{"doi":"10.1166/jnn.2020.16416","title":"The Role of Janus Kinase/Signal Transducer and Activator of Transcription Signalling on Preventing Intestinal Ischemia/Reperfusion Injury with Dexmedetomidine","abstract":"<jats:p>Dexmedetomidine (Dex) works as a crucial agent for the treatment of intestinal ischemia/reperfusion (I/R), but its mechanism remains unclear. Recent articles demonstrated the pivotal role of Janus kinase/signal transducer and activator of transcription (JAK2/STAT3) signalling in I/R.\n Therefore, it is reasonable to explore the associated mechanism of JAK2/STAT3 signalling in Dex treatment. The study purpose was to evaluate the JAK2/STAT3 signalling regulatory mechanisms of Dex in preventing I/R. Anaesthetized rats were subjected to superior mesenteric artery occlusion consisting\n of 1 h of ischemia and 2 h of reperfusion while served as controls. Animals received subcutaneous administration of 50 <jats:italic>μ</jats:italic>g/kg Dex, JAK1 and JAK2 inhibitor, Ruxolitinib, selective JAK2 inhibitor, 10 mg/kg AG490 or STAT inhibitor and 0.4 mg/kg rapamycin; or Dex-treatment in the presence\n of <jats:italic>α</jats:italic>2-adrenoceptor antagonists Atip or Dex-treatment alone after I/R. Injury was scored histologically, apoptosis was detected via the apoptotic mediators caspase-3 and Bcl-2/Bax and the degree of activation of the JAK/STAT pathway was evaluated. Dex inhibited I/R injury by decreasing\n apoptosis significantly with rescue of cleaved caspase-3 and the Bcl-2/Bax ratio. Furthermore, phosphorylation of JAK2, STAT1 and STAT3 was affected, suggesting the involvement of activated JAK/STAT in response to Dex. Meanwhile, the JAK2 or STAT inhibitors AG490 and rapamycin, but not Ruxolitinib,\n exhibited a similar but even greater JAK2 and STAT3 regulatory effect, thus leading to a greater benefit. JAK2/STAT3 activation is crucial to the diminishing effect of Dex on mesenteric I/R injury; however, the efficacy and timing of Dex administration should be considered in clinical practice.</jats:p>","journal":"Journal of Nanoscience and Nanotechnology","year":2020,"id":632951,"datarank":0.4887144807032224,"base_score":3.258096538021482,"endowment":3.258096538021482,"self_citation_contribution":0.4887144807032224,"citation_network_contribution":0.0,"self_endowment_contribution":0.4887144807032224,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1107576,"name":"Jun Zhou","orcid":"0000-0003-4799-8165","position":1,"is_corresponding":false},{"id":253961,"name":"Qian Hu","orcid":"0000-0002-5783-7085","position":2,"is_corresponding":false},{"id":1640860,"name":"Zhengren Liu","orcid":null,"position":3,"is_corresponding":false},{"id":1640861,"name":"Qiuhong Chen","orcid":null,"position":4,"is_corresponding":false},{"id":1253759,"name":"Wenxiang Wang","orcid":"0000-0002-4679-3216","position":5,"is_corresponding":false},{"id":1640862,"name":"Huaigen Zhang","orcid":null,"position":6,"is_corresponding":false},{"id":396791,"name":"Qin Zhang","orcid":"0000-0002-1023-480X","position":7,"is_corresponding":false},{"id":1640863,"name":"Yuanlu Huang","orcid":null,"position":8,"is_corresponding":false},{"id":1640859,"name":"Xuekang Zhang","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The Role of Janus Kinase/Signal Transducer and Activator of Transcription Signalling on Preventing Intestinal Ischemia/Reperfusion Injury with Dexmedetomidine","abstract":"<jats:p>Dexmedetomidine (Dex) works as a crucial agent for the treatment of intestinal ischemia/reperfusion (I/R), but its mechanism remains unclear. Recent articles demonstrated the pivotal role of Janus kinase/signal transducer and activator of transcription (JAK2/STAT3) signalling in I/R.\n Therefore, it is reasonable to explore the associated mechanism of JAK2/STAT3 signalling in Dex treatment. The study purpose was to evaluate the JAK2/STAT3 signalling regulatory mechanisms of Dex in preventing I/R. Anaesthetized rats were subjected to superior mesenteric artery occlusion consisting\n of 1 h of ischemia and 2 h of reperfusion while served as controls. Animals received subcutaneous administration of 50 <jats:italic>μ</jats:italic>g/kg Dex, JAK1 and JAK2 inhibitor, Ruxolitinib, selective JAK2 inhibitor, 10 mg/kg AG490 or STAT inhibitor and 0.4 mg/kg rapamycin; or Dex-treatment in the presence\n of <jats:italic>α</jats:italic>2-adrenoceptor antagonists Atip or Dex-treatment alone after I/R. Injury was scored histologically, apoptosis was detected via the apoptotic mediators caspase-3 and Bcl-2/Bax and the degree of activation of the JAK/STAT pathway was evaluated. Dex inhibited I/R injury by decreasing\n apoptosis significantly with rescue of cleaved caspase-3 and the Bcl-2/Bax ratio. Furthermore, phosphorylation of JAK2, STAT1 and STAT3 was affected, suggesting the involvement of activated JAK/STAT in response to Dex. Meanwhile, the JAK2 or STAT inhibitors AG490 and rapamycin, but not Ruxolitinib,\n exhibited a similar but even greater JAK2 and STAT3 regulatory effect, thus leading to a greater benefit. JAK2/STAT3 activation is crucial to the diminishing effect of Dex on mesenteric I/R injury; however, the efficacy and timing of Dex administration should be considered in clinical practice.</jats:p>","is_dataset_classified":null,"base_score":3.258096538021482,"endowment":3.258096538021482,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"31635678","pmcid":null,"openalex_id":"https://openalex.org/W2982345079","authors":[],"funders":[],"total_grants":0,"fwci":3.2957,"citation_percentile":0.92452032,"influential_citations":0,"citation_trend":[{"year":2020,"count":3},{"year":2021,"count":4},{"year":2022,"count":5},{"year":2023,"count":5},{"year":2024,"count":4},{"year":2025,"count":1},{"year":2026,"count":3}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://www.ingentaconnect.com/content/asp/jnn/2020/00000020/00000005/art00080","host_type":"publisher"},{"url":"https://doi.org/10.1166/jnn.2020.16416","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/31635678","host_type":"repository"}],"fields_of_study":["Anesthesia and Sedative Agents","Anesthesia and Neurotoxicity Research","Cardiac Ischemia and Reperfusion","Animals","Apoptosis","Dexmedetomidine","Janus Kinase 2","Rats","Reperfusion Injury","STAT3 Transcription Factor","Signal Transduction"],"mesh_terms":["Animals","Signal Transduction","Reperfusion Injury","Apoptosis","Dexmedetomidine","STAT3 Transcription Factor","Rats","Janus Kinase 2"],"keywords":["STAT protein","STAT3","Janus kinase","STAT1","JAK-STAT signaling pathway","Janus kinase 2","Pharmacology","stat","Apoptosis","Medicine","Activator (genetics)","Reperfusion injury","Phosphorylation","Signal transduction","Ischemia","Chemistry","Biology","Internal medicine","Cell biology","Receptor","Biochemistry"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T10:38:12.753546Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}