LPS challenge, Gsdme-deficient mice showed less body weight loss, lower histopathological scores, and attenuated systemic inflammatory responses. Serum and pancreatic IL-33 levels, HMGB1 nuclear-to-cytoplasmic translocation, and circulating HMGB1 were also reduced in KO mice. Consistently, pancreatic MPO- and F4/80-positive inflammatory cell infiltration, TUNEL positivity, and the cleaved caspase-3/total caspase-3 ratio were reduced in KO mice. Cleaved and full-length GSDME were absent in KO pancreatic tissues, whereas caerulein/LPS treatment increased cleaved GSDME levels in WT mice. The cleaved caspase-1/total caspase-1 ratio and cleaved GSDMD expression increased after caerulein/LPS challenge in both genotypes, but neither was further elevated in KO mice, indicating no detectable compensatory upregulation of the canonical caspase-1/GSDMD pathway at the examined time point. Collectively, Gsdme deficiency alleviated caerulein/LPS-induced pancreatic injury and systemic inflammation, indicating that the caspase-3/GSDME axis contributes importantly, but not exclusively, to experimental SAP.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0